No full-text available
To read the full-text of this research,
you can request a copy directly from the authors.
Antiobesity effect of flaxseed polysaccharide via inducing satiety due to leptin resistance removal and promoting lipid metabolism through the AMPK signaling pathway
Abstract
Obesity is a metabolic syndrome worldwide that causes many chronic diseases. Recently, we found an antiobesity effect of flaxseed polysaccharide (FP), but the mechanism remains to be elucidated. In this study, rats were first developed to obesity by feeding high-fat diet. The obese rats were then fed a control diet AIN-93M (Group HFD) and 10% FP diet (Group FPD). The body weight, body fat, adipose tissue and liver sections, serous total triglycerides, the levels of fasting blood glucose in serum, serous insulin, inflammatory cytokines in serum, serous proteins within the leptin-neuropeptide Y (NPY) and AMPK signaling pathway were analyzed and determined. FP intervention significantly reduced body weight and abdominal fat from 530 ± 16 g and 2.15 ± 0.30% in Group HFD to 478 ± 10 g and 1.38± 0.48% in Group FPD, respectively. This effect was achieved by removing leptin resistance possibly by inhibiting inflammation and recovering satiety through the significant downregulation of NPY and the upregulation of glucagon-like peptide 1. Adiponectin was then significantly upregulated probably via the gut-brain axis and further activated the AMPK signaling pathway to improve lipid metabolism including the improvement of lipolysis and fatty acid oxidation and the suppression of lipogenesis. This is the first report of the proposed antiobesity mechanism of FP, thereby providing a comprehensive understanding of nonstarch polysaccharides and obesity.
... FP is a heteropolysaccharide composed of acidic and neutral components [9]. In our previous research, we found that FP has an anti-obesity effect via promoting lipid Foods 2022, 11,1991 2 of 14 metabolism, inducing satiety, and regulating the intestinal flora [12,13]. As a polysaccharide, FP cannot be digested and absorbed directly as nutrients by the body to play a role, so the obesity-inhibiting FP pathway is still unclear. ...
... As shown in our previous research [13], eighteen male Sprague-Dawley (SPF grade) rats, 4 weeks old, were bought from Guangdong Medical Laboratory Animal Center (Guangzhou China). After 10 days of adaptive feeding with a standard diet (D12450B), the rats were randomly divided into two groups, namely the control group (Group Con, n = 6) and the obesity group (n = 12), to establish the obesity model. ...
... Thus, the upregulation of Lpl might inhibit the release of chylomicrons and the rise of plasma TG levels. In our previous study, it was found that the serum TG level of FP-fed rats was significantly lower than that of obese rats [13], which is consistent with our current inference. ...
Obesity is one of the most serious public health challenges. Recently, we found that flaxseed polysaccharides (FPs) had an anti-obesity effect through promoting lipid metabolism, but the obesity-inhibiting pathway of FP is still unclear. In this study, after FP intervention in an obese rat model, a transcriptome study was performed to further investigate how FP intervention alters the gene expression of colonic epithelial tissues (CETs). The results showed that there were 3785 genes differentially expressed due to the FP intervention, namely 374 downregulated and 3411 upregulated genes. After analyzing all the differentially expressed genes, two classical KEGG pathways were found to be related to obesity, namely the PPAR-signaling pathway and energy metabolism, involving genes Fabp1–5, Lpl, Gyk, Qqp7, Pparg, Rxrg, Acsl1, Acsl4, Acsl6, Cpt1c, Car1–4, Ca5b, Car8, Car12–14, Cps1, Ndufa4l2, Cox6b2, Atp6v1g2, Ndufa4l2 and Cox4i2. QRT-PCR results showed a consistent expression trend. Our results indicate that FP promotes lipid metabolism by changing the expression of some key genes of CETs, thus inhibiting obesity.
... AMPK modulates hepatic lipid metabolism via the stimulation of fatty acid oxidation and inhibition of lipogenesis and glucose synthesis. 32 For instance, AMPK controls the fat pro- Fig. 7 Associations of gut microbial composition with obesity-related indices. The asterisk (*) indicates the statistical significance for the correlations between phenotypes and the relative abundances of the genus. ...
... This journal is © The Royal Society of Chemistry 2021 duction pathway by suppressing the nuclear translocation of SREBP-1c, which can regulate gene expression of FAS and ACCα in lipogenesis. 32 Since SREBP-1c was downregulated, ACC and FAS were suppressed, which resulted in the inhibition of fatty acid synthesis. 33,34 SCF significantly upregulated the expression of p-AMPK and AMPK, and downregulated lipogenesis-related SREBP-1c, FAS and ACCα expression. ...
The aim of this study was to investigate the effects of Smilax china L. flavonoid (SCF) on obesity and changes in gut microbiota high-fat/high-sucrose (HFHS)-fed mice. Male C57BL/6 mice fed either a normal-chow (NC) or a HFHS diet were treated with SCF for 12 weeks. The effect of SCF on the composition of gut microbiota was assessed by 16S rDNA sequencing. SCFA levels in the caecum were quantified by GC-MS. SCF supplementation alleviated the body weight gain, fat accumulation, serum lipid parameters, and hepatic steatosis and improved glucose homeostasis. SCF significantly increased plasma adiponectin level, adiponectin-receptor-gene (AdipoR1 and AdipoR2) expression in the liver, activated AMPKα, downregulated the expression of SREBP1-c, FAS, and ACCα, and upregulated the expression of PPARα, CPT-1α, and UCP-1. The anti-obesity effects of SCF might be through upregulation of adiponectin-receptor/AMPK signalling to improve lipid metabolism. SCF reversed HFHS-induced dysbiosis of gut microbiota and decreased SCFA production in the caecum, thus reducing energy absorption and leading to loss of body weight. Spearman's correlation analysis revealed significant correlations between obesity phenotypes, SCFA levels, and changes in gut microbiota. The results showed that SCF may be an effective dietary supplement that is useful for suppressing the development of obesity and associated disorders.
... Among these functions, the lipid-lowering effect of polysaccharides has become a focus of research in recent years. Polysaccharides from soybean (11), flaxseed (12) and Momordica charantia (13) ...
... The molecular mechanisms by which PSP prevents HFD-induced obesity. The liver is one of the key organs involved in lipid regulation (12). In this present study, mouse livers were collected to explore the potential signaling pathways of PSP in HFD-induced hepatic steatosis. ...
The present study sought to elucidate the role of Polygonatum sibiricum F. Delaroche polysaccharide (PSP) in high‑fat diet (HFD)‑induced mouse obesity and investigated the primary molecular mechanism underlaying these effects. An obese mouse model was established by feeding HFD and three doses of PSP were administered intragastrically. Changes in body weight, serum lipids and parameters were recorded and the mechanism was explored by reverse transcription‑quantitative PCR and western blotting. Body weight, blood lipids, blood glucose, insulin, resistin, adiponectin, liver weight and abdominal fat pads weight were reduced by PSP and abnormal expression levels of inflammatory factors such as TNF‑α, IL‑6, IL‑1β and iNOS and lipid metabolism genes such as FAS, SREBP‑1, PPARα and CPT‑1were also reversed by PSP. The 5' adenosine monophosphate‑activated protein kinase (AMPK) signaling pathway was activated in PSP mouse liver, leading to lipid‑lowering and anti‑inflammatory effects. The results therefore suggested that PSP exhibited lipid‑lowering and anti‑inflammatory effects by activating the AMPK signaling pathway.
... NDPs like konjac glucomannans [10], b-glucan [11] have been approved as food supplements for many years. Accumulating evidence has shown that they could prevent the development of obesity through a variety of mechanisms such as regulating lipids metabolism [12,13], reducing inflammation level [14][15][16], improving insulin resistance [17,18], and so on. The way that NDPs with relatively low bioavailability exert their anti-obesogenic activities in the body, such as changing the body composition, improving disordered metabolism are likely to be based on their behavior in the Gastrointestinal (GI) system to large extent. ...
... NDPs can regulate the secretion of GI hormones such as GLP-1, PYY, Cholecystokinin (CCK) and ghrelin to control the uptake of food. A recent study found that a NDP from flaxseed contributed to satiety through up-regulation of GLP-1, which might further increase the level of adiponectin and promote lipid metabolism via AMP-Activated Protein Kinase (AMPK) regulation [13]. Several studies also have demonstrated that NDPs intake is positively associated with the level of PYY [103,104] and CCK [105]. ...
Nowadays, obesity in humans is a huge challenge requiring effective, readily available, and low-risk alternative treatments. Intake of edible Non-Digestible Polysaccharides (NDPs) is regarded as a promising strategy to combat obesity. Herein, an overview of the behavior of NDPs in the Gastrointestinal (GI) tract and its association with anti-obesity effect is summarized. Both the in vitro and in vivo of such investigations are discussed. Results show that NDPs can reach the large intestine to mediate the gut microbiota with the extent of regulation varies among NDPs with different chemical structures. The possible anti-obesity mechanisms associated with behavior of NDPs in the GI tract include: (i) inhibition of fat absorption, (ii) modification of gut microbiota and their metabolites such as short-chain fatty acids, (iii) regulation of bile acid profiles, (iv) modulation on appetite and satiety effect, and (v) protection of intestinal barrier. However, more efforts are required to clarify the exact behavior and their beneficial effects of NDPs within GI tract. This paper will provide an overlook of recent advances for better understanding anti-obesity activity of NDPs.
•An overview of in vitro and in vivo studies on the behavior of edible Non-Digestible Polysaccharides (NDPs) in the Gastrointestinal (GI) tract is presented.
•The anti-obesity mechanisms of NDPs based on their GI behavior are discussed.
... Although multiple phytochemicals have been reported to possess the potential capability of regulating fat accumulation and distribution, their specific efficacy and the underlying molecular mechanism remain controversial. [7][8][9][10] Flavonoids are a class of polyphenols present in foods possessing anti-inflammatory, anticancer, and antiviral activities. [11][12][13] According to the different molecular structures, flavonoids are mainly classified into flavones, flavanones, cate-chins, and anthocyanins. ...
As a natural pigment in food, quercetin possesses multiple biological activities and plays a crucial role in regulating metabolic syndrome. Herein, we aim to explore the potential mechanism of quercetin to ameliorate hepatic fat accumulation. In vivo experiments showed that quercetin significantly relieved inflammation response by decreasing the serum TNF-α and IL-6 levels and also improved high-fat diet-induced hepatic steatosis without other organ injuries. Quercetin can effectively reduce lipid aggregation and down-regulate the protein expression of PCK1 in HepG2 cells induced by oleic acid and palmitic acid, indicating that inhibiting gluconeogenesis leads to hepatic fat accumulation reduction. Furthermore, molecular docking results suggested that quercetin can bind to both PPARα and PPARγ, with an even more potent binding affinity than indeglitazar, a pan-agonist of PPARs. In conclusion, quercetin may regulate gluconeogenesis to ameliorate hepatic fat accumulation via targeting PPARα/γ.
... When combined with the high fiber content of nonsoy legumes, this characteristic lowers the GI, which may explain the beneficial effects on glucose control indicators [82]. Furthermore, because of their high fiber and protein content, as well as their low GI, nonsoy legumes may help people lose weight by increasing satiety [83] through various mechanisms [84]. Increased intraluminal viscosity reduces gastric emptying and macronutrient absorption by slowing digestion and increasing gastric distention caused by chewing effort; by influencing gut hormone secretion; and producing SCFAs (propionate, butyrate, and acetate) derived from the fermentation of fiber by colonic bacteria, which slows digestion and increases gastric distention. ...
There is an equivocal and inconsistent association between legume consumption and health outcomes and longevity. The purpose of this study was to examine and quantify the potential dose–response relationship between legume consumption and all-cause and cause-specific mortality in the general population. We conducted a systematic literature search on PubMed/Medline, Scopus, ISI Web of Science, and Embase from inception to September 2022, as well as reference lists of relevant original papers and key journals. The random-effects model was used to calculate the summary HRs and their 95% CIs for the highest and lowest categories, as well as for a 50 g/d increment. We also modeled curvilinear associations using a 1-stage linear mixed-effects meta-analysis. Thirty-two cohorts (31 publications) involving 1,141,793 participants and 93,373 deaths from all causes were included. Higher intakes of legumes, compared with lower intakes, were associated with a reduced risk of mortality from all causes (HR: 0.94; 95% CI: 0.91, 0.98; n = 27) and stroke (HR: 0.91; 95% CI: 0.84, 0.99; n = 5). There was no significant association for CVD mortality (HR: 0.99; 95% CI: 0.91, 1.09; n =11), CHD mortality (HR: 0.93; 95% CI: 0.78, 1.09; n = 5), and cancer mortality (HR: 0.85; 95% CI: 0.72, 1.01; n = 5). In the linear dose–response analysis, a 50 g/d increase in legume intake was associated with a 6% reduction in the risk of all-cause mortality (HR: 0.94; 95% CI: 0.89, 0.99; n = 19), but no significant association was observed for the remaining outcomes. The certainty of evidence was judged from low to moderate. A higher legume intake was associated with lower mortality from all causes and stroke, but no association was observed for CVD, CHD, and cancer mortality. These results support dietary recommendations to increase the consumption of legumes.
... The beneficial immune-modulatory effects of Lactobacillus are stimulated through several molecules, such as peptidoglycan and exopolysaccharides, which interact with specific host cell receptors (TLR-2 and TLR-4) [77]. AMPK is an important upstream gene that regulates the balance of lipid metabolism by inhibiting fatty acid and cholesterol synthesis [78]. Activation of AMPK can inhibit the production of TNF-α and IL-6 [79]. ...
Hyperlipidemia is a leading cause of atherosclerosis and coronary heart disease (CHD). This study aimed to investigate the hypolipidemic effect of Lactobacillus casei ATCC 7469-fermented wheat bran extract and Spirulina maxima extract on Sprague–Dawley rats fed a regular or high-fat diet compared to rosuvastatin as a reference drug. Treatment with Lactobacillus casei ATCC 7469-fermented wheat bran and Spirulina maxima resulted in a significant decrease in total cholesterol (TC), triglycerides (TG.), low-density lipoprotein (LDL) and very low-density lipoprotein (VLDL) (p < 0.05) and a significant increase in high-density lipoprotein (HDL) (p < 0.05). That combination also improved liver functions. It also resulted in the improvement of liver oxidative biomarkers and decreased the production of inflammatory markers (TNF-α, IFN-γ, IL-10, and IL-1β). In addition, a significant reduction in inflammation of liver tissues was observed after that treatment. Lactobacillus casei ATCC 7469-fermented wheat bran extract and Spirulina maxima extract had additive effects on the lipid profile, liver functions and immune system of rats similar to rosuvastatin.
... In the present study, the observed activation of SREBP-1c and FABP-4 levels may be beneficial in significant uptake of circulatory fatty acid ends with reduced hyperlipidemia and metabolic inflammation. In this context, Luo et al. [42] have found a mechanistic anti-obesity effect of flaxseed polysaccharide via inducing satiety by leptin resistance and promoting lipid metabolism through the AMPK signaling pathway. Berndt et al. [43] reported that impaired insulin sensitivity was associated with decreased adipose triglyceride lipase (ATGL) and HSL expression, independently of body fat mass and fat distribution. ...
Excessive storage of lipids in visceral or ectopic sites stimulates adipokine production, which attracts macrophages. This process determines the pro- and anti-inflammatory response regulation in adipose tissue during obesity-associated systemic inflammation. The present study aimed to identify the composition of Ocimum basilicum L. (basil) seed extract and to determine its bio-efficacy on adipocyte thermogenesis or fatty acid oxidation and inhibition of lipid accumulation and adipokine secretion. Ocimum basilicum L. seed methanol extract (BSME) was utilized to analyze the cytotoxicity vs. control; lipid accumulation assay (oil red O and Nile red staining), adipogenesis and mitochondrial-thermogenesis-related gene expression vs. vehicle control were analyzed by PCR assay. In addition, vehicle control and BSME-treated adipocytes condition media were collected and treated with lipopolysaccharide (LPS)-induced macrophage to identify the macrophage polarization. The results shown that the active components present in BSME did not produce significant cytotoxicity in preadipocytes or macrophages in the MTT assay. Furthermore, oil red O and Nile red staining assay confirmed that 80 and 160 μg/dL concentrations of BSME effectively arrested lipid accumulation and inhibited adipocyte maturation, when compared with tea polyphenols. Gene expression level of adipocyte hyperplasia (CEBPα, PPARγ) and lipogenesis (LPL)-related genes have been significantly (p ≤ 0.05) downregulated, and mitochondrial-thermogenesis-associated genes (PPARγc1α, UCP-1, prdm16) have been significantly (p ≤ 0.001) upregulated. The BSME-treated, maturing, adipocyte-secreted proteins were detected with a decreased protein level of leptin, TNF-α, IL-6 and STAT-6, which are associated with insulin resistance and macrophage recruitment. The “LPS-stimulated macrophage” treated with “BSME-treated adipocytes condition media”, shown with significant (p ≤ 0.001) decrease in metabolic-inflammation-related proteins—such as PGE-2, MCP-1, TNF-α and NF-κB—were majorly associated with the development of foam cell formation and progression of atherosclerotic lesion. The present findings concluded that the availability of active principles in basil seed effectively inhibit adipocyte hypertrophy, macrophage polarization, and the inflammation associated with insulin resistance and thrombosis development. Ocimum basilicum L. seed may be useful as a dietary supplement to enhance fatty acid oxidation, which aids in overcoming metabolic complications.
... Leptin, which is encoded by LEP gene, is considered to be the first discovered adipokine [20]. Leptin is a critical factor in signal transduction such as AMPK [21,22], PI3K/ AKT [23], ERK1/2 [24], and STAT3 [25]. In turn, leptin participates in controlling energy balance [26], metabolism [27], immune [28], tumorigenesis [29], and cancer metastasis [30]. ...
Tumor-associated macrophage (TAM) is a major component of tumor microenvironment (TME) and plays critical role in the progression of cancer metastasis. However, TAM-mediated regulation in gallbladder cancer (GBC) has not been fully characterized. Here, we found that exosomes derived from GBC cell polarized macrophage to M2 phenotype, which then facilitated the invasion and migration of GBC cells. We discovered that leptin was enriched in GBC cell-derived exosomes. Exosomal leptin levels promoted invasion and migration of GBC-SD cells. The inhibition of leptin not only attenuated M2 macrophage of polarization but also inhibited the invasive and migratory ability of GBC cell. In addition, GBC-SD cell-derived exosomal leptin induced M2 polarization of macrophage via activation of STAT3 signal pathway. Taken together, our results suggested that GBC cells secrete exosome-enclosed leptin facilitated cell invasion and migration via polarizing TAM.
... AMPK is an important upstream gene that regulates the balance of lipid metabolism [32]. AMPK can inhibit fatty acid and cholesterol synthesis and promote fatty acid oxidation [33]. L. rhamnosus JL1 can reactivate the expression of AMPK and restore the balance of lipid metabolism. ...
Probiotics can prevent obesity and related metabolic complications. In our study, the protective effect and molecular mechanism of Lactobacillus rhamnosus JL1 (separated from the feces of healthy infants) on high-fat diet mice were investigated. After 10 weeks of dietary intervention with L. rhamnosus JL1 intervention, the body weight of the JL1 group (23.78 g) was significantly lower than that of the HFD group (26.59 g, p < 0.05) and the liver index was reduced. Serum biochemical analysis showed that the TC, TG and LDL-C contents of JL1 group mice were significantly decreased (p < 0.05). Histological images of the mice livers showed that the degree of lipid action and damage of hepatic cells were improved. L. rhamnosus JL1 activated the AMPK pathway, and reduced the gene expression of PPAR-γ, LXR-α and SREBP-1C. In addition, the protein expression of PPAR-γ and LXR-α were reduced. After dietary intervention with L. rhamnosus JL1, the concentration of acetic acid, propionic acid, and butyric acid were increased significantly, especially the concentration of butyric acid, which was 63.16% higher than that of the HFD group (p < 0.05). In conclusion, this study provided a theoretical reference for the development and application of probiotics derived from healthy infant feces in health products and functional foods.
... Many flaxseed components may have positive effects on weight management: lignans are reported to reduce visceral fat and increase fat oxidation and adiponectin levels in mice [278], but their supplementation alone was not shown to be effective in improving body composition in humans [277]; soluble fiber, which represent up to 27% of flaxseed weight, may induce a feeling of fullness, delay gastric emptying and increase SCFA concentration in the gut, inducing satiety and promoting weight loss via GI hormones release [279]. Furthermore, ALA has been shown to increase adipose leptin expression in animal models [280] and flaxseed polysaccharides have been able to induce satiety improving leptin resistance together with enhancing lipolysis and suppressing lipogenesis through the AMPK signaling pathway [281]. Lastly, ALA metabolism products, eicosapentaenoic acid and docosahexaenoic acid, were able to induce adipocytes apoptosis, suppress appetite and enhance fat oxidation and energy expenditure in animal models, while human studies confirmed its potential benefit only in combination with exercise and hypocaloric diets [282]. ...
The use of food supplements for weight loss purposes has rapidly gained popularity as the prevalence of obesity increases. Navigating through the vast, often low quality, literature available is challenging, as is providing informed advice to those asking for it. Herein, we provide a comprehensive literature revision focusing on most currently marketed dietary supplements claimed to favor weight loss, classifying them by their purported mechanism of action. We conclude by proposing a combination of supplements most supported by current evidence, that leverages all mechanisms of action possibly leading to a synergistic effect and greater weight loss in the foreseen absence of adverse events. Further studies will be needed to confirm the weight loss and metabolic improvement that may be obtained through the use of the proposed combination.
... In the previous research, we had found axseed polysaccharides (FP) had an anti-obesity effect via promoting lipid metabolism, inducing satiety and regulating the intestinal ora [9][10]. However, as a polysaccharide, FP can not directly enter the body to play a role, so we speculate that it can promote weight loss through the interaction with intestinal ora, change the gene expression of intestinal epithelial tissue, and induce the metabolism of fat and energy in vivo. ...
Background
Obesity is one of the most serious public health challenges. Recently, we found that flaxseed polysaccharide (FP) had an anti-obesity effect through promoting lipid metabolism, inducing satiety and regulating gut microbiota, but how FP promote lipid metabolism through altering the colonic epithelial cells remains to be elucidated. In this study, a transcriptome study was performed to investigate the effect of FP altering the gene expression of colonic epithelial cells in an obese rat model. ResultsThe transcriptome analysis showed that 3,785 genes were differentially expressed after FP intervention in colonic epithelial cells, including 374 down-regulated and 3,411 up-regulated genes. Through KEGG analysis, we found out three classical pathways related to lipid metabolism and energy metabolism, including PPAR signaling pathway, nitrogen metabolism and oxidative phosphorylation (OXPHOS). Moreover, qRT-PCR results showed consistent expression trends of differential genes with transcriptome analysis. Conclusions
The anti-obesity effect of FP may be achieved by regulating the expression of lipid metabolism- and energy metabolism-related proteins acting on the PPAR (peroxisome proliferator-activated receptor) signaling pathway, nitrogen metabolism and OXPHOS pathway in vivo .
... Multiple physiological functions of digestible flaxseed protein and its derived peptides have been documented, such as antihypertension, antioxidation, anti-inflammation, anti-diabetes, and antibiosis (Wu, Wang, Qi, & Guo, 2019). Soluble flaxseed polysaccharides, according to previous reports, are able to stimulate immune responses, inhibit hepatitis B virus, and prevent obesity (Liang et al., 2019;Luo et al., 2019). As to flaxseed lignans and their derivatives, various biological effects have been recorded, including antioxidation, cardiovascular benefits, anticancer, and antidiabetic effects (Lan et al., 2019). ...
... The rhamnose, galactose, and xylose were present in much higher levels than the other monosaccharides. In a previous study, the water-soluble polysaccharides isolated from flaxseed were shown to consist of 6-7 kinds of monosaccharides, including rhamnose, arabinose, fucose, xylose, mannose, glucose, galactose, and galacturonic acid (Luo et al., 2019). Most of these are similar to the monosaccharides we identified. ...
This study was conducted to investigate the effects and mechanism of quercetin on chicken quality in broilers. We selected 480 AA broilers (1 day old) and randomly allotted those to four treatments (negative control and 0.2, 0.4, or 0.6 g of quercetin per kg of diet) for 42 days. Compared with the control group, the supplementation with 0.4 g of quercetin significantly increased the pH45min and L* value of the thigh muscle and decreased the shearing force of the thigh muscle and breast muscle and drip loss of the thigh muscle (P < 0.05). The supplementation with 0.6 g/kg of quercetin significantly increased the pH45min and L* value of the thigh muscle, and pH45min of breast muscle and decreased the drip loss of the thigh muscle (P < 0.05). Sensory scores of meat color, tenderness, and juiciness also were improved with increasing quercetin concentration (P < 0.05). The inosinic acid (IMP) content of the breast and thigh muscles of broilers was significantly increased by supplementation with 0.6 g/kg of quercetin (P < 0.05). Supplementation with 0.2, 0.4, and 0.6 g of quercetin significantly reduced mRNA expression of L-FABP (P < 0.05, P < 0.05, and P < 0.05); supplementation with 0.4 and 0.6 g/kg of quercetin significantly increased mRNA expression of PKB and AMPKα1 (P < 0.05 and P < 0.05); supplementation with 0.6 g/kg of quercetin in the diet significantly reduced mRNA expression of SREBP1 and HMGR (P < 0.05 and P < 0.05) and significantly increased mRNA expression of CPT1 and PPARγ (P < 0.05 and P < 0.05); and supplementation with 0.2, 0.4, and 0.6 g/kg of quercetin significantly increased mRNA expression of PI3K, LPL, and Apo A1 and significantly reduced mRNA expression of ACC and FATP1 in the breast muscle of broilers (P > 0.05). PI3k, PKB, AMPK, SREBP1, and L-FABP were significantly and positively correlated with pH45min (P < 0.05); PPARγ was significantly and positively correlated with shear force (P < 0.05); CPT1 was significantly and positively correlated with the L* value (P < 0.05); and HMGR was significantly and positively correlated with drip loss (P < 0.05). In conclusion, quercetin improved the meat quality, protecting it against lipid oxidation and deposition by regulating the PI3K/PKB/AMPKα1 signaling pathway in the breast muscle of broilers.
Soybean soluble polysaccharide (SSPS) was reported to possess the anti-obesity activity and improve metabolic syndrome. Unfortunately, the underlying mechanisms are not well understood. Here, we treated high-fat diet (HFD) Sprague Dawley rats with 250 mg per kg of SSPS, the SSPS treatment significantly decreased their body weight (P < 0.001), liver index value (P < 0.01), as well as the concentration levels of Triglyceride (TG), total cholesterol (TC), low-density cholesterol (LDL-C)), and inflammatory cytokines in the serum. Furthermore, we uncovered 276 differently expressed proteins (P < 0.05) highly involved in lipid metabolism processes. Additionally, after SSPS treatment, both fatty acid binding protein 5 and 7 were downregulated, consistent with the in vivo results. However, peroxisome proliferator-activated receptor γ expression in liver tissue was up-regulated, contradictory to in vitro results. We deduced that two different lipid metabolism mechanisms exist between in vivo and in vitro. Furthermore, in the in vitro experiments, SSPS exerted a lipid-lowering effect. Altogether, the study's results provide an overview of SSPS-induced changes in the liver proteome, which could help us understand the molecular mechanism by which SSPS alleviates obesity.
The development of white adipose tissue (WAT) browning helps to protect animals from cold conditions and prevent obesity. AMPKα1 has been involved in the process of white adipocytes browning. Although Irisin plays a vital role in the browning of WAT, the detailed regulatory mechanism of Irisin inducing the browning of WAT remains unclear. Herein, we firstly investigated the potential roles of differentiation and Irisin in regulating the browning of 3 T3-L1 cells. The results found that they could significantly increase the number of lipid droplets and upregulate the expression levels of UCP1, PGC-1α, PRDM16, and p-AMPKα1. Then we proved the effectiveness of the AMPKα1 signaling pathway in the process of Irisin inducing the browning of 3 T3-L1 cells. Compared with si-NC, si-AMPKα1 not only decreased the number of Irisin-induced lipid droplets, but also attenuated the expression of Irisin-induced UCP1, PGC-1α, and PRDM16 protein and mRNA levels in 3 T3-L1 cells. Furthermore, the results showed that Irisin increased the positive distribution of UCP1 and PGC-1α, and upregulated the expression of UCP1, PGC-1α, and PRDM16 at both protein and mRNA levels in WAT. Once siRNA treated mice, the facilitation of Irisin on UCP1 and PGC-1α in si-AMPKα1-injected mice was lower than that in si-NC-injected mice. Compared with si-NC, si-AMPKα1 significantly downregulated the expression of UCP1, PGC-1α, and PRDM16 in Irisin-injected mice. Taken together, our results demonstrate that Irisin activates the AMPKα1 pathway to promote the browning of WAT by upregulating the mRNA and protein levels of UCP1, PGC-1α, and PRDM16.
A polysaccharide from jackfruit pulp (JFP-Ps) has been found to exhibit various types of bioactivities. This study aimed to investigate the effects and potential mechanisms of JFP-Ps on non-alcoholic fatty liver disease (NAFLD) induced by high-fat diet in rats. The pathological changes in the liver and liver function were determined using hematoxylin-eosin staining and biochemical analysis. RT-qPCR and Western blots were employed to study the expression of proteins associated with lipid metabolism and proinflammatory cytokines. Results showed that JFP-Ps reduced liver weight and liver index, and influenced liver function in high-fat diet rats. Furthermore, JFP-Ps up-regulated the lipolytic genes (PPARα, LPL, CPT1, HSL) expression, downregulated the expression of lipogenic genes (SREBP-1c, ACC, FAS) and proinflammatory cytokines (TNF-α, IL-6) genes. JFP-Ps increased the protein expression of p-AMPK, and decreased the protein expression of SREBP-1c and AMPK. These results revealed that JFP-Ps might improve liver function and alleviate NAFLD through activating PPAR and AMPK signaling pathways.
Recently, lipid metabolism disorder (LMD) has been regarded as a risk factor leading to multiple diseases and affecting human health. Procyanidins have been reported to be a potential therapy for LMD. This study explored the effect and possible mechanism of procyanidins from hawthorn (HPC) in LMD rats fed a high-fat diet. HPC supplementation for 8 weeks significantly relieved lipid accumulation in the serum and liver, and protected the structure of liver in LMD rats. The amelioration of insulin resistance, lipid metabolism related hormones and oxidative stress was also found. Moreover, HPC also regulated the structure of gut microbiota, especially increased the abundances of Akkermansia, Bacteroides and Adlercreutzia, and decreased Lactobacillus, Bifidobacterium, Blautia, Lachnospiraceae and Subdoligranulum. Additionally, HPC enriched genes were involved in the fatty acid biosynthesis, MAPK, and lipopolysaccharide biosynthesis pathways. We found a high LPS level due to the microbiome disorder induced by the high-fat diet, and then western blot results showed that HPC maintained the intestinal barrier and mitigated inflammation and lipid accumulation in the liver via regulating the NF-κB and AMPK pathways, which were related to LMD. This study provided new insights into dietary intervention based on HPC to alleviate LMD via stabilizing the gut-liver axis.
In this study, novel Poria cocos oligosaccharides (PCO) were prepared by enzymatic degradation, and their polymerization degree was determined to be 2-6 by LC-MS analysis. By monosaccharide composition analysis, methylation assay, FT-IR, and NMR analysis, PCO were deduced to contain the sugar residues of (1 → 2)-β-D-Glcp, (1 → 2)-α-D-Glcp, and (1 → 4)-α-D-Glcp. Using an HFD-fed mouse model with dyslipidemia, PCO could significantly suppress lipid metabolism disorders, characterized by the reduction of lipid accumulation and inflammatory responses in the blood and liver tissues. Based on the non-targeted metabolomic analysis and Spearman's correlation analysis, we presume that the preventive effect of PCO on dyslipidemia might contribute to the reversal of changed metabolic pathways, which were related to the metabolisms of glycerophospholipids, unsaturated fatty acids, amino acids, choline, bile acids, tryptophan, sphingolipids, and glutathione. Our research shed light on the potential application of PCO for the treatment of dyslipidemia.
With the increase in unhealthy lifestyles, obesity is increasingly common, which could cause many metabolic diseases. In recent research, natural product extracts have shown tremendous potential antiobesity effects via different mechanisms. In this review, we focused on widely adopted extraction methods, bioactive ingredients types, and antiobesity mechanisms of natural product extracts in the recent reports. The extraction methods include solid–liquid extraction, microwave‐assisted extractions, and supercritical fluid extraction. Moreover, the bioactive ingredients identified in natural product extracts are phenolic compounds, oligosaccharides, polysaccharides, and terpenoids. These exert antiobesity effects through multiple mechanisms, including suppressing the appetite, increasing energy expenditure, inhibiting enzyme activity, modulating lipid homeostasis and adipocyte lifecycle, reducing oxidative and inflammation, and improving intestinal bacteria. However, the antiobesity effects of natural products require further evaluation. Furthermore, the improvement of the bioavailability and effective and safe human dose of these bioactive ingredients should be the focus of future work.
Obesity is a major health crisis affecting over a third of the global population. This multifactorial disease is regulated via interoceptive neural circuits in the brain, whose alteration results in excessive body weight. Certain central neuronal populations in the brain are recognised as crucial nodes in energy homeostasis; in particular, the hypothalamic arcuate nucleus (ARC) region contains two peptide microcircuits that control energy balance with antagonistic functions: agouti-related peptide/neuropeptide-Y (AgRP/NPY) signals hunger and stimulates food intake; and pro-opiomelanocortin (POMC) signals satiety and reduces food intake. These neuronal peptides levels react to energy status and integrate signals from peripheral ghrelin, leptin, and insulin to regulate feeding and energy expenditure. To manage obesity comprehensively, it is crucial to understand cellular and molecular mechanisms of information processing in ARC neurons, since these regulate energy homeostasis. Importantly, a specific strategy focusing on ARC circuits needs to be devised to assist in treating obese patients and maintaining weight loss with minimal or no side effects. The aim of this review is to elucidate the recent developments in the study of AgRP-, NPY- and POMC-producing neurons, specific to their role in controlling metabolism. The impact of ghrelin, leptin, and insulin signalling via action of these neurons is also surveyed, since they also impact energy balance through this route. Lastly, we present key proteins, targeted genes, compounds, drugs, and therapies that actively work via these neurons and could potentially be used as therapeutic targets for treating obesity conditions.
Non-alcoholic steatohepatitis (NASH) is gradually becoming one of the most common and health-endangering diseases; therefore, it is very important to prevent the occurrence of NASH and prevent simple non-alcoholic fatty liver (NAFL) from further developing into NASH. We fed mice a high-fat diet (HFD, 60% fat) for 14 weeks to induce NAFL and then fed different doses of flaxseed powder (low (10%), middle (20%), and high (30%)) to the mice for 28 weeks. After the animal experiment, we analyzed fecal bile acid (BA) profiles of the HFD mice, flaxseed-fed (FLA-fed) mice, and control mice with a normal diet (10% fat) using a targeted metabolomics approach, and we analyzed the gut microbiota at the same time. We also investigated the mechanistic role of BAs in NASH and identified whether the altered BAs strongly bind to colonic FXR or TGR5. In the present study, we found that 28-week FLA treatment notably alleviated NASH development in NAFL model mice fed with an HFD, and the beneficial effects may be attributed to the regulation of and improvement in the gut flora- and microbiota-related BAs, which then activate the intestinal FXR-FGF15 and TGR5-NF-κB pathways. Our data indicate that FLA might be a promising functional food for preventing NASH through regulating microbiomes and BAs.
Previous work has shown that dietary flaxseed can significantly reduce cardiac damage from a coronary artery ligation-induced myocardial infarction. However, this model uses healthy animals and the ligation creates the infarct in an artificial manner. The purpose of this study was to determine if dietary flaxseed can protect the hearts of JCR:LA-cp rats, a model of genetic obesity and metabolic syndrome, from naturally occurring myocardial ischemic lesions. Male and female obese rats were randomized into four groups (n=8 each) to receive, for 12 weeks, either a) control diet (Con), b) control diet supplemented with 10% ground flaxseed (CFlax), c) a high-fat, high sucrose (HFHS) diet, or d) HFHS supplemented with 10% ground flaxseed (HFlax). Male and female JCR:LA-cp lean rats served as genetic controls and received similar dietary interventions. In male obese rats, serum total cholesterol and LDL-C were significantly lower in CFlax compared to Con. Obese rats on HFHS exhibited increased myocardial ischemic lesions and diastolic dysfunction regardless of sex. HFlax significantly lowered the frequency of cardiac lesions and improved diastolic function in male and female obese rats compared to HFHS. Blood pressures were similar in obese and lean rats. No aortic atherosclerotic lesions were detectable in any group. Collectively, this study shows that a HFHS diet increased myocardial ischemic lesion frequency and abolished the protective effect of female sex on cardiac function. More importantly, the data demonstrates dietary flaxseed protected against the development of small spontaneous cardiac infarcts despite the ingestion of a HFHS diet and the presence of morbid obesity.
1 | INTRODUÇÃO
A linhaça é a semente da planta do linho (Linum usitatissimum L.) pertencente à família Lineaceae (BEKHIT et al., 2018). Esta cultura apresenta-se em duas variedades nutricionalmente idênticas: a semente de coloração amarelo dourado e a marrom avermelhado (SONI et al., 2016). O uso da linhaça pelo ser humano remonta desde os tempos antigos (5000 a.C.) na mesopotâmia, por onde se espalhou ao redor do mundo, sendo hoje comercialmente explorada pelas indústrias de tecidos, papéis, tintas e alimentícia, esta última impulsionada por suas propriedades nutricionais e medicinais (SONI et al., 2016).
Nas últimas décadas, a linhaça despontou no cenário alimentício como um alimento com propriedades funcionais, ou seja, além das suas propriedades nutricionais básicas, a semente apresenta numerosos compostos biologicamente ativos e benéficos à saúde. A semente de linhaça, além de ser uma das fontes alimentícias com maior teor de ômega-3, tornando-a uma excelente alternativa para a incorporação dos ácidos graxos na dieta, também é fonte de fibras dietéticas, proteínas de alta qualidade, peptídeos bioativos, fitoesteróis e compostos fenólicos (WU et al., 2019; KANIKOWSKA et al., 2020).
O excelente perfil nutricional da semente de linhaça reflete nos seus efeitos benéficos à saúde humana. Estudos demonstram que a semente de linhaça pode ajudar na prevenção e tratamento de várias doenças, tais como: minimizar os distúrbios da obesidade, reduzir o risco de câncer de mama, controlar a diabetes, além de apresentar propriedades antiinflamatórias, antioxidantes e de regulação da função intestinal (CHISTHY & BISSU, 2016; WU et al., 2019).
Deste modo, a linhaça é de grande interesse para o mercado consumidor, sendo amplamente recomendada por nutricionistas, pesquisadores e médicos como um alimento funcional, seguro e barato para o tratamento de doenças (SHEKHARA et al., 2020).
O alimento pode ser incorporado nas dietas em suas diferentes formas, incluindo a semente inteira, ou os subprodutos da semente: farinha, goma, óleo, extrato/isolado fenólico, hidrolisado proteico, uma vez que há relatos de suas atividades anti-inflamatória, antioxidante e prebiótica (PARIKH et al., 2019).
Portanto, este capítulo busca fornecer uma revisão robusta e atualizada das atividades biológicas da semente de linhaça como recurso terapêutico à saúde humana.
There is a growing scientific view that the improvement of cancer by nonstarch polysaccharides (NSPs) is mediated by intestinal microbiota. Intestinal bacteria affect the supply of methyl donor substances and influence N⁶-methyladenosine (m⁶A) RNA methylation. As one of the epigenetic/epitranscriptomic modifications, m⁶A RNA methylation is closely related to the initiation and progression of cancers. This review summarizes the cancer-improving effects of NSPs through modulation of intestinal microbiota. It also summarizes the relationship between intestinal bacteria and the supply of methyl donor substances. Moreover, it also provides a summary of the effects of m⁶A RNA methylation on various types of cancer. The proposed mechanism is that, dietary consumed NSPs are utilized by specific intestinal bacteria and further reshape the microbial structure. Methyl donor substances will be directly or indirectly generated by the reshaped-microbiota, and affect the m⁶A RNA methylation of cancer-related and pro-carcinogenic inflammatory cytokine genes. Therefore, NSPs may change the m⁶A RNA methylation by affecting the methyl donor supply produced by intestinal microbiota and ameliorate cancer. This review discussed the possibility of cancer improvement of bioactive NSPs achieved by impacting RNA methylation via the intestinal microbiota, and it will offer new insights for the application of NSPs toward specific cancer prevention.
Background: Black fungi ( Auricularia auricula ) was known as one of the major mushrooms grown and cultivated all over the world, especially northeast Asia. It has
been proved that black fungi had tremendous biological functions, and thus was being
remarked to be a potential ingredient for the functional food.
Scope and approach: This review comprises a comprehensive research for the
isolation and characterization of bioactive components in black fungi and their potent
physiological activities. Meanwhile, chemical and metabolic methodologies are
introduced to clarify the specified mechanism and future challenges
Key findings and conclusions: Integrated research results showed that black fungi
contained some bioactive components such as polysaccharide, melanin and phenolic.
According to origin and isolation method, the structural features of polysaccharide and
melanin were significantly different. Health benefits such as antioxidant, hypoglycemic,
antitumor and immunostimulation could be exerted with black fungi components and
their derivatives. Besides, biological activity and physicochemical property of black
fungi enabled the application in the drug delivery and food production. Detailed
mechanisms confirmed that oxidative damage removal, immune signal transduction
and gut microbiota enhancement underlied the promising functionality of black fungi.
However, present research of black fungi still demands the more efficient extraction
and purification including subcritical water, ohmic, high hydrostatic pressure (HHP) and
two-phase partitioning. Challenges to some health benefits such as gut microbiotaimmune, dosage suitable for clinical practice and especially structure-function
relationship should also be worthwhile to increase the total functional value of black
fungi.
The pharmaceutical application of fungal polysaccharides has been extensively studied based on their multiple biological activities. However, the effect of Morchella esculenta polysaccharides on the development of atherosclerosis remains unknown. This study aims to investigate the anti-atherosclerotic effect of a novel polysaccharide (MCP) extracted from Morchella esculenta. The average molecular weight of MCP is 1.69 × 105 Da, and it is composed of glucose, mannose and galactose in the molar ratio of 1 : 1.9 : 0.51. LDLR-deficient (LDLR-/-) mice were fed high-fat diet (HFD) and administered intragastrically (i.g.) with saline or MCP dissolved in saline for 15 weeks. We found that MCP inhibited en face and sinus lesions. Moreover, serum levels of total and low-density lipoprotein cholesterol and triglyceride were decreased by MCP. The HFD-induced hepatic lipid accumulation was also attenuated by MCP. The underlying molecular mechanisms of anti-atherogenic and lipogenic effects of MCP might be attributed to reduced cholesterol synthesis by activating AMPKα signaling pathway and inhibiting SREBP2 expression. In addition, MCP-decreased serum triglyceride level is related to inhibiting LXRα expression. Taken together, these results indicate that MCP markedly alleviates atherosclerosis and M. esculenta can be used as a functional food additive to benefit patients with atherosclerosis.
Genome-wide DNA methylation was used to study the lipid-lowering effect of Cyclocarya paliurus (Batal) Iljinskaja polysaccharide (CPP). The objective of this study was to investigate the hypolipidemic effects and the potential underlying mechanisms of action of CPP-2 in high-fat emulsion (HFE)-induced mice. The results showed that CPP-2 reduced the level of genome-wide DNA methylation in the liver of HFE-induced mice, which had a lipid-lowering effect by regulating the AMP-activated protein kinase (AMPK) signaling-, fatty acid metabolism-, fatty acid biosynthesis- and adipocytokine signaling pathways. A series of lipid metabolism genes were screened out by conjoint analysis of the Gene Ontology (GO) terms and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways. Hereafter, fatty acid synthase (FAS) and peroxisome proliferators-activated receptor α (PPARα) as target genes were selected to validate the accuracy of the results. The findings demonstrated that CPP-2 might be effective in lowering the lipid content, thereby protecting against HFE-induced hyperlipidemia.
Probiotics and prebiotics for preventing and alleviating the degenerative changes associated with aging have received extensive attention. In the present work, Lactobacillus plantarum (L. plantarum) 69-2 with the highest antioxidant capacity combined with galacto-oligosaccharide (GOS) was used in aging model mice to evaluate the effect on aging and the regulation of gut microbiota. The combination of L. plantarum 69-2 and GOS supplementation could significantly (P < 0.05) improve liver function, antioxidant capacity, and inflammation accompanied by regulating the gut microbiota, increasing the short chain fatty acid (SCFA) levels, and activating the hepatic AMPK/SIRT1 regulatory pathway. The results showed that L. plantarum 69-2 and GOS could activate the hepatic AMPK/SIRT1 signaling pathway by regulating the gut microbiota and metabolites through the liver-gut axis to restore hepatic antioxidant activity to alleviate aging. The study provided a new insight for targeting the gut microbiota to relieve aging through the gut-liver axis.
The present study was conducted to investigate effects and mechanism of quercetin on lipids metabolism in broilers. 480 AA broilers were randomly allotted to four treatments (0, 0.2, 0.4, and 0.6 g/kg quercetin) for 42 days. Compared with the control, 0.6 g/kg quercetin significantly decreased percentage of abdominal fat ( P < 0.05); 0.2, 0.4, and 0.6 g/kg quercetin significantly decreased relative abundance of Lachnospiraceae and Desulfovibrionaceae ( P < 0.05, P < 0.05, P < 0.01; P < 0.01, P < 0.01, P < 0.01); 0.2 g/kg quercetin significantly increased mRNA expression of PI3K, AMPKα1, AMPKα2, AMPKβ2, LKB1 ( P < 0.01, P < 0.01, P < 0.05, P < 0.01, P < 0.05), and significantly reduced mRNA expression of SREBP1 and PPARγ ( P < 0.01, P < 0.05); 0.4 g/kg quercetin significantly increased mRNA expression of LKB1 and PKB ( P < 0.05, P < 0.01) and significantly reduced mRNA expression of ACC, HMGR, PPARγ, and SREBP1 ( P < 0.05, P < 0.01, P < 0.01, P < 0.01); 0.6 g/kg quercetin significantly increased mRNA expression of AMPKγ, LKB1, CPT1, PPARα, PKB ( P < 0.01, P < 0.01, P < 0.01, P < 0.05, P < 0.05), and significantly reduced the mRNA expression of PI3K, ACC, HMGR, PPARγ, SREBP1 ( P < 0.05, P < 0.05, P < 0.01, P < 0.01, P < 0.01); 0.2 g/kg quercetin significantly increased protein expression of AMPK ( P < 0.01); 0.6 g/kg quercetin significantly increased protein expression of LKB1 ( P < 0.01), 0.2 and 0.6 g/kg quercetin significantly increased protein expression of PI3K, PKB, CPT1 ( P < 0.05, P < 0.01, P < 0.05, P < 0.01, P < 0.01, P < 0.01), and significantly reduced protein expression of ACC and SREBP1 ( P < 0.01, P < 0.01, P < 0.01, P < 0.01). In conclusion, quercetin improved lipid metabolism by modulating gut microbial and AMPK/PPAR signaling pathway in broilers.
Rheumatoid arthritis (RA) causes swollen joints and irreversible joint damage and may even elevate cancer risks. Several bioactive nonstarch polysaccharides (NSPs) were reported to alleviate RA, but the key colonic genes accountable for this alleviation were elusive. Using collagen-induced arthritis as an RA model, colonic candidate genes related to RA were selected by transcriptome and methylome. The key genes were determined by comparing the transcriptome, methylome, and quantitative reverse transcription polymerase chain reaction profiles in RA rats with and without Lycium barbarum polysaccharides' treatment and further validated using Angelica sinensis polysaccharides and Astragalus propinquus polysaccharides for comparison. Both colonic genes γ-glutamyltransferase 7 (Ggt7) and angiotensin-I-converting enzyme (Ace) were downregulated by RA, and they were upregulated after L. barbarum polysaccharides' and A. sinensis polysaccharides' intervention that reduced the RA-caused hypermethylation status in nucleotide sites in the exon/promoter region of the two genes. However, the A. propinquus polysaccharides' intervention barely reduced the hypermethylation in the corresponding sites, failing to recover the expressions of these two genes and improve RA. Therefore, the colonic Ggt7 and Ace can be considered as key genes accountable for RA alleviation by bioactive NSP intervention. This study provides a more comprehensive insight into diet intervention to improve RA.
In this study, Pediococcus pentococcus PP04 isolated from the Northeast pickled cabbage had good gastrointestinal tolerance and can colonize in the intestine stably. C57BL/6N mice were fed a high-fat diet to build animal models and treated with Pediococcus pentosaceus PP04 to evaluate the antihyperlipidemia effect. After 8 weeks, the indicators of hyperlipidemia, liver injury, and inflammation were measured. The treatment of P. pentosaceus PP04 reduced the gain of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFAs), leptin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipopolysaccharides (LPS), and tumor necrosis factor-α (TNF-α) significantly. The western blotting results suggested P. pentosaceus PP04 ameliorated high-fat diet-induced hyperlipidemia by the AMPK signaling pathway, which stimulated lipolysis via upregulation of PPARα and inhibited lipogenesis by downregulation of SREBP-1c, fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD1) mainly. Furthermore, P. pentosaceus PP04 improved high-fat diet-induced oxidative stress effectively by triggering the Nrf2/CYP2E1 signaling pathway that enhanced the antioxidant activity including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).
Obesity and its related metabolic disorders have been a global pandemic. Recently, we found an anti-obesity effect of flaxseed polysaccharide (FP) that could be achieved by regulating intestinal microbiota. The anti-obesity effect of FP is mainly attributed to the metabolites produced by the interaction with FP, which remains to be elucidated. In this research, the in vitro effects of metabolites of FP fermented by fecal bacteria on energy metabolism and adipogenesis were investigated. The effect of energy metabolism was analyzed by mRNA and protein expression of the intestinal glucose transporters, including sodium dependent glucose transporter (SGLT1) and glucose transporter 2 (GLUT2), and glucose uptake in intestinal Caco-2 cells. The lipogenic effect were evaluated by Oil red O staining of intracellular lipid droplets and the mRNA and protein expression of peroxisome proliferator-activated receptor (PPAR) γ, CCAAT-enhancer-binding proteins (C/EBP) α and β in 3T3-L1 cells. The results showed the metabolites significantly inhibited glucose intake through downregulating the mRNA and protein expression of GLUT2 and SGLT1 in Caco-2 cells. Besides, they also led to the decrease of lipid accumulation through downregulating the mRNA and protein expression of PPARγ, C/EBPα, and C/EBPβ in differentiating adipocytes. The inhibitory effects on energy intake and adipogenesis were concentration dependent, and metabolites at physiological concentration showed the most significant effect. Metabolites of fecal bacteria fermenting FP inhibited energy intake and adipogenesis at physiological concentration, which might be one of the weight-loss mechanisms of FP-diet.
Objective
Metabolic syndrome is a complex medical condition that has become an alarming epidemic, but an effective therapy for this disease is still lacking. The use of the herbal formula Huangqisan (HQS) to treat diabetes is documented in the Chinese medical literature as early as 1117 A.D.; however, its therapeutic effects and underlying mechanisms remain elusive.
Methods
To investigate the beneficial effects of HQS on metabolic disorders, high-fat diet-induced obesity (DIO), leptin receptor dysfunction (db/db) and low-density lipoprotein receptor-knockout (LDLR−/−) mice were used. Obese mice were treated with either HQS or vehicle. Blood, liver tissue, white fat tissue and brown adipose tissue were harvested at the end of the treatment. Metabolic disease-related parameters were evaluated to test effects of HQS against diabetes, obesity and hyperlipidemia. Aortic arches from LDLR−/− mice were analyzed to investigate the effects of HQS on atherosclerosis. RNA-sequence, quantitative real-time polymerase chain reaction and Western blot were performed to investigate the mechanisms of HQS against metabolic disorder.
Results
HQS lowered body weight, fasting blood glucose and serum lipid levels and improved glucose tolerance and insulin sensitivity in DIO mice and db/db mice (P < 0.05). HQS also blocked atherosclerotic plaque formation in LDLR−/− mice. HQS suppressed de novo lipid synthesis by reducing the expression of messenger RNA for sterol regulatory element-binding factor 1, stearyl coenzyme A desaturase 1 and fatty acid synthase, and enhancing adenosine 5′-monophosphate-activated protein kinase signaling in both in vivo and in vitro experiments, indicating potential mechanisms for HQS’s activity against diabetes.
Conclusion
HQS is effective for reversing metabolic disorder and has the potential to be used as therapy for metabolic syndrome.
Diet greatly influences gut microbiota. Dietary methionine restriction (MR) prevents and ameliorates age-related or high-fat induced diseases, and prolongs life-span. This study aimed to reveal the impact of MR on gut microbiota in middle-aged mice with low-, medium-, high-fat diets. C57BL/6J mice were randomly divided into six groups with different MR and fat-content diets. Multiple indicators of intestinal function, fat accumulation, energy consumption, and inflammation were measured. 16S rRNA gene sequencing was used to analyze cecal microbiota. Our results indicated that MR considerably dropped the concentrations of lipopolysaccharides (LPS) and increased short-chain fatty acids (SCFAs) by upregulating the abundance of Corynebacterium and SCFAs-producing bacterium Bacteroides, Faecalibaculum, Roseburia, and downregulating the LPS-producing or pro-inflammatory bacterium Desulfovibrio and Escherichia-Shigella. These variations upon MR irrespective of fat content contributed to reducing fat accumulation, systemic inflammation, heat production, and strengthening the intestinal mucosal immunity barrier by LPS/LBP/CD14/TLR4 signal pathway in middle-aged mice.
Dyslipidemia and insulin resistance in obesity can lead to lipotoxicity and cellular damage. Renal lipotoxicity in association with an impairment of lipid metabolism induces renal damage through the activation of inflammation, ER stress, fibrosis and apoptosis. We investigated the effects of a combination treatment of the DPP-4 inhibitor vildagliptin and atorvastatin on renal lipotoxicity related to renal dysfunction and injury in a high-fat high-fructose diet (HFF)-induced insulin resistant condition. Male Wistar rats were fed on a high-fat diet and were given drinking water with 10% fructose for 16 weeks. After that, rats were divided into: no treatment (HFF), treatment with vildagliptin, atorvastatin and vildagliptin plus atorvastatin for 4 weeks. The results demonstrated that the combination treatment prominently improved insulin resistance, dyslipidemia and kidney morphological changes induced by HFF. These changes correlated well with the increased expression of nephrin and podocin and decreased urine protein. Notably, the combined treatment produced greater improvement in renal lipid metabolism through increasing fatty acid oxidation with the decreases in fatty acid transporters and fatty acid synthesis, thereby reducing renal lipid accumulation in HFF rats. The reduction in renal lipotoxicity via diminishing renal inflammation, ER stress, fibrosis and apoptosis was also more significant in the combined treatment group than in the other groups in which the drug was used as a monotherapy. In conclusion, the combination therapy produced synergistic beneficial effects on metabolic parameters, lipid metabolism and accumulation related to renal lipid accumulation-induced lipotoxicity and kidney injury in the HFF-induced insulin resistant model with improved outcomes.
The synergistic effects of Lactobacillus plantarum S58 (LP.S58) and hull-less barley β-glucan (β-G) on lipid accumulation in mice fed with a high-fat diet (HFD) were investigated. The body weight, serum lipid levels and lipid accumulation of adipose and liver tissues in the HFD-fed mice were inhibited after synergistic treatment with LP.S58 and β-G. In liver and adipose tissues, LP.S58 and β-G synergistically activated AMPK, reduced the expression of PPARγ, C/EBPα, SREBP-1c, FAS, SCD1 and LPL, and increased the expression of CPT-1 and HSL. The HFD-induced decreases in lipid metabolism-related hormones were reversed by LP.S58 and β-G. LP.S58 and β-G synergistically also increased the expression of colon tight junction proteins while suppressing systematic inflammation. LP.S58 and β-G ameliorated gut microbiological dysbiosis in HFD-fed mice. Correlations between serum parameters and gut microbiota were revealed. LP.S58 and β-G synergistically attenuated the HFD-induced lipid accumulation by activating AMPK signaling and regulating the gut microbiota.
Since the 1970s, the biological role of vanadium compounds has been discussed as insulin-mimetic or insulin-enhancer agents. The action of vanadium compounds has been investigated to determine how they influence the insulin signaling pathway. Khan and coworkers proposed key proteins for the insulin pathway study, introducing the concept “critical nodes”. In this review, we also considered critical kinases and phosphatases that participate in this pathway, which will permit a better comprehension of a critical node, where vanadium can act: a) insulin receptor, insulin receptor substrates, and protein tyrosine phosphatases; b) phosphatidylinositol 3′-kinase, 3-phosphoinositide-dependent protein kinase and mammalian target of rapamycin complex, protein kinase B, and phosphatase and tensin homolog; and c) insulin receptor substrates and mitogen-activated protein kinases, each node having specific negative modulators. Additionally, leptin signaling was considered because together with insulin, it modulates glucose and lipid homeostasis. Even in recent literature, the possibility of vanadium acting against metabolic diseases or cancer is confirmed although the mechanisms of action are not well understood because these critical nodes have not been systematically investigated. Through this review, we establish that vanadium compounds mainly act as phosphatase inhibitors and hypothesize on their capacity to affect kinases, which are critical to other hormones that also act on common parts of the insulin pathway.
The polysaccharide isolated from F. gummosa (FGP) was found homogenous with a weight average molecular weight (Mw) of 50.0 × 10³ g/mol and radius of gyration (Rg) of 105.3 nm. The FGP was an arabinogalactan with a backbone formed of →6)-β-Galp-1→ residues having random branching points at C-3 extended with either β-Galp-(1→3)-β-Galp-(1→ or α-Araf-(1→ side chain residues. FGP exhibited proliferative effect on RAW264.7 cells and induced macrophages to exert proinflammatory response releasing NO and up-regulating the transcription of cytokines including TNF-α, IL-1β, IL-6 and IL-12. The FGP induced NK-92 cells to up-regulate the expressions of TNF-α, IFN-γ, granzyme-B, perforin, NKG2D and FasL. The presence of p-NF- κB, p-ERK, p-JNK and p-p38 in RAW264.7 and NK-92 cells indicated their activation through NF-κB and MAPKs signaling pathways. These findings suggested that polysaccharides from F. gummosa are potent in boosting immune system and thus may be considered for further studies of biomedical applications.
High-fat high-fructose diet (HFF) in obesity can induce dyslipidemia and lipid accumulation both in kidney and liver which related to insulin resistance and lipotoxicity-induced cellular damage. We investigated whether dapagliflozin with or without atorvastatin could improve lipid accumulation-induced kidney and liver injury in HFF-induced insulin resistant rats. Male Wistar rats were fed with HFF for 16 weeks and then received drug treatments for 4 weeks; vehicle, dapagliflozin, atorvastatin and dapagliflozin plus atorvastatin treatment groups. HFF rats demonstrated insulin resistance, dyslipidemia, liver injury and renal dysfunction associated with impaired renal lipid metabolism and lipid accumulation. Dapagliflozin and combination treatment could improve HFF-induced insulin resistance, lipogenesis and lipotoxicity-related renal oxidative stress, inflammation, fibrosis and apoptosis leading to kidney dysfunction recovery. Liver injury-associated inflammation was also improved by these two regimens. Notably, the reduced lipid accumulation in liver and kidney that linked to an improvement of lipid oxidation was prominent in the combination treatment. Therefore, dapagliflozin combined with atorvastatin treatment exert the beneficial effects on lipid metabolism and lipotoxicity in liver and kidney injury via the attenuation of oxidative stress, fibrosis and apoptosis in insulin resistant model.
Flaxseed (Linum usitatissimum L.) is known as healthy food for its anti-obesity and lipid modulating properties. However, the effects of flaxseed polysaccharide (FSP) on metabolic syndrome (MetS) and gut microbiota are still poorly understood. Here, we investigated the effects of FSP on lipid metabolism and gut microbiota in high-fat-diet-fed mice. FSP effectively reduced the serum fasting glucose, total triglyceride and total cholesterol levels. FSP consumption adipose accumulation impacted the gut microbiome at different taxonomic levels by increasing the proportions of beneficial Akkermansia and Bifidobacterium and decreasing the disease or obesity associated Oscillospira and Odoribacteraceae. These changes were highly correlated with the regulation of expression levels of lipid metabolism involved genes in the liver. The restoration of total SCFAs, especially propionate and butyrate might be an important strategy for mitigating HFD induced metabolic disorders. These findings suggest that FSP may use as a prebiotic for preventing MetS by modulating the gut microbiota.
It is unclear if guar gum can alleviate colorectal cancer (CRC). We evaluated the effect of guar gum (unmodified) on the mortality, colon status, serous tumor necrosis factor-alpha (TNF-α) concentration, and gut microbial and colonic epithelial cell gene expression profiles in CRC mice and performed omics analyses to compare these with those of Ganoderma lucidum polysaccharide (GLP), whose main component is β-glucan (>90%). We found that guar gum had a CRC alleviating effect. However, it showed a 20% higher mortality rate, shorter colon length, worse colon status, larger number and size of tumors, higher concentration of serous TNF-α and upregulation of epithelial cell genes (Il10, Cytl1, Igkv7-33, Ighv1-14, Igfbp6 and Foxd3) compared to that of GLP. The higher relative abundance of Akkermansia, the alteration of microbial metabolic pathways, especially those involving chaperones and folding catalysts, fatty acid biosynthesis, glycerophospholipid metabolism, glycolysis/gluconeogenesis, lipid biosynthesis and pyruvate metabolism, and the upregulation of specific genes (Mcpt2, Mcpt9, Des and Sostdc1) were also determined in animals fed a guar gum diet. The results suggested that the alleviating effect of guar gum (an inexpensive polysaccharide) on CRC was inferior to that of GLP (a more expensive polysaccharide). This could potentially be attributed to the increased presence of Akkermansia, the alteration of 10 microbial metabolic pathways and the upregulation of 4 epithelial cell genes.
Lactobacillus plantarum LP104 was isolated with excellent antioxidant properties from kimchi. In order to evaluate the role of LP104 in improving hyperlipidemia in high-fat-diet mice, C57BL/6N mice were randomly assigned into three groups treated with different diets: normal chow (Control), HFD, and HFD with L. plantarum LP104. After eight weeks, L. plantarum LP104 treatment significantly reduced HFD-induced body weight gain and the levels of serum or liver TC, TG, LDL, ALT, AST, LPS and TNF-α, and elevated liver HDL levels. The liver lipid accumulation was decreased in L. plantarum LP104 group. L. plantarum LP104 could activate the AMPK/Nrf2/CYP2E1 related pathway and regulate expressions of related proteins by using western blotting. Therefore, L. plantarum LP104 will improve hyperlipidemia, liver metabolic disorders, and liver oxidative stress response.
As detailed above, the pharmacological activation of AMPK exerts positive effects on many aspects of cardiometabolic disease including hyperglycaemia, hyperlipidaemia, NAFLD, insulin resistance, hypertension and chronic low-grade inflammation. These effects are likely mediated through the simultaneous modulation of multiple molecular targets in several different tissues including adipose tissue, liver, immune cells such as macrophages, skeletal and cardiac muscle and the kidney (discussed below). In aggregate, these diverse disease-modifying activities might be expected to exert substantial positive effects on cardiometabolic risk in a more effective manner than existing standards of care such as metformin, GLP1 agonists and SGLT2 inhibitors. Clinical studies investigating these actions are currently underway with some AMPK-activating therapies.
The aim of this study was to assess inflammatory parameters, oxidative stress and energy metabolism in the hypothalamus of diet-induced obese mice. Male Swiss mice were divided into two study groups: control group and obese group. The animals in the control group were fed a diet with adequate amounts of macronutrients (normal-lipid diet), whereas the animals in the obese group were fed a high-fat diet to induce obesity. Obesity induction lasted 10 weeks, at the end of this period the disease model was validated in animals. The animals in the obese group had higher calorie consumption, higher body weight and higher weight of mesenteric fat compared to control group. Obesity showed an increase in levels of interleukin 1β and decreased levels of interleukin 10 in the hypothalamus. Furthermore, increased lipid peroxidation and protein carbonylation, and decreased level of glutathione in the hypothalamus of obese animals. However, there was no statistically significant difference in the activity of antioxidant enzymes, superoxide dismutase and catalase. The obese group had lower activity of complex I, II and IV of the mitochondrial respiratory chain, as well as lower activity of creatine kinase in the hypothalamus as compared to the control group. Thus, the results from this study showed changes in inflammatory markers, and dysregulation of metabolic enzymes in the pathophysiology of obesity.
Obesity promotes the development of numerous cancers, such as liver and colorectal cancers, which is at least partly due to obesity-induced, chronic, low-grade inflammation. In particular, the recruitment and activation of immune cell subsets in the white adipose tissue systemically increase proinflammatory cytokines, such as tumor necrosis factor α (TNFα) and interleukin-6 (IL-6). These proinflammatory cytokines not only impair insulin action in metabolic tissues, but also favor cancer development. Here, we review the current state of knowledge on how obesity affects inflammatory TNFα and IL-6 signaling in hepatocellular carcinoma and colorectal cancers.
Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease which affects ≈25% of the adult population worldwide, placing a tremendous burden on human health. The disease spectrum ranges from simple steatosis to steatohepatitis, fibrosis, and ultimately, cirrhosis and carcinoma, which are becoming leading reasons for liver transplantation. NAFLD is a complex multifactorial disease involving myriad genetic, metabolic, and environmental factors; it is closely associated with insulin resistance, metabolic syndrome, obesity, diabetes, and many other diseases. Over the past few decades, countless studies focusing on the investigation of noninvasive diagnosis, pathogenesis, and therapeutics have revealed different aspects of the mechanism and progression of NAFLD. However, effective pharmaceuticals are still in development. Here, the current epidemiology, diagnosis, animal models, pathogenesis, and treatment strategies for NAFLD are comprehensively reviewed, emphasizing the outstanding breakthroughs in the above fields and promising medications in and beyond phase II. Nonalcoholic fatty liver disease (NAFLD) is the most common liver disease which affects ≈25% of the adult population worldwide, placing a tremendous burden on human health. Here, the current understanding of NAFLD is reviewed, providing a critical summary of five areas including epidemiology, diagnosis, animal models, pathogenesis, and therapeutics, in hopes of bringing new insights into the characterization of NAFLD.
Obesity is a global disease that causes many metabolic disorders. However, effective agents for the prevention or treatment of obesity remain limited. This study investigated the anti-obesity effect and mechanism of chitosan oligosaccharide capsules (COSCs) on rats suffering from obesity induced by a high-fat diet (HFD). After the eight-week administration of COSCs on obese rats, the body weight gain, fat/body ratio, and related biochemical indices were measured. The hepatic expressions of the leptin signal pathway (JAK2-STAT3) and gene expressions of adipogenesis-related targets were also determined. Our data showed that COSCs can regulate body weight gain, lipids, serum alanine aminotransferase, and aspartate aminotransferase, as well as upregulate the hepatic leptin receptor-b (LepRb) and the phosphorylation of JAK2 and STAT3. Meanwhile, marked increased expressions of liver sterol regulatory element-binding protein-1c, fatty acid synthase, acetyl-CoA carboxylase, 3-hydroxy-3-methylglutaryl-CoA reductase, adiponectin, adipose peroxisome proliferator-activated receptor γ, CCAAT-enhancer binding protein α, adipose differentiation-related protein, and SREBP-1c were observed. The results suggested that COSCs activate the JAK2-STAT3 signaling pathway to alleviate leptin resistance and suppress adipogenesis to reduce lipid accumulation. Thus, they can potentially be used for obesity treatment.
General consumption of “western diet” characterized by high refined carbohydrates, fat and energy intake has resulted in a global obesity epidemics and related metabolic disturbance even for pregnant women. Pregnancy process is accompanied by substantial hormonal, metabolic and immunological changes during which gut microbiota is also remarkably remodeled. Dietary fiber has been demonstrated to have a striking role in shifting the microbial composition so as to improve host metabolism and health in non-pregnant individuals. The present study was conducted to investigate effects of adding a soluble dietary fiber inulin (0 or 1.5%) to low- or high- fat (0 or 5% fat addition) gestational diet on maternal and neonatal health and fecal microbial composition in a sow model. Results showed that inulin addition decreased the gestational body weight gain and fat accumulation induced by fat addition. Circulating concentrations of pro-inflammatory cytokine IL-6, adipokine leptin and chemerin were decreased by inulin supplementation. Inulin addition remarkably reduced the average BMI of newborn piglets and the within litter BMI distributions (%) ranging between 17 and 20 kg/m2, and increased the BMI distribution ranging between 14 and 17 kg/m2. 16S rRNA gene sequencing of the V3-V4 region showed that fecal microbial changes at different taxonomic levels triggered by inulin addition predisposed the pregnant sow to be thinner and lower inflammatory. Meanwhile, fecal microbial composition was also profoundly altered by gestation stage with distinct changes occurring at perinatal period. Most representative volatile fatty acid (VFA) producing-related genera changed dramatically when reaching the perinatal period and varied degrees of increases were detected with inulin addition. Fecal VFA concentrations failed to show any significant effect with dietary intervention, however, were markedly increased at perinatal period. Our findings indicate that positive microbial changes resulted by 1.5% soluble fiber inulin addition would possibly be the potential mechanisms under which maternal body weight, metabolic and inflammatory status and neonatal BMI were improved. Besides, distinct changes of microbial community at perinatal period indicated the mother sow is undergoing a catabolic state with increased energy loss and inflammation response at that period compared with other stages of gestation.
The brain–gut-axis is an interdependent system affecting neural functions and controlling our eating behaviour. In recent decades, neuroimaging techniques have facilitated its investigation. We systematically looked into functional and neurochemical brain imaging studies investigating how key molecules such as ghrelin, glucagon-like peptide-1 (GLP-1), peptide tyrosine-tyrosine (PYY), cholecystokinin (CCK), leptin, glucose and insulin influence the function of brain regions regulating appetite and satiety.
Study question:
How does a maternal diabetic hyperadiponectineamia affect signal transduction and lipid metabolism in rabbit preimplantation blastocysts?
Summary answer:
In a diabetic pregnancy increased levels of adiponectin led to a switch in embryonic metabolism towards a fatty acid-dependent energy metabolism, mainly affecting genes that are responsible for fatty acid uptake and turnover.
What is known already:
Although studies in cell culture experiments have shown that adiponectin is able to regulate lipid metabolism via 5'-AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor α (PPARα), data on the effects of adiponectin on embryonic lipid metabolism are not available. In a diabetic pregnancy in rabbits, maternal adiponectin levels are elevated fourfold and are accompanied by an increase in intracellular lipid droplets in blastocysts, implying consequences for the embryonic hormonal and metabolic environment.
Study design, size, duration:
Rabbit blastocysts were cultured in vitro with adiponectin (1 μg/ml) and with the specific AMPK-inhibitor Compound C for 15 min, 1 h and 4 h (N ≥ 3 independent experiments: for RNA analysis, n ≥ 4 blastocysts per treatment group; for protein analysis three blastocysts pooled per sample and three samples used per experiment). Adiponectin signalling was verified in blastocysts grown in vivo from diabetic rabbits with a hyperadiponectinaemia (N ≥ 3 independent experiments, n ≥ 4 samples per treatment group, eight blastocysts pooled per sample).
Participants/materials, setting, methods:
In these blastocysts, expression of molecules involved in adiponectin signalling [adaptor protein 1 (APPL1), AMPK, acetyl-CoA carboxylase (ACC), p38 mitogen-activated protein kinases (p38 MAPK)], lipid metabolism [PPARα, cluster of differentiation 36 (CD36), fatty acid transport protein 4 (FATP4), fatty acid binding protein (FABP4), carnitine palmityl transferase 1 (CPT1), hormone-senstive lipase (HSL), lipoprotein lipase (LPL)] and members of the insulin/insulin-like growth factor (IGF)-system [IGF1, IGF2, insulin receptor (InsR), IGF1 receptor (IGF1R)] were analyzed by quantitative RT-PCR and western blot. Analyses were performed in both models, i.e. adiponectin stimulated blastocysts (in vitro) and in blastocysts grown in vivo under increased adiponectin levels caused by a maternal diabetes mellitus.
Main results and the role of chance:
In both in vitro and in vivo models adiponectin increased AMPK and ACC phosphorylation, followed by an activation of the transcription factor PPARα, and CPT1, the key enzyme of β-oxidation (all P < 0.05 versus control). Moreover, mRNA levels of the fatty acid transporters CD36, FATP4 and FABP4, and HSL were upregulated by adiponectin/AMPK signalling (all P < 0.05 versus control). Under diabetic developmental conditions the amount of p38 MAPK was upregulated (P < 0.01 versus non-diabetic), which was not observed in blastocysts cultured in vitro with adiponectin, indicating that the elevated p38 MAPK was not related to adiponectin. However, a second effect of adiponectin has to be noted: its intensification of insulin sensitivity, by regulating IGF availability and InsR/IGF1R expression.
Large scale data:
Not applicable.
Limitations reasons for caution:
There are two main limitations for our study. First, human and rabbit embryogenesis can only be compared during blastocyst development. Therefore, the inferences from our findings are limited to the embryonic stages investigated here. Second, the increased adiponectin levels and lack of maternal insulin is only typical for a diabetes mellitus type one model.
Wider implications of the findings:
This is the first mechanistic study demonstrating a direct influence of adiponectin on lipid metabolism in preimplantation embryos. The numbers of young women with a diabetes mellitus type one are increasing steadily. We have shown that preimplantation embryos are able to adapt to changes in the uterine milieu, which is mediated by the adiponectin/AMPK signalling. A tightly hormonal control during pregnancy is essential for survival and proper development. In this control process, adiponectin plays a more important role than known so far.
Study funding/competing interest(s):
This work was supported by the German Research Council (DFG RTG ProMoAge 2155), the EU (FP7 Epihealth No. 278418, FP7-EpiHealthNet N°317146), COST Action EpiConcept FA 1201 and SALAAM BM 1308. The authors have no conflict(s) of interest to disclose.
AMP-activated protein kianse (AMPK) is a master sensor of cellular energy levels and a crucial regulator of nutrient metabolism such as the synthesis of fatty acids, glucose and protein as well as their oxidation to CO2 and water. Thus, AMPK signaling has important implications for fat deposition and glucose homeostasis in animals and humans. Much experimental and clinical evidence show that AMPK is a key therapeutic target for the prevention of diseases such as obesity, diabetes cancer, inflammation and cardiac dysfunction. In this review we highlight recent advances on the upstream and downstream targets of AMPK, as well as the specific mechanisms whereby AMPK regulates digestive functions and chronic energy balance in animals and humans.
Obesity, a major risk factor for the development of diabetes mellitus, cardiovascular diseases and certain types of cancer, arises from a chronic positive energy balance that is often due to unlimited access to food and an increasingly sedentary lifestyle on the background of a genetic and epigenetic vulnerability. Our understanding of the humoral and neuronal systems that mediate the control of energy homeostasis has improved dramatically in the past few decades. However, our ability to develop effective strategies to slow the current epidemic of obesity has been hampered, largely owing to the limited knowledge of the mechanisms underlying resistance to the action of metabolic hormones such as leptin and ghrelin. The development of resistance to leptin and ghrelin, hormones that are crucial for the neuroendocrine control of energy homeostasis, is a hallmark of obesity. Intensive research over the past several years has yielded tremendous progress in our understanding of the cellular pathways that disrupt the action of leptin and ghrelin. In this Review, we discuss the molecular mechanisms underpinning resistance to leptin and ghrelin and how they can be exploited as targets for pharmacological management of obesity.
Background
High-amylose maize resistant starch type 2 (HAM-RS2) stimulates gut-derived satiety peptides and reduces adiposity in animals. Human studies have not supported these findings despite improvements in glucose homeostasis and insulin sensitivity after HAM-RS2 intake which can lower adiposity-related disease risk. The primary objective of this study was to evaluate the impact of HAM-RS2 consumption on blood glucose homeostasis in overweight, healthy adults. We also examined changes in biomarkers of satiety (glucagon-like peptide-1 [GLP-1], peptide YY [PYY], and leptin) and body composition determined by anthropometrics and dual-energy x-ray absorptiometry, dietary intake, and subjective satiety measured by a visual analogue scale following HAM-RS2 consumption. Methods
Using a randomized-controlled, parallel-arm, double-blind design, 18 overweight, healthy adults consumed either muffins enriched with 30 g HAM-RS2 (n = 11) or 0 g HAM-RS2 (control; n = 7) daily for 6 weeks. The HAM-RS2 and control muffins were similar in total calories and available carbohydrate. ResultsAt baseline, total PYY concentrations were significantly higher 120 min following the consumption of study muffins in the HAM-RS2 group than control group (P = 0.043). Within the HAM-RS2 group, the area under the curve (AUC) glucose (P = 0.028), AUC leptin (P = 0.022), and postprandial 120-min leptin (P = 0.028) decreased independent of changes in body composition or overall energy intake at the end of 6 weeks. Fasting total PYY increased (P = 0.033) in the HAM-RS2 group, but changes in insulin or total GLP-1 were not observed. Mean overall change in subjective satiety score did not correlate with mean AUC biomarker changes suggesting the satiety peptides did not elicit a satiation response or change in overall total caloric intake. The metabolic response from HAM-RS2 occurred despite the habitual intake of a moderate-to-high-fat diet (mean range 34.5% to 39.4% of total calories). Conclusion
Consuming 30 g HAM-RS2 daily for 6 weeks can improve glucose homeostasis, lower leptin concentrations, and increase fasting PYY in healthy overweight adults without impacting body composition and may aid in the prevention of chronic disease. However, between-group differences in biomarkers were not observed and future research is warranted before specific recommendations can be made. Trial registrationNone.
Objective:
To investigate whether or not berberine could improve metabolic status of high-fat-fed rats through modulation of microbiota-gut-brain axis.
Methods:
Berberine was administered on high-fat-fed Sprague-Dawley rats. Brain-gut hormones were detected, and changes of gut microbiota were analyzed by 16S rRNA gene sequencing.
Results:
Berberine could reduce weight gain and lipolysis in the high-fat diet-fed group. Moreover, trends of ameliorated insulin resistance and decreased endogenous glucose production were observed. In addition, the microbiota-gut-brain axis was found to be modulated, including structural and diversity changes of microbiota, elevated serum glucagon-like peptide-1 and neuropeptide Y level, decreased orexin A level, up-regulated glucagon-like peptide-1 receptor mRNA level as well as ultra-structural improvement of the hypothalamus.
Conclusion:
Taken together, our findings suggest that berberine improved metabolic disorders induced by high-fat diet through modulation of the microbiota-gut-brain axis.
To quantify the role of BMI and metabolic dysfunction in the risk of development of type 2 diabetes in patients at high risk or with manifest vascular disease.
A total of 6,997 patients participating in the prospective Secondary Manifestations of ARTerial disease (SMART) cohort study were classified according to BMI and metabolic dysfunction, defined as three or more of the modified NCEP metabolic syndrome criteria (waist circumference replaced by hs-CRP ≥2 mg/L). Risk of type 2 diabetes (assessed with biannually questionnaires) was estimated with Cox proportional hazard analysis.
During a median follow-up of 6.0 years (interquartile range 3.1-9.1 years), 519 patients developed type 2 diabetes (incidence rate 12/1,000 person-years). In the absence of metabolic dysfunction (≤2 NCEP criteria) adiposity increased the risk of type 2 diabetes compared with normal weight patients (HR 2.5 [95% CI 1.5-4.2] for overweight and HR 4.3 [95% CI 2.2-8.6] for obese patients). In the presence of metabolic dysfunction (≥3 NCEP criteria) an increased risk of type 2 diabetes was observed in patients with normal weight (HR 4.7 [95% CI 2.8-7.8]), overweight (HR 8.5 [95% CI 5.5-13.4]), and obesity (HR 16.3 [95% CI 10.4-25.6]) compared with normal weight patients without metabolic dysfunction.
Adiposity, even in the absence of metabolic dysfunction, is a risk factor for type 2 diabetes. Moreover, presence of metabolic dysfunction increases the risk of type 2 diabetes in all BMI categories. This supports assessment of adiposity and metabolic dysfunction in patients with vascular disease or at high risk for cardiovascular events.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
There is controversy over previous findings that a high ratio of Firmicutes to Bacteriodetes helps obese animals harvest energy from the diet. To further investigate the relationship between microbial composition and energy harvest, microbial adaptation to diet and time should be considered. In this study, lean and obese rats were successfully induced with low-fat and high-fat diets. An 8-week high soyabean fibre (HSF)-containing diet was then fed to investigate the interaction between the diet and the rats’ gut microbiota, as well as their influence on rats’ growth. Rats’ body weight (BW) was recorded weekly; their plasma lipids and their gut microbiota at week 11, 15 and 19 were analysed. After the consumption of the HSF diet, BW of lean rats increased significantly (
P
<0·05), but no significant alteration in BW was found in obese rats. The average content of plasma cholesterol was lowered and that of TAG was upgraded in both the groups when fed the HSF diet. There was no significant difference observed at each period between lean and obese rats. In the group of lean rats, the diversity of gut microbiota was elevated strongly (
P
<0·01), and bacteria from phylum Firmicutes and Bacteroidetes were both increased largely (
P
<0·01); however, the bacterial diversity and composition in obese rats were less altered after the HSF diet control. In conclusion, the increased Firmicutes and Bacteriodetes might relate to lean rats’ higher BW gain; ‘obese microbiota’ could not help the hosts harvest more energy from the HSF diet.
The dietary fiber guar gum has beneficial effects on obesity, hyperglycemia and hypercholesterolemia in both humans and rodents. The major products of colonic fermentation of dietary fiber, the short-chain fatty acids (SCFAs), have been suggested to play an important role. Recently, we showed that SCFAs protect against the metabolic syndrome via a signaling cascade that involves peroxisome proliferator-activated receptor (PPAR) γ repression and AMP-activated protein kinase (AMPK) activation. In this study we investigated the molecular mechanism via which the dietary fiber guar gum protects against the metabolic syndrome. C57Bl/6J mice were fed a high-fat diet supplemented with 0% or 10% of the fiber guar gum for 12 weeks and effects on lipid and glucose metabolism were studied. We demonstrate that, like SCFAs, also guar gum protects against high-fat diet-induced metabolic abnormalities by PPARγ repression, subsequently increasing mitochondrial uncoupling protein 2 expression and AMP/ATP ratio, leading to the activation of AMPK and culminating in enhanced oxidative metabolism in both liver and adipose tissue. Moreover, guar gum markedly increased peripheral glucose clearance, possibly mediated by the SCFA-induced colonic hormone glucagon-like peptide-1. Overall, this study provides novel molecular insights into the beneficial effects of guar gum on the metabolic syndrome and strengthens the potential role of guar gum as a dietary-fiber intervention.
Short-chain fatty acids (SCFAs) are the main products of dietary fiber fermentation and are believed to drive the fiber-related prevention of the metabolic syndrome. Here we show that dietary SCFAs induce a peroxisome proliferator-activated receptor (PPAR) γ-dependent switch from lipid synthesis to utilization. Dietary SCFA supplementation prevented and reversed high-fat diet-induced metabolic abnormalities in mice by decreasing PPARγ expression and activity. This increased the expression of mitochondrial uncoupling protein 2 and raised the AMP/ATP ratio, thereby stimulating oxidative metabolism in liver and adipose tissue via AMP-activated protein kinase. The SCFA-induced reduction in body weight and stimulation of insulin sensitivity were absent in mice with adipose-specific disruption of PPARγ. Similarly, SCFA-induced reduction of hepatic steatosis was absent in mice lacking hepatic PPARγ. These results demonstrate that adipose and hepatic PPARγ are critical mediators of the beneficial effects of SCFA on the metabolic syndrome, with clearly distinct and complementary roles. Our findings indicate that SCFAs may be used therapeutically as cheap and selective PPARγ modulators.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
Sirtuin 1 (SIRT1), an NAD(+)-dependent protein deacetylase, regulates a host of target proteins, including peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α (PGC-1α), a transcriptional coregulator that binds to numerous transcription factors in response to deacetylation to promote mitochondrial biogenesis and oxidative metabolism. Our laboratory and others have shown that adipose triglyceride lipase (ATGL) increases the activity of the nuclear receptor PPAR-α, a PGC-1α binding partner, to promote fatty acid oxidation. Fatty acids bind and activate PPAR-α; therefore, it has been presumed that fatty acids derived from ATGL-catalyzed lipolysis act as PPAR-α ligands. We provide an alternate mechanism that links ATGL to PPAR-α signaling. We show that SIRT1 deacetylase activity is positively regulated by ATGL to promote PGC-1α signaling. In addition, ATGL mediates the effects of β-adrenergic signaling on SIRT1 activity, and PGC-1α and PPAR-α target gene expression independent of changes in NAD(+). Moreover, SIRT1 is required for the induction of PGC-1α/PPAR-α target genes and oxidative metabolism in response to increased ATGL-mediated lipolysis. Taken together, this work identifies SIRT1 as a critical node that links β-adrenergic signaling and lipolysis to changes in the transcriptional regulation of oxidative metabolism.
© 2015 by the American Diabetes Association. Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered.
To compare the effects of dietary fibers on hepatic cellular signaling in mice.
Mice were randomly divided into four groups (n = 9/group): high-fat diet (HFD) control, cellulose, psyllium, and sugarcane fiber (SCF) groups. All mice were fed a HFD with or without 10% dietary fiber (w/w) for 12 weeks. Body weight, food intake, fasting glucose, and fasting insulin levels were measured. At the end of the study, hepatic fibroblast growth factor (FGF) 21, AMP-activated protein kinase (AMPK) and insulin signaling protein content were determined.
Hepatic FGF21 content was significantly lowered, but βKlotho, fibroblast growth factor receptor 1, fibroblast growth factor receptor 3, and peroxisome proliferator-activated receptor alpha proteins were significantly increased in the SCF group compared with those in the HFD group (P < 0.01). SCF supplementation also significantly enhanced insulin and AMPK signaling, as well as decreased hepatic triglyceride and cholesterol in comparison with the HFD mice. The study has shown that dietary fiber, especially SCF, significantly attenuates lipid accumulation in the liver by enhancing hepatic FGF21, insulin, and AMPK signaling in mice fed a HFD.
This study suggests that the modulation of gastrointestinal factors by dietary fibers may play a key role in both enhancing hepatic multiple cellular signaling and reducing lipid accumulation.
Dietary fiber and whole grains contain a unique blend of bioactive components including resistant starches, vitamins, minerals, phytochemicals and antioxidants. As a result, research regarding their potential health benefits has received considerable attention in the last several decades. Epidemiological and clinical studies demonstrate that intake of dietary fiber and whole grain is inversely related to obesity, type two diabetes, cancer and cardiovascular disease (CVD). Defining dietary fiber is a divergent process and is dependent on both nutrition and analytical concepts. The most common and accepted definition is based on nutritional physiology. Generally speaking, dietary fiber is the edible parts of plants, or similar carbohydrates, that are resistant to digestion and absorption in the small intestine. Dietary fiber can be separated into many different fractions. Recent research has begun to isolate these components and determine if increasing their levels in a diet is beneficial to human health. These fractions include arabinoxylan, inulin, pectin, bran, cellulose, β-glucan and resistant starch. The study of these components may give us a better understanding of how and why dietary fiber may decrease the risk for certain diseases. The mechanisms behind the reported effects of dietary fiber on metabolic health are not well established. It is speculated to be a result of changes in intestinal viscosity, nutrient absorption, rate of passage, production of short chain fatty acids and production of gut hormones. Given the inconsistencies reported between studies this review will examine the most up to date data concerning dietary fiber and its effects on metabolic health.
AMPK has emerged as a critical mechanism for salutary effects of polyphenols on lipid metabolic disorders in type 1 and type 2 diabetes. Here we demonstrate that AMPK interacts with and directly phosphorylates sterol regulatory element binding proteins (SREBP-1c and -2). Ser372 phosphorylation of SREBP-1c by AMPK is necessary for inhibition of proteolytic processing and transcriptional activity of SREBP-1c in response to polyphenols and metformin. AMPK stimulates Ser372 phosphorylation, suppresses SREBP-1c cleavage and nuclear translocation, and represses SREBP-1c target gene expression in hepatocytes exposed to high glucose, leading to reduced lipogenesis and lipid accumulation. Hepatic activation of AMPK by the synthetic polyphenol S17834 protects against hepatic steatosis, hyperlipidemia, and accelerated atherosclerosis in diet-induced insulin-resistant LDL receptor-deficient mice in part through phosphorylation of SREBP-1c Ser372 and suppression of SREBP-1c- and -2-dependent lipogenesis. AMPK-dependent phosphorylation of SREBP may offer therapeutic strategies to combat insulin resistance, dyslipidemia, and atherosclerosis.
The leptin receptor is a class I transmembrane protein with either a short or a long cytoplasmic domain. Using chemical cross-linking we have analyzed the binding of leptin to its receptor. Cross-linking of radiolabeled leptin to different isoforms of the leptin receptor expressed on COS-1 cells reveals leptin receptor monomer, homodimer, and oligomer complexes. Cotransfection of the long and short form of the leptin receptor did not provide any evidence for the formation of heterodimer complexes. Soluble forms consisting of either the entire extracellular domain or the two cytokine receptor homologous domains of the leptin receptor were purified to homogeneity from recombinant baculovirus-infected insect cells by leptin affinity chromatography. Gel filtration chromatography showed that these proteins exist in a dimeric form. Analysis of the complex formed between soluble leptin receptor and leptin by native polyacrylamide gel electrophoresis, and data obtained from the amino acid composition of the complex provide direct evidence that the extracellular domain of the leptin receptor binds leptin in a 1:1 ratio.
Binding of leptin to the leptin receptor is crucial for body weight and bone mass regulation in mammals. Leptin receptors were shown to exist as dimers, but the role of dimerization in receptor activation remains unknown. Using a quantitative Bioluminescence Resonance Energy Transfer approach, we show here in living cells that approximately 60% of the leptin receptor exists as constitutive dimers at physiological expression levels in the absence of leptin. No further increase in leptin receptor dimerization was detected in the presence of leptin. Importantly, in cells expressing the short leptin receptor isoform, leptin promoted a robust enhancement of energy transfer signals that reflect specific conformational changes of pre-existing leptin receptor dimers and that may be used as read-out in screening assays for leptin receptor ligands. Both leptin receptor dimerization and the leptin-induced energy transfer were Janus kinase 2-independent. Taken together, our data support a receptor activation model based on ligand-induced conformational changes rather than ligand-induced dimerization.
Despite its importance in terms of energy homeostasis, the role of AMP-activated protein kinase in adipose tissue remains controversial. Initial studies have described an anti-lipolytic role for AMP-activated protein kinase, whereas more recent studies have suggested the converse. Thus we have addressed the role of AMP-activated protein kinase in adipose tissue by modulating AMP-activated protein kinase activity in primary rodent adipocytes using pharmacological activators or by adenoviral expression of dominant negative or constitutively active forms of the kinase. We then studied the effects of AMP-activated protein kinase activity modulation on lipolytic mechanisms. Finally, we analyzed the consequences of a genetic deletion of AMP-activated protein kinase in mouse adipocytes. AMP-activated protein kinase activity in adipocytes is represented mainly by the alpha(1) isoform and is induced by all of the stimuli that increase cAMP in adipocytes, including fasting. When AMP-activated protein kinase activity is increased by 5-aminoimidazole-4-carboxamide-riboside, phenformin, or by the expression of a constitutively active form, isoproterenol-induced lipolysis is strongly reduced. Conversely, when AMP-activated protein kinase activity is decreased either by a dominant negative form or in AMP-activated protein kinase alpha(1) knock-out mice, lipolysis is increased. We present data suggesting that AMP-activated protein kinase acts on hormone-sensitive lipase by blocking its translocation to the lipid droplet. We conclude that, in mature adipocytes, AMP-activated protein kinase activation has a clear anti-lipolytic effect.
Overconsumption and increased selection of high fat (HF) foods contribute to the development of common obesity. Because the hypothalamic melanocortin (MC) system plays an integral role in the regulation of food intake and dietary choice, we tested the hypothesis that proneness (-P) or resistance (-R) to dietary-induced obesity (DIO) may be due to differences in MC function. We found that prior to developing obesity and while still maintained on chow, acute, central administration of MTII, an MC agonist, produced a greater anorectic response in DIO-P rats than in DIO-R rats. However, after only 5 days of exclusive HF feeding, the DIO-R rats had significantly greater suppression of intake after MTII treatment than they did when maintained on chow. In addition, the DIO-P rats were much less responsive to MTII treatment than the DIO-R rats after only 5 days of the HF diet. In fact, MTII-induced anorexia during HF feeding correlated negatively with body weight gained on the HF diet. These results suggest that the voluntary decrease of HF feeding in DIO-R rats may be mediated by increased endogenous MC signaling, a signal likely compromised in DIO-P rats. Differences in MC regulation may also explain the observed preference for HF over a lower fat food choice in DIO-P rats. Finally, the results indicate that responses to exogenous MC challenge can be used to predict proneness or resistance to DIO.
The World Health Organization defines overweight and obesity as the condition where excess or abnormal fat accumulation increases risks to health. The prevalence of obesity is increasing worldwide and is around 20% in ICU patients. Adipose tissue is highly metabolically active, and especially visceral adipose tissue has a deleterious adipocyte secretory profile resulting in insulin resistance and a chronic low-grade inflammatory and procoagulant state. Obesity is strongly linked with chronic diseases such as type 2 diabetes, hypertension, cardiovascular diseases, dyslipidemia, non-alcoholic fatty liver disease, chronic kidney disease, obstructive sleep apnea and hypoventilation syndrome, mood disorders and physical disabilities. In hospitalized and ICU patients and in patients with chronic illnesses, a J-shaped relationship between BMI and mortality has been demonstrated, with overweight and moderate obesity being protective compared with a normal BMI or more severe obesity (the still debated and incompletely understood “obesity paradox”). Despite this protective effect regarding mortality, in the setting of critical illness morbidity is adversely affected with increased risk of respiratory and cardiovascular complications, requiring adapted management. Obesity is associated with increased risk of AKI and infection, may require adapted drug dosing and nutrition and is associated with diagnostic and logistic challenges. In addition, negative attitudes toward obese patients (the social stigma of obesity) affect both health care workers and patients.
Maximizing the benefits of investments in obesity research requires effective interventions to be adopted and disseminated broadly across populations (scaled‐up). However, interventions often need considerable adaptation to enable implementation at scale, a process that can reduce the effects of interventions. A systematic review was undertaken for trials that sought to deliver an obesity intervention to populations on a larger scale than a preceding randomized controlled trial (RCT) that established its efficacy. Ten scaled‐up obesity interventions (six prevention and four treatment) were included. All trials made adaptations to interventions as part of the scale‐up process, with mode of delivery adaptations being most common. A meta‐analysis of body mass index (BMI)/BMI z score (zBMI) from three prevention RCTs found no significant benefit of scaled‐up interventions relative to control (standardized mean difference [SMD] = 0.03; 95% CI, −0.09 to 0.15, P = 0.639 − I2 = 0.0%). All four treatment interventions reported significant improvement on all measures of weight status. Pooled BMI/zBMI data from prevention trials found significantly lower effects among scaled‐up intervention trials than those reported in pre–scale‐up efficacy trials (SMD = −0.11; 95% CI, −0.20 to −0.02, P = 0.018 − I2 = 0.0%). Across measures of weight status, physical activity/sedentary behaviour, and nutrition, the effects reported in scaled‐up interventions were typically 75% or less of the effects reported in pre–scale‐up efficacy trials. The findings underscore the challenge of scaling‐up obesity interventions.
Background
One anastomosis gastric bypass (OAGB) is increasingly used in the treatment of morbid obesity. However, the efficacy and safety outcomes of this procedure remain debated. We report the results of a randomised trial (YOMEGA) comparing the outcomes of OAGB versus standard Roux-en-Y gastric bypass (RYGB).
Methods
This prospective, multicentre, randomised non-inferiority trial, was held in nine obesity centres in France. Patients were eligible for inclusion if their body-mass index (BMI) was 40 kg/m² or higher, or 35 kg/m² or higher with the presence of at least one comorbidity (type 2 diabetes, high blood pressure, obstructive sleep apnoea, dyslipidaemia, or arthritis), and were aged 18–65 years. Key exclusion criteria were a history of oesophagitis, Barrett's oesophagus, severe gastro-oesophageal reflux disease resistant to proton-pump inhibitors, and previous bariatric surgery. Participants were randomly assigned (1:1) to OAGB or RYGB, stratified by centre with blocks of variable size; the study was open-label, with no masking required. RYGB consisted of a 150 cm alimentary limb and a 50 cm biliary limb and OAGB of a single gastrojejunal anastomosis with a 200 cm biliopancreatic limb. The primary endpoint was percentage excess BMI loss at 2 years. The primary endpoint was assessed in the per-protocol population and safety was assessed in all randomised participants. This study is registered with ClinicalTrials.gov, number NCT02139813, and is now completed.
Findings
From May 13, 2014, to March 2, 2016, of 261 patients screened for eligibility, 253 (97%) were randomly assigned to OAGB (n=129) or RYGB (n=124). Five patients did not undergo their assigned surgery, and after undergoing their surgery 14 were excluded from the per-protocol analysis (seven due to pregnancy, two deaths, one withdrawal, and four revisions from OAGB to RYGB) In the per-protocol population (n=117 OAGB, n=117 RYGB), mean age was 43·5 years (SD 10·8), mean BMI was 43·9 kg/m² (SD 5·6), 176 (75%) of 234 participants were female, and 58 (27%) of 211 with available data had type 2 diabetes. After 2 years, mean percentage excess BMI loss was −87·9% (SD 23·6) in the OAGB group and −85·8% (SD 23·1) in the RYGB group, confirming non-inferiority of OAGB (mean difference −3·3%, 95% CI −9·1 to 2·6). 66 serious adverse events associated with surgery were reported (24 in the RYGB group vs 42 in the OAGB group; p=0·042), of which nine (21·4%) in the OAGB group were nutritional complications versus none in the RYGB group (p=0·0034).
Interpretation
OAGB is not inferior to RYGB regarding weight loss and metabolic improvement at 2 years. Higher incidences of diarrhoea, steatorrhoea, and nutritional adverse events were observed with a 200 cm biliopancreatic limb OAGB, suggesting a malabsorptive effect.
Funding
French Ministry of Health.
Konjac glucomannan (KGM) is a dietary fiber hydrocolloidal polysaccharide isolated from the tubers of Amorphophallus konjac. Over the last few decades, the purified KGM has been offered as a food additive as well as a dietary supplement in many countries. Also, a diet containing konjac flour or KGM is considered as healthier, and these foods are popular in many Asian and European markets. Further, due to the adhesive property of KGM, it can form a defensive covering on the surface of the intestine. Additionally, KGM can reduce the levels of glucose, cholesterol, triglycerides, and blood pressure and can enable weight loss. Its wide-ranging effects prevent many chronic diseases through the regulation of metabolism. In this review, the recent studies on the health benefits such as anti-diabetic, anti-obesity, laxative, prebiotic, and anti-inflammatory activities of KGM were discussed. Also, this review deals with the applications of KGM and its derivatives in bio-technical, pharmaceutical, tissue engineering, fine chemical fields, etc.
The function of flaxseed gum (FG) on blood glucose control makes it possible for body weight loss. This experiment was to investigate the anti-obesity effect of FG and the alteration of gut microbiota. Diets with high, middle and low doses of FG were applied to feed obese rats for 5 weeks. The body weights, serum biochemical indices, body fats, short-chain fatty acid (SCFA) contents and metagenomic information of gut microbiota were analyzed. The results showed the FG diet reduced body weights, body fats and total triacylglycerols, and reshaped rat’s cecal microbial compositions. The anti-obesity effect of FG could be achieved by appetite suppression by reducing the relative abundance of Firmicutes and/or the Firmicutes/Bacteroidetes ratio and regulating some specific bacteria. The genus Clostridium might be the key one for the degradation of FG and production of SCFAs. SCFAs may not be involved in this weight-loss effect.
Obesity is a risk factor for many chronic diseases, and the anti-obesity effect of starch in a whole grain-like structural form (WGLSF) prepared through co-gelation with oat -glucan and alginate was studied using high-fat (HF) induced obese Male C57BL/6J mice. In vitro human fecal fermentation of WGLSF-starch showed a slower rate of fermentation and a higher production of butyric acid (132.0 mol/50 mg sample) when compared to the physical mixture counterpart of starch, -glucan, and alginate (PM) (110.5mol/50 mg) or -glucan itself (96.2mol/50 mg). The body weight gain of obese mice fed on HF-WGLSF diet was significantly reduced (42.0% lower than HF group, 30.2% lower than the physical mixture) with decreased cell size in white adipose tissue and similar levels of serum lipid profiles to the control of low-fat (LF) group. Western blotting experiments showed down-regulated lipogenic transcription factor of SREBP-1c and fatty acid synthase (FAS), but the lipid-oxidation related transcription factor of peroxisome proliferator-activated receptor-α (PPAR-α) and phosphorylated AMP-activated protein kinase (p-AMPK) were up-regulated. Energy metabolism analysis revealed increased lipid-sourced energy expenditure with higher heat production and respiratory exchange ratio. Consistently, the expression of hypothalamic pro-opiomelanocortin (POMC), favoring energy expenditure, was increased significantly while the neuropeptide Y (NPY) was reduced. Thus, the increased energy expenditure stimulated by starch in a whole-grain-like structural form is responsible for the reduced the body weight gain of obese mice fed on high fat-based diet.
Tissue damage and inflammation are important triggers for regeneration and fibrosis. Tissue damage not only induces inflammation in general, it also determines the type and polarization of inflammation by recruiting and activating a variety of different cells types of the innate and adaptive immune system. This review focuses on the pathways leading from tissue damage to inflammation, from inflammation to fibrosis and from fibrosis to function. It covers the pro- and antifibrotic properties of immunological mediators released from T cells, monocytes/macrophages, innate lymphoid cells, basophils and eosinophils and takes into account that extracellular matrix proteins are not only produced by mesenchymal fibroblasts but also by infiltrating hematopoietic cells. The special requirements for activation and recruitment of these so called fibrocytes are also summarized.
Purpose of review:
Adipogenesis has been extensively studied in the context of carbohydrate and lipid metabolism. However, little information exists on the role of amino acid metabolism during adipocyte differentiation. Here, we review how branched-chain amino acid (BCAA) metabolism is modified during adipogenesis and, due to the limited information in the area, address questions that remain to be answered with further research.
Recent findings:
BCAAs are rapidly consumed during adipocyte differentiation and are indispensable for this process. Furthermore, we describe how BCAA catabolic enzymes and the metabolic fate of BCAAs are modified during adipogenesis.
Summary:
Obesity is a chronic disease characterized by increased adipose tissue due to either an increase in the size (hypertrophy) and/or number of adipocytes (hyperplasia). Hyperplasia is determined by the rate of adipogenesis. Therefore, understanding the mechanism that modulates adipogenesis in the context of amino acid metabolism will help to establish pharmacological and dietary interventions involving the type and amount of dietary protein for the treatment of obesity and its associated comorbidities.Video abstract http://links.lww.com/COCN/A11.
Scope:
Evidence from animal experiments and clinical medicine suggest that high dietary fiber intake, followed by gut microbiota-mediated fermentation, decreases trimethylamine (TMA) metabolism, the mechanism of which, however, remains unclear. The objective of this analysis was to evaluate, using mice fed with red meat, the effects of soluble dietary fiber (SDF) intervention on TMA metabolism.
Methods and results:
Low- or high-dose soluble dietary fiber (SDF) from natural wheat bran (LN and HN, low- and high-dose natural SDF), fermented wheat bran (LF and HF, low- and high-dose fermented SDF), and steam-exploded wheat bran (LE and HE, low- and high-dose exploded SDF groups) were used to examine whether SDF interventions in mice fed with red meat can alter TMA and trimethylamine N-oxide (TMAO) metabolism by gut microbial communities in a diet-specific manner. Results demonstrated that SDF-diets could reduce TMA and trimethylamine N-oxide (TMAO) metabolism by 40.6% and 62.6%, respectively. DF feeding, particularly fermented SDF, reshaped gut microbial ecology and promoted the growth of certain beneficial microflora species. SDF-diet decreased energy intake, weight gain, intestinal pH values, and serum lipid and cholesterol levels. SDF-diet also enhanced the production of short chain fatty acids with activation of the intestinal epithelial adenosine monophosphate-activated protein kinase (AMPK).
Conclusions:
These findings suggest a central mechanism via which SDF-diet may control TMA metabolism by gut microflora and co-regulate the AMPK pathways of the host. This article is protected by copyright. All rights reserved.
High fat diet (HFD)-induced alterations in gut microbiota and resultant ‘leaky gut’ phenomenon promotes metabolic endotoxemia, ectopic fat deposition, and low-grade systemic inflammation. Here we evaluated the effects of a combination of green tea extract (GTE) with isomalto-oligosaccharide (IMOs) on HFD-induced alterations in mice. Male Swiss albino mice were fed with HFD (58% fat kcal) for 12 weeks. Systemic adiposity, gut derangement parameters and V3-V4 region based 16S rRNA metagenomic sequencing, ectopic fat deposition, liver metabolome analysis, systemic and tissue inflammation and energy homeostasis markers along with gene expression analysis were done in mice supplemented with GTE, IMOs or their combination. The combination of GTE and IMOs effectively prevented HFD-induced adiposity and lipid accumulation in liver and muscle while normalizing fasting blood glucose, insulin, glucagon, and leptin levels. Co-administration of GTE with IMOs effectively modulated liver metabolome associated with lipid metabolism. It also prevented leaky gut phenotype and HFD-induced increase in circulating lipopolysaccharides and pro-inflammatory cytokines (e.g. resistin, adiponectin, TNF-α, IL-1β, IL-6). Gene expression analysis across multiple tissues further supported these functional outcomes. Most importantly, this combination improved beneficial gut microbiota (Lactobacillus, Bifidobacteria, Akkermansia, Roseburia spp.) abundance and restored Firmicutes/Bacteriodetes and improved Prevotella/Bacteroides proportion. In particular, a combination of these two agents has shown improved beneficial effects on multiple parameters studied. Data presented herein suggests that strategically chosen food components might be highly effective in the prevention of HFD-induced alterations and may further be developed as functional foods.
Traditionally, obesity and its related diseases are considered problems in Western countries. However, in the past two decades, urbanization in many Asian countries has led to sedentary lifestyle and overnutrition, and has set the stage for the epidemic of obesity. This article reviews the epidemiological trend of obesity in Asia with special emphasis on the emerging condition of non-alcoholic fatty liver disease (NAFLD). Currently, the population prevalence of NAFLD in Asia is around 25%, similar to that in many Western countries. While hepatocellular carcinoma and end-stage liver disease secondary to NAFLD remain uncommon, a rising trend has recently been observed. Around 8-19% of Asians with body mass index less than 25 kg/m² are also found to have NAFLD, a condition often described as “lean” or “non-obese” NAFLD. Although the condition is generally less severe than that in more obese patients, steatohepatitis and fibrotic disease are well recognized in non-obese patients with NAFLD. Central adiposity, insulin resistance and weight gain are major risk factors, and genetic predisposition such as the PNPLA3 polymorphism appears to be more important in the development of NAFLD in the non-obese population. Lifestyle modification remains the cornerstone for the management of obesity and NAFLD, but few patients can achieve adequate weight reduction and even fewer can maintain the weight in the long run. While a few agents have entered phase 3 development for steatohepatitis, Asian patients are underrepresented in most drug trials. Future studies should define the optimal management of obesity and NAFLD in Asia.
The frequency of obesity is enormously growing worldwide .Obesity results when energy intake exceeds, energy expenditure. Excess adiposity is a major risk factor in the progress of various metabolic disorders accounting insulin resistance, hypertension, Type 2 diabetes, nonalcoholic fatty liver disease, polycystic ovarian disease and several types of cancers. Obesity is characterized by pro-inflammatory condition in which hypertrophied adipose tissue along with immune cells contribute to increase the level of pro-inflammatory cytokines. Immune cells are the key players in inducing low grade chronic inflammation in obesity and are main factor responsible for pathogenesis of insulin resistance resulting type 2 diabetes. The current review is aimed to investigate the mechanism of pro-inflammatory responses and insulin resistance involving immune cells and their products in obesity.