High Calorie Diet and the Human Brain: Metabolic Consequences of Long-Term Consumption
Abstract
The purpose of this monograph is to present readers with a comprehensive and cutting edge description of neurochemical effects of diet (beneficial and harmful effects) in normal human brain and to discuss how present day diet promotes pathogenesis of stroke, AD, PD, and depression in a manner that is useful not only to students and teachers but also to researchers, dietitians, nutritionists and physicians. A diet in sufficient amount and appropriate macronutrients is essential for optimal health of human body tissues. In brain, over-nutrition, particularly with high-calorie diet, not only alters cellular homeostasis, but also results in changes in the intensity of signal transduction processes in reward centers of the brain resulting in food addiction. Over-nutrition produces detrimental effects on human health in general and brain health in particular because it chronically increases the systemic and brain inflammation and oxidative stress along with induction of insulin resistance and leptin resistance in the brain as well as visceral organs. Onset of chronic inflammation and oxidative stress not only leads to obesity and heart disease, but also promotes type II diabetes and metabolic syndrome, which are risk factors for both acute neural trauma (stroke) and chronic age-related neurodegenerative and neuropsychological disorders, such as Alzheimer disease (AD), Parkinson disease (PD) and depression.
Chapters (10)
Long term consumption of high calorie diet, which is enriched in high amounts of saturated fats, cholesterol, n-6 fatty acids, salt and low fibers produces obesity, insulin resistance, type-2 diabetes, and metabolic syndrome. This pathological condition is an important risk factor for heart disease, stroke, Alzheimer disease, and cancer. At the molecular level, the long term consumption of high calorie diet not only promotes oxidative stress through induction of mitochondrial dysfunction, but also through decreased activities of antioxidant enzymes such as superoxide dismutase, catalase, and glutathione peroxidase. Long term consumption of high calorie diet also produces neuroinflammation through the generation of proinflammatory eicosanoids and increased expression of proinflammatory cytokines. In addition, long term consumption of high calorie diet is associated with endocrine disturbances and abnormalities in cardiac function supporting the view that long term consumption of high calorie diet impairs systemic metabolic homeostasis, which is a metabolic stressor associated with oxidative and endoplasmic reticulum stress. In contrast, calorie restriction with adequate micronutrient supplementation promotes metabolic fitness, longevity, and disease protection in rodents. Mediators of caloric restriction, including growth hormone, insulin, insulin-like growth factor-1, the circulating longevity hormone (Klotho) that binds to the IGF-1 receptor, as well as the Sirtuin family of longevity genes, have been shown to modulate both organismal lifespan and healthspan across species.
Long term consumption of high fat diet induces alterations in hypothalamus and hippocampal signaling leading to neuroinflammation and oxidative stress. High fat diet-mediated alterations in hypothalamus and hippocampal signaling involve ER stress and mitochondrial dysfunctions, and insulin resistance. Several mechanisms may contribute to high fat diet-mediated inflammation in hypothalamus and peripheral tissues. These mechanisms include the activation of TLR4 receptors, induction of ER stress, and activation of IKKβ. The relative contribution of these mechanisms in the induction of hypothalamic and peripheral inflammation remains unknown. However, early onset of inflammation in the hypothalamus relative to that in peripheral tissues suggests that different processes may cause inflammation in the peripheral tissues and hypothalamus. At the molecular level, inflammation is not only supported by elevation in levels of ARA and its lipid mediators (PGs, LTs, and TXs) and increase in platelet activating factor, but also with increase in expression of proinflammatory genes including genes for cytokines (TNF-α, IL-1β, and IL-6) along with activation of proinflammatory enzymes (secretory phospholipase A2, cyclooxygenase-2, and nitric oxide synthase). High fat diet is a major cause of obesity which is closely linked to a variety of health issues, including coronary heart disease, stroke, high blood pressure, fatty liver disease, diabetes, certain cancers, and neurological disorders. The consumption of high fat diet not only produces free radicals, but also contributes to the development of systemic inflammation and insulin resistance through the involvement of lipid-sense nuclear factors such as peroxisome proliferator-activated receptors (PPARs) and liver X receptors, which play critical roles in cellular fatty acid and carbohydrate metabolism as well as cell proliferation. High fat-mediated changes in hippocampus have negative impact on cognitive function not only due to vascular defects and impaired insulin metabolism, but also due to the defect in glucose transport mechanisms in brain.
The consumption of high carbohydrate diet produces many changes in the brain including alterations in electrophysiological properties of neurons, reduction in the density of synaptic inputs, induction of gliosis and impairment in insulin signaling in hypothalamic neurons controlling energy balance. In the liver, fructose is metabolized by fructokinase, which is not regulated by the negative feedback mechanism. Utilization of ATP in fructokinase reaction results in intracellular phosphate depletion and the rapid generation of uric acid due to activation of AMP deaminase. The consumption of fructose in high calorie diet correlates closely with the rise in insulin resistance, obesity, diabetes as well as neurological disorders. Fructose is a highly lipogenic sugar. It stimulates triglyceride synthesis, and increases fat deposition in the liver. The consumption of fructose also produces oxidative stress and mitochondrial dysfunction, resulting into stimulation of peroxisome proliferator-activated receptor gamma coactivator 1-α and β (PGC1-α and PGC-1β) that drive both insulin resistance and lipogenesis. Fructose-mediated uric acid generation not only contributes to hypertension, but is also linked with endothelial dysfunction, and insulin and leptin resistance.
Short term consumption of high protein diet has been reported to cause weight loss and prevention of weight (re)gain. High protein diet not only induces satiety, increases secretion of gastrointestinal hormones, and increases diet-mediated thermogenesis, but also induces adaptations of the metabolic pathways involved in protein and energy metabolism. Depending on amino acid composition, rate of absorption, and protein/food texture, consumption of proteins produce unique effects in visceral tissues and brain. These characteristics may modulate and determine the metabolic effects of proteins in the visceral tissues and brain. However, long term consumption of high-protein diets may produce detrimental effects on human health. High levels of isoleucine, leucine, valine, tyrosine, and phenylalanine produce insulin resistance and markedly increase the risk of diabetes, cardiovascular disease, and chronic kidney disease.
The consumption of artificial sweeteners is very popular because they are low in calories. Although, Food and Drug Administration has approved aspartame, acesulfame-k, neotame, cyclamate and alitame for use as per acceptable daily intake value, but it is becoming increasingly evident that breakdown products of these sweeteners may produce harmful metabolic effects in the visceral tissues and brain. Thus, aspartame is hydrolyzed into phenylalanine, aspartic acid, and methanol. Phenylalanine regulates neurotransmitters, whereas aspartic acid plays an important role in inducing excitotoxicity in the brain. Lastly methanol is oxidized into formaldehyde and diketopiperazine, a carcinogen, which mediates a number of other highly toxic effects. In experimental rats saccharin is known to cause bladder cancer. Steviol, a natural extract from the Stevia plant is a mutagen, but the safety of steviol glycoside as well as steviol oxidatives has been proven. Sucralose (Splenda™) is chlorinated sucrose, which is 600 times sweeter than sucrose. Sucralose has been reported to cause dizziness, head and muscle aches, stomach cramps, diarrhea, chronic inflammation and bladder issues in rodents and humans. So far studies performed on the safety of artificial sweeteners have been a major concerned due to their neurological effects and cancer-related issues.
Sodium in diet is a major contributor to high BP, but effect of salt on BP depends on genetic makeup. This is because salt sensitivity is largely determined by several genes, one of which is the ACE gene. The renin–angiotensin aldosterone systems (RAAS) play a major role in the pathogenesis of high BP, which is a risk factor for coronary events, stroke, kidney failure, kidney stones and heart failure. By contrast, inadequate salt intake may lead to fatigue, postural hypotension, and insulin resistance. It is advised that most patients should use salt in moderation; i.e., to avoid high-sodium foods and not to add large amounts of salt to food during cooking or at the table. The kallikrein-kinin system (KKS) also contributes to the modulation of BP. It is hypothesized that the disruption of the RAAS/KKS balance may provoke increase in BP. In addition, endothelial dysfunction is another hallmark of high BP. It reflects the premature aging of the intima exposed to the chronic increase in arterial BP. It is caused by complex changes in the balance between endothelium-dependent vasodilator and vasoconstrictor signals. Levels of released NO and the generation of vasoconstrictor eicosanoids contribute to endothelial dysfunction. RAAS-mediated changes in brain may contribute to the pathogenesis of neurological disorders. Thus, high BP may increase the risk of microvascular brain damage and impairment in mobility, cognition, and mood. Loss of cognitive function is one the most devastating manifestations of changes in BP and vascular disease. High BP is known to cause cerebral small and large vessel disease resulting in brain damage and dementia.
Dietary fiber is the non-digestible form of carbohydrates and lignin. Consumption of high fiber diet produces beneficial effects on human health through many potential mechanisms. Thus, dietary fiber not only increases fecal bulking and viscosity, but also decreases contact time between potential carcinogens and mucosal cells. In addition, dietary fiber not only increases the binding between bile acids and carcinogens, but also promotes healthy lipid profiles, glucose tolerance, and ensures normal gastrointestinal function. In addition, dietary fiber is a substrate for fermentation by microbiota found in the rectum. Microbiota produce SCFAs (acetate, propionate, and butyrate), which are readily absorbed. Butyrate is the major energy source for colonocytes. Propionate is largely taken up by the liver. Acetate enters the peripheral circulation to be metabolized by peripheral tissues. In colonic mucosa, butyrate promotes prevention of colon cancer by inducing cell differentiation, cell-cycle arrest and apoptosis of transformed colonocytes. Collective evidence suggests that increase in SCFA production, specifically butyrate in distal colon may result in a protective effect. Collective evidence suggests that dietary fiber improves laxation, increases excretion of bile acid, estrogen, and fecal procarcinogens and carcinogens, lowers serum cholesterol, slows glucose absorption and improves insulin sensitivity. The consumption of fiber also lowers blood pressure, promotes weight loss, inhibits lipid peroxidation; and produces anti-inflammatory effects.
Long term consumption of high calorie diet, which is enriched in saturated fats, cholesterol, and n-6 fatty acids, has been reported to not only cause the synthesis of proinflammatory lipid mediators (eicosanoids and platelet activating factor), proinflammatory cytokines (TNF-α, IL-1β, and IL-6), but also reported to upregulate the expression of gp91(phox) subunit of NADPH oxidase, and downregulates superoxide dismutase (SOD) and other detoxifying enzymes. High calorie diet consumption-mediated biochemical changes produce oxidative stress, and low grade inflammation. These processes promote weight gain, obesity and insulin resistance leading to type 2 diabetes and metabolic syndrome, a pathological condition, which is an important risk factor for cardiovascular disease, osteoporosis, arthritis, and various types of cancers.
Long-term consumption of high calorie diet, which is enriched in saturated fats, cholesterol, and n-6 fatty acids produces obesity, insulin resistance, oxidative stress, low grade inflammation, and cognitive dysfunction due to abnormalities in mitochondrial function and marked alterations in signal transduction processes. High calorie diet also alters hippocampal morphology/plasticity leading to the impairment of cognitive function in rodents. This brain region is involved in learning and memory formation. Accumulating evidence suggests that long term consumption of high calorie diet not only causes oxidative stress through multiple biochemical mechanisms, but also promotes low grade chronic inflammation through increased expression of proinflammatory cytokines. Onset of chronic inflammation and oxidative stress promotes type 2 diabetes, and metabolic syndrome, which are risk factors for stroke, Alzheimer disease, and depression. In addition, long term consumption of high calorie diet also suppresses adaptive cellular response signaling by inhibiting expression of neurotrophic factors, protein chaperons, DNA-repair proteins, autophagy, and mitochondrial biogenesis.
Diet patterns modulate the onset and pathogenesis of metabolic and age-related chronic neurological disorders. Thus, long term consumption of high calorie diet with high saturated fat, cholesterol, high levels of n-6 fatty acids, high levels of refined carbohydrates, and high salt produces chronic oxidative stress and inflammation which are characterized by over production of ROS, AGE, eicosanoids, and proinflammatory cytokines along with declines in antioxidant capacity in visceral tissues and the brain. These processes not only contribute to cognitive decline, but also neurodegeneration. In contrast, Mediterranean diet with low saturated fats and low refined sugars, but rich in olive oil, n-3 fatty acids, antioxidants vitamins C, E, and polyphenolic compounds produces neuroprotective effects supporting the view that specific dietary constituents of Mediterranean diet are able to influence the onset and development of above mentioned metabolic and neurological disorders. Similarly, the consumption of ketogenic diet retards obesity, metabolic syndrome, and diabetes as well as epilepsy amyotrophic lateral sclerosis, Alzheimer, Parkinson’s disease, and some mitochondriopathies. These diseases have different pathogenesis and features, but oxidative stress and neuroinflammation are closely associated with the pathogenesis of above mentioned diseases.
... With the aid of an ultratome (Reichert Ultracut, Ziess, Germany), ultrathin sections 70-90 nm thickness and stained with lead citrate and uranyle acetate were cut. They were then examined and captured on camera using a transmission electron microscope (Mycotic Centre, Al-Azhar university) [16] Morphometric analysis: Using ImageJ (version 1.33-1.34; National Institutes of Health, Bethesda, MD, USA), the following parameters were assessed [17]: GFAP immune-stained sections' field integrated density (IntDen). ...
... DISCUSSION Aspartame, sucralose, saccharin, acesulfame-K, and neotame are five commonly used artificial sweeteners that have received FDA approval. Apart from the herbal extract, stevia, and the sugary alcohol erythritol, which have limited applications, [16]. Among these sweeteners, over 90 countries and 6,000 products use aspartame more frequently than any other synthetic nonnutritive sweetener. ...
... The impaired function of EPCs may be restored by improving their mobilization e.g., by statins, vascular endothelial growth factor (VEGF), estrogen, or by drugs that improve function leading to the self-repair of damaged capillaries in the diabetic retina (Caballero et al., 2007) Increased production of Advanced Glycation Endproducts (AGE) AGE compounds are formed by a highly reactive, non-enzymatic reaction between reducing sugars and proteins/lipids/nucleic acids. AGE compounds diffuse out of the cell and cause modification of ECM molecules leading to cellular dysfunction (Charonis et al., 1990;Farooqui, 2015). AGE compounds also modify intracellular proteins, change their structure, cross-linking, enzymatic activity, receptor recognition and impair their clearance. ...
... However, isolated studies have demonstrated the age dependent accumulation of AGE in vascular beds and lens in an animal model (Georgescu and Popov, 2000). AGE induce apoptosis in retinal pericytes by activation of transcription factors like FOXO1, mediated by p38 and JNK MAP Kinases (Curtis et al., 2009;Alikhani et al., 2010;Stirban et al., 2014;Farooqui, 2015). Moreover, inhibition of formation of AGE has also been found to reduce the progression of DR (Kern and Engerman, 2001;Stitt et al., 2002;Bhatwadekar et al., 2008;Thallas-Bonke et al., 2008). ...
Vasoregression is a common phenomenon underlying physiological vessel development as well as pathological microvascular diseases leading to peripheral neuropathy, nephropathy, and vascular oculopathies. In this review, we describe the hallmarks and pathways of vasoregression. We argue here that there is a parallel between characteristic features of vasoregression in the ocular microvessels and atherosclerosis in the larger vessels. Shared molecular pathways and molecular effectors in the two conditions are outlined, thus highlighting the possible systemic causes of local vascular diseases. Our review gives us a system-wide insight into factors leading to multiple synchronous vascular diseases. Because shared molecular pathways might usefully address the diagnostic and therapeutic needs of multiple common complex diseases, the literature analysis presented here is of broad interest to readership in integrative biology, rational drug development and systems medicine.
... This generates a new homeostatic alternation and thereby brings epigenetic changes in the neuroendocrine genes with the production of proinflammatory cytokines. On the other hand, NF-kB induced iNOS, COX-2 and inflammatory cytokine production that paves the way to the anti-inflammatory activity [49,63,64]. Studies show that the concentration of cytokines such as IL-1α, IL-1β, IL-6 and type B receptor IL-8 (IL-8RB) is elevated close to the sites where amyloid plaques are located. ...
Alzheimer’s disease (AD) is a neurodegenerative disease with rapid progression. Black cumin (Nigella sativa) is a nutraceutical that has been investigated as a prophylactic and therapeutic agent for this disease due to its ability to prevent or retard the progression of neurodegeneration. Thymoquinone (TQ) is the main bioactive compound isolated from the seeds of black cumin. Several reports have shown that it has promising potential in the prevention and treatment of AD due to its significant antioxidative, anti-inflammatory, and antiapoptotic properties along with several other mechanisms that target the altered signaling pathways due to the disease pathogenesis. In addition, it shows anticholinesterase activity and prevents α-synuclein induced synaptic damage. The aim of this review is to summarize the potential aspects and mechanisms by which TQ imparts its action in AD.
... The brain's reward and motivational system, in part, seems to drive for the optimization of sufficient calories for the survival of humans (Farooqui, 2015). The ingredients of calorie-dense such as sugar, fat contents play an effective role both in the stimulation of reward and motivation systems, and endogenous opioid and mesolimbic dopaminergic pathways in the brain (Berridge et al., 2010). ...
This review aims to draw attention to current studies on syndromes related to food eating behavior, including food addiction, and to highlight the neurobiological and neuropharmacological aspects of food addiction toward the development of new therapies. Food addiction and eating disorders are influenced by several neurobiological factors. Changes in feeding behavior, food addiction, and its pharmacological therapy are related to complex neurobiological processes in the brain. Thus, it is not surprising that there is inconsistency among various individual studies. In this review, we assessed literature including both experimental and clinical studies regarding food addiction as a feeding disorder. We selected articles from animal studies, randomized clinical trials, meta-analyses, narrative, and systemic reviews given that, crucial quantitative data with a measure of neurobiological, neuropharmacological aspects and current therapies of food addiction as an outcome. Thus, the main goal to outline here is to investigate and discuss the association between the brain reward system and feeding behavior in the frame of food addiction in the light of current literature.
... The older age, unhealthy lifestyle, toxic environment exposure, high fat diet and family history are several risk factors for AD. [28] Hyperphosphorylated tau hypothesis: ...
... Nutrition habits do not only produce healthy effects but also modulate the onset and pathogenesis of metabolic diseases (obesity, type II diabetes and metabolic syndrome), age-related acute and chronic neurological disorders (Stroke, Alzheimer's disease and depression). 3 Diet high in fructose produces hepatic steatosis (the accumulation of triglycerides in the liver) and lipogenesis, which results in the impairment of lipid metabolism (hyperlipidemia). These effects contribute to weight gain, obesity and the enhancement of the expression of pro-inflammatory cytokines. ...
Introduction: Obesity is a public health problem that is associated with cerebrovascular diseases, such as ischemic stroke. The coexistence of obesity with cerebral ischemia has been suggested to be considerably detrimental to the neurological system. Objective: Hence, in this study, we evaluated the long-term effects of a 20% high fructose diet (HFD) and global cerebral ischemia on neurological, cognitive and emotional performance in three-month-old male Wistar rats. Results: Our results demonstrated that fructose intake led to increases in body weight and blood glucose, as well as reduced insulin sensitivity. The co-morbidity of fructose intake and cerebral ischemia resulted to hyperlipidemia, as well as increases in liver and adipocyte damage, which worsened neurological performance and resulted in alterations in learning and emotional skills at two weeks post-ischemia. No significant biochemical changes in autophagy and plasticity markers at the late stage of ischemia were observed. Conclusion: These results suggested that obesity causes a lasting effect on metabolic disorders that can contribute to increased neurological impairment after cerebral ischemia.
... High calorie diets, rich in carbohydrates, saturated fats and cholesterol have been shown to be associated with metabolic dysregulation, increased oxidative stress and increased inflammation which are all risk factors for obesity, cardiovascular disease, metabolic disorders, arthritis and various cancers. 31 There are limited studies however on the effects of nutrition on multimorbidity. A cross-sectional study found that that individuals with high consumption of a "meat and potatoes" diet had greater likelihood of cardiometabolic morbidity, with obesity as a likely intermediate step. ...
Multimorbidity is a global health challenge. Here, we define multimorbidity, describe ways multimorbidity is measured, discuss the prevalence of multimorbidity and how it differs across different populations, examine mechanisms of disease and disability, and discuss the effects of multimorbidity on outcomes such as survival and function.
... Rahn et al. [46] found that sucralose can degrade and produce chloropropanols (3-monochloropropanediol and 1,2-and 1,3-dichloropropanols) under thermal decomposition. These metabolites are known as a potentially toxic class of compounds that may cause cancer [47]. Another study indicated that ingestion of sucralose may affect the glucose metabolism of obese people who rarely use nonnutritive sweeteners [48]. ...
Background
The vast occurrence of organic micropollutants in surface waters has raised concerns about drinking water safety and public health. The Tai Hu Basin region in China, a typical developing and populous area, is facing the challenge of water pollution. To ensure drinking water safety, the knowledge on how treatment techniques and raw water quality affect the quality of finished water must be improved. The aim of the current study was to evaluate drinking water quality with respect to organic micropollutants and how the purity of the finished water depends on source water contamination and drinking water treatment strategies. Five drinking water treatment plants (DWTPs), using three different source waters in the Tai Hu River Basin, (i) Yangtze River, (ii) Wetland River Network, and (iii) Lake Tai Hu, were studied by analyzing 291 micropollutants in raw and finished water.
Results
Major differences in concentrations and composition profiles of organic micropollutants were observed between the source waters. Among the studied micropollutants, the dominating group was pesticides in the Wetland River Network and flame retardants in Yangtze. The total concentration of poly- and perfluoroalkyl substances (PFASs) in Tai Hu water was far higher than in the other samples. In total, 51 compounds were detected in the finished water, with an overall average total concentration of 730 ± 160 ng L⁻¹. The removal efficiency of the detected compounds in the DWTPs averaged 24 ± 150%, which highlights the major challenge for the DWTPs in removing the emerging organic micropollutants through current treatment processes.
Conclusions
Our study showed that if the source water contains high levels of PFASs and organophosphorus flame retardants, even advanced treatment procedures are inefficient in removing the micropollutants, and the finished drinking water may contain cumulative levels of organic micropollutants in the µg L⁻¹ range. On the other hand, if pesticides and pharmaceuticals dominate, a high overall treatment efficiencies may be obtained if advanced treatment techniques are used. The DWTPs are advised to use advanced treatment techniques or alternative water sources to guarantee the safety of drinking water. As surface water systems are highly impacted by upstream activities, efforts should also be made in the water sector for improving the surface water quality.
... It was earlier reported that dysfunction of FASN driven lipogenesis is the common link in insulin resistance type -2 diabetes and insulin resistance metabolic disorder including cancer 10,11 . Wang et al 12 also discussed the key role of FASN in the association between obesity and cancer. ...
The world population is at major risk of obesity and overweight, leading to various chronic implications at later stages like cardiovascular diseases, diabetes and sometimes cancers. The fatty acid synthase (FASN) protein plays key role in fatty acid synthesis by interacting with Acetyl CoA. It also works in close association with various genes that are involved in number of metabolic processes. The Ganoderma mushrooms were found abundant in nature with ganoderic acid variants having potential activity in number of biological pathways. Ganoderic acid and its effects on FASN protein by docking and finding its influence through genetic networks have been investigated in the present study. By docking studies, with variants of ganoderic acid we found that (a) the binding affinity specially ganoderic AP3 is very high towards FASN protein as compared to its natural substrate Acetyl CoA and (b) ganoderic acid may act as competitive inhibitor for FASN protein having potential to work better than synthetic molecules. It is further observed by network analysis that by targeting FASN protein by ganoderic acid, various biological processes like lipid synthesis, coenzyme metabolic, glycerolipid metabolism, neutral lipid metabolism can be modulated.
The fruit processing industry is responsible for disposing of huge amounts of byproducts, especially fruit peels (FPs), which are often discarded in landfills. Using FPs in biotechnological processes contributes to a circular economy, reducing the environmental burden of FPs and increasing the revenue of the fruit processing industry. This study was focused on upgrading the nutritional value of orange (OPs) and banana (BPs) peels by solid-state fermentation (SSF) with filamentous fungi. SSF factors (moisture, fermentation time, inoculum size, ammonium sulfate (AS), and corn steep liquor (CSL)) and fungi species (Aspergillus ibericus and Rhizopus oryzae) were studied by a variable screening Plackett–Burman design. Both fungi grew on untreated FPs, increasing their protein content and antioxidant activity. Moisture, AS, and CSL were further studied by a Box–Behnken design with A. ibericus. Fermented OPs at 70% moisture and 0.005 g/g AS increased their protein content by 200%, whereas BPs at 70% moisture and 0.005 g/g CSL increased by 123%. Fermented peels were enriched in protein, fiber, and minerals, with a low content of carbohydrates and soluble sugars. Fermented OPs and BPs showed higher antioxidant activity than unfermented peels. The SSF of these FPs is an innovative approach that contributes to obtaining rich nutrient-fermented peels for food.
Intervention with natural products is becoming a promising obesity control strategy as healthy eating becomes increasingly popular. The present study aimed to prepare a citrus-based functional jelly (CFJ) from citrus by-products and investigate its bioactive effects in mice. The results of the CFJ preparation showed that the optimal formula of CFJ was 29.12%, 20%, and 3.61% for chenpi, orange juice, and pectin, respectively. The optimized CFJ can be personalized and designed with jelly shapes using 3D food printing technology. The evaluation of the biological activity of the CFJ showed that it was low in calories, with a total phenolic content of 12.44 ± 0.26 mg GAE/g. Moreover, the CFJ has a good free radical scavenging ability for ABTS. The results of the mouse experiments showed that the CFJ significantly suppressed the body weight gain and fat deposits with a dose-dependent effect, compared with the control group (p < 0.05). In addition, the activities of the antioxidant-related enzymes (CAT and SOD) of the mice were also enhanced after a supplementation with the CFJ. In short, the CFJ is a functional snack enriched in phenolic substances with low-calorie, antioxidant and anti-obesity properties. This work promotes the utilization of citrus by-products and the healthy development of its processing industry.
Objectives
Cerebral ischemia is the most common cause of disability, the second most common cause of dementia, and the fourth most common cause of death in the developed world [Sveinsson OA, Kjartansson O, Valdimarsson EM. Heilablóðþurrð/heiladrep: Faraldsfræði, orsakir og einkenni [Cerebral ischemia/infarction - epidemiology, causes and symptoms]. Laeknabladid. 2014 May;100(5):271–9. Icelandic. doi:10.17992/lbl.2014.05.543]. Obesity has been associated with worse outcomes after ischemia in rats, triggering proinflammatory cytokine production related to the brain microvasculature. The way obesity triggers these effects remains mostly unknown. Therefore, the aim of this study was to elucidate the cellular mechanisms of damage triggered by obesity in the context of cerebral ischemia.
Methods
We used a rat model of obesity induced by a 20% high fructose diet (HFD) and evaluated peripheral alterations in plasma (lipid and cytokine profiles). Then, we performed cerebral ischemia surgery using two-vessel occlusion (2VO) and analyzed neurological/motor performance and glial activation. Next, we treated endothelial cell line cultures with glutamate in vitro to simulate an excitotoxic environment, and we added 20% plasma from obese rats. Subsequently, we isolated EVs released from endothelial cells and treated primary cultures of astrocytes with them.
Results
Rats fed a HFD had an increased BMI with dyslipidemia and high levels of proinflammatory cytokines. Glia from the obese rats exhibited altered morphology, suggesting hyperreactivity related to neurological and motor deficits. Plasma from obese rats induced activation of endothelial cells, increasing proinflammatory signals and releasing more EVs. Similarly, these EVs caused an increase in NF-κB and astrocyte cytotoxicity. Together, the results suggest that obesity activates proinflammatory signals in endothelial cells, resulting in the release of EVs that simultaneously contribute to astrocyte activation.
Atherosclerosis is a complex inflammatory disease characterized by lipid accumulation within the artery walls. It produces the narrowing of arteries due to the development of intimal plaques. The formation of plaques involves the deposition of small cholesterol crystals in the intima and its underlying smooth muscle. The growth of plaques starts with the proliferation of fibrous tissues and the surrounding smooth muscle producing a bulge inside the arteries. It results in reduction of the blood flow to the heart leading to cardiovascular disease, the leading cause of mortality and morbidity worldwide. Atherosclerosis and cardiovascular disease are not only accompanied by increased levels of cholesterol, cholesterol metabolites, and trimethylamine N-oxide levels in the blood, but also by the involvement of the immune system, which is made up of many cell types, hundreds of bioactive cytokines and chemokines (TNF-α, IL-1β, IL-6, MCP-1), and millions of different antigens. This makes the development of atherosclerosis very challenging. In addition to the development of myocardial infarctions, atherosclerosis is also associated with peripheral artery disease. This pathological condition is also accompanied by different stages of atherogenesis, dyslipidemia, hypertension, oxidative stress, endothelial dysfunction, and inflammation. At the molecular level, these processes involve the generation of reactive oxygen species, reduction in redox status, and increased expression of pro-inflammatory cytokines and chemokines. These mediators can be used as biomarkers for cardiovascular disease, as well as peripheral artery disease.
Cookies, which form the largest category of bakery snacks, are considered a good vehicle to introduce nutrients into the diet. In this study, to increase the nutritional value of traditional commercial cookies, wheat flour was substituted with defatted flours made from flax, sesame, chia, and poppy, which are byproducts of the oil extraction industry. The differences in the technological properties, nutritional composition, and consumer acceptance of the reformulated cookies were evaluated. The results show that the wheat cookies used as the control showed a more elastic behavior than the cookies elaborated with defatted seed flours, which showed a greater tendency to crumble. The use of defatted seed flours yielded cookies with a higher content of protein and fiber, and a lower content in carbohydrates than the wheat cookies. Consumer evaluations for the sesame and flax cookies were similar to those for the traditional wheat cookies, with positive assessments on all of the parameters evaluated. On the other hand, the cookies elaborated using chia and poppy flours received the least positive evaluations from consumers. Thus, the use of some defatted seed flours, mainly flax and sesame, is proposed as an interesting alternative to produce health-promoting cookies in order to cover the current demand for gluten-free products.
This research determined the antioxidant activities of medicinal plants fermented by Enterococcus faecium and their subsequent applications as dog food additives. Turmeric (5%, w/v), glasswort (2.5%, w/v), Ganghwa mugwort (2.5%, w/v), and their mixture (5%, w/v) were fermented by autochthonous E. faecium (1%, v/v) for 72 h. Bacterial cell counts and pH were monitored during fermentation. Total polyphenol content (TPC), total flavonoid content (TFC), 2,2′-azino-bis (3-ethylbenzothiazoline-6-sulfonic acid) (ABTS) and 1,1-diphenyl-2-picrylhydrazyl (DPPH) radical scavenging activity, and intracellular superoxide scavenging activity in bovine mammary alveolar epithelial (MAC-T) cells were measured with the fermented and non-fermented samples. Only the antioxidant capacity of the mixture was increased after fermentation. However, intracellular superoxide level in MAC-T cells was significantly reduced after treatment with fermented plant samples (p < 0.001) as compared with that in non-fermented plants. Fermented plants were then sprayed at 1% (v/w) onto dog foods. TPC, TFC, ABTS radical scavenging activity, and DPPH radical scavenging activity of dog foods were significantly enhanced after the addition of fermented plants. Food preference testing was conducted using a two-pan method—control diet vs. four treatment diets—for 4 days for each additive diet, a total 16 days in 9 beagles. Feces were collected to enumerate bacterial counts. Preferences for glasswort and Ganghwa mugwort were higher than those of the control (p < 0.05). Furthermore, fecal microbiota enumeration displayed a higher number of beneficial microorganisms in treated groups. These results suggest that fermented plants with enhanced antioxidant abilities might be useful as potential additives for dog foods.
Mediterranean diet consists of fresh fruits, vegetables, legumes, whole grains, fish, olive oil, garlic, and red wine. Levels of saturated fats are very low in Mediterranean diet. Among Mediterranean diet components, fresh fruits and vegetables provide various vitamins, carotenoids, flavonoids, fiber, and metal ions (potassium, magnesium, and calcium). Fish provides eicosapentaenoic and docosahexaenoic acids; olive oil is enriched in polyphenols (tyrosol, hydroxytyrosol, and oleuropein); red wine contains resveratrol; and garlic is enriched in sulfur compounds (alliin, allicin, S-allyl cysteine, and diallyl trisulfide). High levels of free radicals and neuroinflammation play an important role in cardiovascular diseases, type 2 diabetes, and neurological disorders. Mediterranean diet-derived metabolites are known to block free radical damage and retard neuroinflammation in above pathological conditions. Collectively, these studies indicate that the consumption of Mediterranean diet from the childhood to the old age not only leads to decrease in cardiovascular diseases, type 2 diabetes, and many types of cancers but also slows the onset of neurological disorders.
It is well known that curcumin produces antioxidant, anti-inflammatory, anticancer, antiviral, and antiarthritic properties. The poor bioavailability of curcumin is the major hurdle for its more widespread use in animals and humans. However, complexation and encapsulation of curcumin into liposomes, cyclodextrin, curcumin conjugate with PLGA, complexation with phospholipids, and synthesis of curcumin analogs have made it easy to bypass this problem. New ways of delivering curcumin have resulted in increased absorption and delivery of curcumin to various body tissues including brain. The underlying mechanisms of these effects are diverse and appear to involve the regulation of various molecular targets, including transcription factors (NF-κB and HIF-1), growth factors (vascular endothelial cell growth factor), inflammatory cytokines (TNF-α, IL1, and IL-6), and enzymes (protein kinases (MAPK, Akt, COX-2, and 5-LOX).
Alzheimer disease (AD) is recognized as one of the most common causes of dementia that leads to impairment of memory, thinking and behavior in humans. The major pathological features of AD are the increased production and deposition of amyloid-β (Aβ) and intracellular accumulation of neurofibrillary tangle composed of hyperphosphorylated tau protein, besides mitochondrial dysfunction, oxidative stress, neuroinflammation, and loss of synapse and neuronal. The animal modeling of AD has been performed in invertebrates and vertebrates. The modeling has been pursued on the basis of the amyloid hypothesis and has taken advantage of mutations in the APP, MAPT, PS1, PS2 tau protein and apoE genes, which are involved in familial forms of AD. Genetic modification technology is well developed in mice. Many transgenic mouse models have been developed. These models mimic a range of AD–related neurochemistry and pathology. Although none of the models fully replicates the human disease, the models have contributed significant insights into the pathophysiology of β-amyloid toxicity, particularly with respect to the effects of different β-amyloid species and the possible pathogenic role of β-amyloid oligomers. They have also been widely used in the preclinical testing of potential therapeutic modalities and have played a pivotal role in the development of immunotherapies for AD. There is a need for developing better animal models in bigger animals, such as rats for developing better biomarkers and drug testing information.
Neuroinflammation is a well coordinated and protective mechanism, which is characterized by redness, pain, swelling and temperature. Low neuroinflammation for a short duration produces neuroprotective effects in the brain, but both acute and long term chronic neuroinflammation produces neurodegenerative effects. At the cellular level, neuroinflammation is accompanied by activation of microglia and astrocytes. At the molecular level, neuroinflammation is companied by the generation of high levels of PGs, LTs, and TXs and increased expression of TNF-α, IL-1β, IL-6 IL-8, CXC, and chemokine receptor 4 (CXCR4). These mediators along with ROS, and NO impair mitochondrial function by inducing the accumulation of mtDNA mutations and inhibiting mitochondrial respiratory chain and energy production. Neuroinflammation is an early event in the amyloid pathology and precedes plaque deposition in human subjects and experimental models of AD. Curcumin is an excellent antioxidant antiinflammatory agent. It can cross BBB and inhibits cyclooxygenase and lipoxygenase activities leading to decrease in generation of PGs, LTs, and TXs. It also inhibits the production of NO, TNF-α, and IL-1β. Curcumin mediates its beneficial effect not only by modulating APP processing and downregulating gene expression of proteins associated by apoptosis and neuroinflammation, but also by increasing Aβ uptake by macrophages. Curcumin also induces heat shock proteins and reduces protein misfolding and aggregation.
Curcumin mediates its neuroprotective effects not only in neurotraumatic disorders (stroke, spinal cord injury, traumatic brain injury, and epilepsy), but also in Parkinson disease, Huntington disease, and prion diseases. In addition, curcumin also promote its beneficial effects in neuropsychological disorders (depression, biopolar disorders, and tardive dyskinesia). The mechanism associated with neuroprotective action of curcumin is not fully understood. However, it is becoming increasingly evident that anti-inflammatory and antioxidant properties of curcumin may be responsible for neuroprotective effects. At the molecular level, neuroprotective effects of curcumin are accompanied by downregulating activities of phospholipases, lipooxygenase, cyclooxygenase-2, which lead to low levels of leukotrienes, thromboxanes, prostaglandins. In addition, curcumin also inhibits the expression of TNF-α, IL-12, MCP-1, and interferon-inducible protein. In addition, curcumin also modulates various neurotransmitter levels in the brain.
Alzheimer disease (AD) is a multifactorial disorder involving oxidative stress, neuroinflammation, impairments in energy metabolism, and excitotoxicity. AD affects several brain regions such as entorhinal cortex, hippocampus, basal forebrain and amygdale, which exhibit synaptic loss resulting in extensive brain atrophy. In vulnerable brain regions, AD is characterized by the accumulation of extracellular neuritic plaques and intracellular neurofibrillary tangles. The neurofibrillary tangles consist largely of hyperphosphorylated twisted filaments of the microtubule-associated protein Tau. Extracellular neuritic plaques are deposits of Aβ that are derived via sequential proteolytic cleavages of the APP. Clinically, AD patients present with symptoms of memory loss, altered personality and behavior, and impaired executive function. Neurochemically, AD is accompanied by profound biochemical alterations in multiple pathways including increased turnover of membrane phospholipid, sphingolipid, and cholesterol metabolism and increase in phospholipid-, sphingolipid-, and cholesterol-derived lipid mediators. The severity of AD pathology is associates with number of reactive astrocytes and activated microglia in the brain. Both neurons and glial cells contribute to the induction, maintenance, and progression of neuroinflammation and oxidative stress in AD by releasing proinflammatory cytokines and generating reactive oxygen and nitrogen species, which contribute to neurodegeneration in AD. Accumulating evidence suggests that AD also involves increases in metal ions (iron, copper, and zinc), nitric oxide generation, reduction in expression of trophic factors, dysfunction of the ubiquitin–proteasome system, depletion of endogenous antioxidants, and expression of proapoptotic proteins leading to synaptic and neuronal loss.
Intestinal dysbiosis is thought to be an important cause of disease progression and the gastrointestinal symptoms experienced in patients with inflammatory bowel disease (IBD). Inflammation appears to be a major contributor in perpetuating a dysregulated gut microbiota. Although current drug therapies can significantly induce and maintain disease remission, there is no cure for these diseases. Nevertheless, ongoing human studies investigating dietary fibre interventions may potentially prove to exert beneficial outcomes for IBD. Postulated mechanisms include direct interactions with the gut mucosa through immunomodulation, or indirectly through the microbiome. Component species of the microbiome may degrade dietary-fibre polysaccharides and ferment the products to form short-chain fatty acids such as butyrate. Prebiotic dietary fibres may also act more directly by altering the composition of the microbiome. Longer term benefits in reducing the risk of more aggressive disease or colorectal cancer may require other dietary fibre sources such as wheat bran or psyllium. By critically examining clinical trials that have used dietary fibre supplements or dietary patterns containing specific types or amounts of dietary fibres, it may be possible to assess whether varying the intake of specific dietary fibres may offer an efficient treatment for IBD patients.
The aim of this study was to investigate the effects of dietary fermentable fibre (Vitacel®) on haemato-immunological and serum biochemical parameters, intestinal histomorphology, growth performance and proximate body composition of rainbow trout (Oncorhynchus mykiss). One hundred and twenty fish (81.65 ± 1.49 g) were fed diets containing 0 and 10 g kg−1 fermentable fibre (Vitacel®) for 50 days. At the end of feeding trial, growth performance parameters were significantly improved in fermentable fibre (Vitacel®)-fed fish. Although feeding on fermentable fibre (Vitacel®)-supplemented diet had no remarkable effect on haematological parameters (RBC, Htc and Hb) (P > 0.05), white blood cell (WBC) count and monocyte level were significantly affected (P = 0.040 and P = 0.020, respectively). In case of serum biochemical parameters, a significant increase and decrease were observed in serum total protein (P = 0.040) and cholesterol level (P = 0.000), respectively. Also, lysozyme level was significantly increased following administration of Vitacel® in diet (P = 0.006). Histomorphological evaluations revealed that villus length (P = 0.004) and tunica muscularis thickness (P = 0.000) were significantly higher in fermentable fibre (Vitacel®)-fed fish. These results indicate that fermentable fibre can be considered as a dietary supplement for improving the health status and performance of rainbow trout.
Stevia rebaudiana, the sweet herb is commonly known as honey leaf in Indian market. Stevia is gaining significance in different parts of the world and is expected to develop into a major source of high potency sweetener for the growing natural food market. A thorough review has been made to visualize the contribution of different investigations on stevia. Extensive work has been done on its cultivation practices and other agro parameters have been identified for the sweetening potency. Stevia can be grown easily in pots, house gardens or as a commercial field crop. The plant is totally innocuous, posing no threat to human life and health, holding out in fact great hope of the production of a non calorie sweetener with health benefits. Published literature on the post-harvest practices of stevia leaf in India is limited. Stevia is the safest natural sweetener, and it can substitute sugar in various preparations and formulations. It has been used as a medicinal plant to treat many ailments including diabetes, high blood pressure, digestive disorders and several skin defects. The leaves contain glycosides, which taste sweet, but do not provide calories. The major glycoside is stevioside (10% of total glycoside), which accounts for its incredible sweetness.
This study tested whether rats with obesity induced by a hypercaloric diet (HD) present higher nutritional, endocrine, and cardiovascular disturbances compared with counterparts with obesity induced by overfeeding of a standard diet. An additional objective was to compare the isolated influence of HD on these parameters in lean and obese rats.
Twenty Wistar-Kyoto rats were distributed into four groups: CD-lean, CD-obese, HD-lean, and HD-obese. CD (control diet) and HD groups received commercial standard chow and HD, respectively, for 20 weeks. The lean and obese groups included obesity-resistant and obesity-prone animals, respectively. Nutritional and metabolic evaluation involved measurement of calorie intake, dietary efficiency, body weight, adiposity, glycemia, triacylglycerol, insulin, and leptin. Cardiovascular evaluation included systolic blood pressure measurement, echocardiography, and analyses of myocardial morphology and myosin heavy-chain composition.
In both diets, obesity was characterized by increased adiposity, hyperleptinemia, hypertriacylglycerolemia, hyperinsulinemia, and cardiomyocyte nuclear hypertrophy. HD promoted hyperleptinemia and cardiac remodeling, characterized by nuclear and ventricular hypertrophy, as well as improved systolic performance in both the obesity-prone and obesity-resistant biotypes. In contrast to HD-lean, HD-obese rats presented more accentuated endocrine responses, including hyperglycemia, lower glycemic tolerance, and hyperleptinemia as well as interstitial fibrosis compared with the CD-obese animals.
This study confirmed the primary hypothesis that rats with HD-induced obesity present more accentuated nutritional and endocrine disturbances compared with their counterparts with obesity resulting from overfeeding. In addition, dietary effects were more important between the obese groups, supporting evidence of an interaction between diet and biotype.
It has been argued that food cannot be "addictive", unlike conventional drugs of abuse, because it is an essential part of life. In this paper, evidence is reviewed, largely from an evolutionary psychobiological perspective, that plant-based psychoactive drugs (such as those derived from the opium poppy and the coca leaf) and gambling-related behaviors were once adaptive for human health and survival in a similar manner as energy-based foods were for nourishment. "Evolutionary mismatch" viewpoints contend that certain behaviors were enhanced during the hunter-gatherer lifestyle - from which our genetic endowment had its origins - because they bestowed both survival and reproductive advantages to the species. However, in the context of advanced technology and other rapid environmental changes, these same behaviors have tended to become maladaptive and greatly overexpressed. Similar to the manufactured purification of psychotropic plant-based substances, the reward impact of processed and hyperpalatable foods, with their high levels of sugar, fat, and salt, is much increased from foods produced in nature. It is concluded therefore that what was once beneficial and necessary for our survival has been altered and ultraprocessed into edible products that may be disadvantageous and potentially addictive.
Endothelial dysfunction and autonomic nervous system dysfunction are both risk factors for atherosclerosis. There is evidence demonstrating that there is a close interrelationship between these two systems. In hypertension, endothelial dysfunction affects the pathologic process through autonomic nervous pathways, and the pathophysiological process of autonomic neuropathy in diabetes mellitus is closely related with vascular function. However, detailed mechanisms of this interrelationship have not been clearly explained. In this review, we summarize findings concerning the interrelationship between vascular function and the autonomic nervous system from both experimental and clinical studies. The clarification of this interrelationship may provide more comprehensive risk stratification and a new effective therapeutic strategy against atherosclerosis.
The physiological expression of cytoprotective heat shock protein 27 (Hsp27) in the gut was investigated in eighteen 7-wk-old pigs fed one of 3 fiber-rich diets for 18 d. The diets were a cereal-based control diet and a cereal-based diet with inclusion of either 80 g/kg chicory forage (CF80) or chicory root (CR80). Immunohistochemical staining showed that Hsp27 was expressed in all the samples from ileum and colon. The expression was most intensive in the apical intestinal epitheliums in close contact with luminal contents and lighter in crypt cells. The ileal Peyer's patches showed a strong expression of Hsp27, which was highly correlated with Hsp27 expression in the ileal epithelial cells (P = 0.003). The frequency of ileal Hsp27 expression with the most intensive staining was distributed higher in pigs fed chicory forage diet (CF80, 25%) followed by chicory root diet (CR80, 16.7%) and the control (11.1%). In proximal colon, the frequency of expression showed a similar pattern for the different diets. The intestinal microbiota profile was characterized with the intention to find correlations to heat shock protein (Hsp) expression in pig gastrointestinal (GI) tract and showed that the distal ileum and proximal colon encompass its own unique microbial profile. However, no significant relationship was found between gut microbiota diversity and Hsp27 expression. These indicate that Hsp27 expression in the porcine gut could be associated with specific dietary fiber components but not the overall microbiota diversity.
It is acknowledged that the world is ageing at both the individual and population level. Life expectancies at birth have increased for males and females in the more developed economies across the 20th century. The 21st century is expected to see this development continue with life expectancies moving towards 100 years. This paper looks at the evidence for future increases in life expectancy and for the longest-lived to live even longer.
Background
It was the aim of the present systematic review and meta-analysis to investigate the effects of high protein (HP) versus normal/low protein (LP/NP) diets on parameters of renal function in subjects without chronic kidney disease.
Methods
Queries of literature were performed using the electronic databases MEDLINE, EMBASE, and the Cochrane Trial Register until 27th February 2014. Study specific weighted mean differences (MD) were pooled using a random effect model by the Cochrane software package Review Manager 5.1.
Findings
30 studies including 2160 subjects met the objectives and were included in the meta-analyses. HP regimens resulted in a significantly more pronounced increase in glomerular filtration rate [MD: 7.18 ml/min/1.73 m2, 95% CI 4.45 to 9.91, p<0.001], serum urea [MD: 1.75 mmol/l, 95% CI 1.13 to 237, p<0.001], and urinary calcium excretion [MD: 25.43 mg/24h, 95% CI 13.62 to 37.24, p<0.001] when compared to the respective LP/NP protocol.
Conclusion
HP diets were associated with increased GFR, serum urea, urinary calcium excretion, and serum concentrations of uric acid. In the light of the high risk of kidney disease among obese, weight reduction programs recommending HP diets especially from animal sources should be handled with caution.
Focal and segmental glomerulosclerosis (FSGS) is one of the most important renal diseases related to end stage renal failure. Bradykinin has been implicated in the pathogenesis of renal inflammation whereas the role of its receptor 2 (B2RBK) in FSGS has not been studied. FSGS was induced in wild type and B2RBK KO mice by a single intravenous injection of Adriamycin (ADM). In order to further modulate the kinin receptors, animals were also treated with B2RBK antagonist HOE-140, and DALBK, B1RBK antagonist. Here, we show that the blockage of B2RBK with HOE-140 protects mice from FSGS development, including podocyte foot process effacement and reestablishment of slit diaphragm-related proteins. However, B2RBK KO mice were not protected from FSGS. These opposite results were due to B1RBK expression. B1RBK was up regulated after ADM injection and it was exacerbated in B2RBK KO animals. Further, HOE-140 treatment down regulated B1RBK receptor. The blockade of B1RBK in B2RBK KO animals promoted FSGS regression, with a less inflammatory phenotype. These results indicate a deleterious role of both kinin receptors in FSGS model and suggest a possible crosstalk of them in disease progression.
Intake of different types of protein may be associated with differences in biomarkers among various populations. This work investigated the influence of protein intake from haem and non-haem animals as well as protein from plants on haematological and biochemical parameters in inflammation among apparently-healthy adults living in Greece, a Mediterranean country. Four hundred and ninety apparently-healthy subjects (46 +/- 16 years, 40% men), who consecutively visited Polykliniki General Hospital for routine examinations, voluntarily agreed to participate in the study (participation rate 85%). Demographic, anthropometric and lifestyle characteristics were recorded. Participants completed a valid, semi-quantitative food frequency questionnaire. Protein intake was classified into three sources: protein from haem animals, protein from non-haem animals, and protein from plant origin. Fasting blood samples were taken from all participants; uric acid, creatinine, lipids, cystatin C, haptoglobin, haemoglobin, haematocrit, iron, ferritin, white blood cells, monocytes, platelets, and C-reactive protein were measured. Protein intake from only haem animals was associated with increased haemoglobin and haematocrit levels (p < 0.05) whereas intake of protein from non-haem animals and plant origin was not associated with the investigated haematological and biochemical markers of low-grade chronic inflammation when lifestyle factors and overall dietary habits were taken into account. Intake of protein from only haem animals seems to be consistently associated with haematological markers. The confounding role of dietary habits and lifestyle variables on the tested parameters deserves further attention in future research.
Intestinal detection of nutrients is a crucial step to inform the whole body of the nutritional status. In this paradigm, peripheral information generated by nutrients is transferred to the brain, which in turn controls physiological functions, including glucose metabolism. Here, we investigated the effect of enteric glucose sensors stimulation on hypothalamic nitric oxide (NO) release in lean or in obese=diabetic (db=db) mice. By using specific NO amperometric probes implanted directly in the hypothalamus of mice, we demonstrated that NO release is stimulated in response to enteric glucose sensors activation in lean but not in db=db mice. Alteration of gut to hypothalamic NO signaling in db=db mice is associated with a drastic increase in inflammatory, oxidative=nitric oxide (iNOS, IL-1b), and endoplasmic reticulum stress (CHOP, ATF4) genes expression in the jejunum. Although we could not exclude the importance of the hypothalamic inflammatory state in obese and diabetic mice, our results provide compelling evidence that enteric glucose sensors could be considered as potential targets for metabolic diseases. Antioxid. Redox Signal. 14, 415–423.
Throughout the life span, the brain is a metabolically highly active organ that uses a large proportion of total nutrient and energy intake. Furthermore, the development and repair of neural tissue depend on the proper intake of essential structural nutrients, minerals, and vitamins. Therefore, what we eat, or refrain from eating, may have an important impact on our cognitive ability and mental performance. Two of the key areas in which diet is thought to play an important role are in optimizing neurodevelopment in children and in preventing neurodegeneration and cognitive decline during aging. From early development to aging, brain imaging can detect structural, functional, and metabolic changes in humans and modifications due to altered nutrition or to additional nutritional supplementation. Inclusion of imaging measures in clinical studies can increase understanding with regard to the modification of brain structure, metabolism, and functional endpoints and may provide early sensitive measures of long-term effects. In this symposium, the utility of existing brain imaging technologies to assess the effects of nutritional intervention in humans is described. Examples of current research showing the utility of these markers are reviewed.
Cytokine-inducible protein SSI-1 [signal transducers and activators of transcription (STAT)-induced STAT inhibitor 1, also referred to as SOCS-1 (suppressor of cytokine signaling 1) or JAB (Janus kinase-binding protein)] negatively regulates cytokine receptor signaling by inhibition of JAK kinases. The SSI family of proteins includes eight members that are structurally characterized by an SH2 domain and a C-terminal conserved region that we have called the SC-motif. In this study, we investigated the roles of these domains in the function of SSI-1. Results of reporter assays demonstrated that the pre-SH2 domain (24 aa in front of the SH2 domain) and the SH2 domain of SSI-1 were required for the suppression by SSI-1 of interleukin 6 signaling. Coexpression studies of COS7 cells revealed that these domains also were required for inhibition of three JAKs (JAK1, JAK2, and TYK2). Furthermore, deletion of the SH2 domain, but not the pre-SH2 domain, resulted in loss of association of SSI-1 with TYK2. Thus, SSI-1 associates with JAK family kinase via its SH2 domain, and the pre-SH2 domain is required for the function of SSI-1. Deletion of the SC-motif markedly reduced expression of SSI-1 protein in M1 cells, and this reduction was reversed by treatment with proteasome inhibitors, suggesting that this motif is required to protect the SSI-1 molecule from proteolytic degradation. Based on these findings, we concluded that three distinct domains of SSI-1 (the pre-SH2 domain, the SH2 domain, and the SC-motif) cooperate in the suppression of interleukin 6 signaling.
Neudesin (neuron-derived neurotrophic factor; NENF) was identified as a neurotrophic factor that is involved in neuronal differentiation and survival. It is abundantly expressed in the central nervous system, and its neurotrophic activity is exerted via the mitogen-activated protein kinase (MAPK) and phosphatidylinositol 3-kinase (PI3K) pathways. Neudesin is also an anorexigenic factor that suppresses food intake in the hypothalamus. It is a member of the membrane-associated progesterone receptor (MAPR) family and shares key structural motifs with the cytochrome b5-like heme/steroid-binding domain. Progesterone receptor membrane component 1 (PGRMC1), the first to be discovered among the MAPR family, binds progesterone to induce “rapid non-genomic effects” in biological responses that are unrelated to the nuclear progesterone receptors (PRs). Hence, neudesin may also be involved in the rapid non-genomic actions of progesterone. In this review, we summarize the identification, structure, and activity of neudesin in the central nervous system, and present an essential overview of the current understanding of its physiological roles and the prospect of elucidating its non-genomic progesterone effects.
The prevalence rates of overweight and obesity are considered an important public issue in the United States, and both of these conditions are increasing among both children and adults. There is evidence of aberrations in the vitamin D-endocrine system in obese subjects. Vitamin D deficiency is highly prevalent in patients with obesity, and many studies have demonstrated the significant effect of calcitriol on adipocytes. Genetic studies have provided an opportunity to determine which proteins link vitamin D to obesity pathology, including the vitamin D receptor, toll-like receptors, the renin-angiotensin system, apolipoprotein E, vascular endothelial growth factor, and poly (ADP-ribose) polymerase-1. Vitamin D also exerts its effect on obesity through cell-signaling mechanisms, including matrix metalloproteinases, mitogen-activated protein kinase pathways, the reduced form of nicotinamide adenine dinucleotide phosphate, prostaglandins, reactive oxygen species, and nitric oxide synthase.
In conclusion, vitamin D may have a role in obesity. The best form of vitamin D for use in the obese individuals is calcitriol because it is the active form of the vitamin D3 metabolite, its receptors are present in adipocytes, and modulates inflammatory cytokine expression.
Atherosclerosis is one of the most important contributors to the global burden of cardiovascular diseases. With the recognition of atherosclerosis as an inflammatory disease, nutrition research interest has expanded towards the role of dietary patterns in the prevention of atherosclerosis primarily focused on associations with early inflammatory markers. This review summarizes the latest evidence from January 2010 until January 2013 of eight observational studies on the associations between empirically-derived dietary patterns and diet quality scores with markers of inflammation and endothelial function. Overall, results of recently published cohort studies support those of previously published cross-sectional studies suggesting that consuming a healthy type of diet characteristically abundant in fruits and vegetables is associated with lower concentrations of C-reactive protein and other inflammatory markers. Unfavourable associations were found between eating a Western dietary pattern high in meat and inflammatory markers. Different statistical approaches of deriving dietary patterns were applied in these studies and most of them lacked in reporting absolute intakes of foods and/or food groups. Future prospective cohort studies are needed to evaluate long-term associations between dietary patterns and changes in inflammatory markers by comparing various approaches of dietary pattern derivation within a population. Reporting absolute intakes of foods and/or food groups may also facilitate the identification of a typical dietary pattern that may beneficially influence inflammation.
Magnesium is the fourth most abundant mineral and the second most abundant intracellular divalent cation and has been recognized as a cofactor for >300 metabolic reactions in the body. Some of the processes in which magnesium is a cofactor include, but are not limited to, protein synthesis, cellular energy production and storage, reproduction, DNA and RNA synthesis, and stabilizing mitochondrial membranes. Magnesium also plays a critical role in nerve transmission, cardiac excitability, neuromuscular conduction, muscular contraction, vasomotor tone, blood pressure, and glucose and insulin metabolism. Because of magnesium's many functions within the body, it plays a major role in disease prevention and overall health. Low levels of magnesium have been associated with a number of chronic diseases including migraine headaches, Alzheimer's disease, cerebrovascular accident (stroke), hypertension, cardiovascular disease, and type 2 diabetes mellitus. Good food sources of magnesium include unrefined (whole) grains, spinach, nuts, legumes, and white potatoes (tubers). This review presents recent research in the areas of magnesium and chronic disease, with the goal of emphasizing magnesium's role in disease prevention and overall health.
Vegetables are universally promoted as healthy. Dietary Guidelines for Americans 2010 recommend that you make half of your plate fruits and vegetables. Vegetables are diverse plants that vary greatly in energy content and nutrients. Vegetables supply carbohydrates, dietary fiber, and resistant starch in the diet, all of which have been linked to positive health outcomes. Fiber lowers the incidence of cardiovascular disease and obesity. In this paper, the important role of white vegetables in the human diet is described, with a focus on the dietary fiber and resistant starch content of white vegetables. Misguided efforts to reduce consumption of white vegetables will lower intakes of dietary fiber and resistant starch, nutrients already in short supply in our diets.
Insulin resistance (IR) links Alzheimer's disease (AD) with oxidative damage, cholinergic deficit, and cognitive impairment. Peroxisome proliferator-activated receptor γ (PPARγ) agonist pioglitazone previously used to treat type 2 diabetes mellitus (T2DM) has also been demonstrated to be effective in anti-inflammatory reaction and anti-oxidative stress in the animal models of AD and other neuroinflammatory diseases. Here, we investigated the effect of pioglitazone on learning and memory impairment and the molecular events that may cause it in fructose-drinking insulin resistance rats. We found that long-term fructose-drinking causes insulin resistance, oxidative stress, down-regulated activity of cholinergic system, and cognitive deficit, which could be ameliorated by pioglitazone administration. The results from the present study provide experimental evidence for using pioglitazone in the treatment of brain damage caused by insulin resistance.
OBJECTIVES
Diabetes is associated with oxidative stress and increased mortality, but a possible correlation between leukocyte-endothelium interactions, oxidative stress, and silent myocardial ischemia (SMI) is yet to be confirmed.RESEARCH DESIGN AND METHODS
Mitochondrial dysfunction and interactions between leukocytes and human umbilical vein endothelial cells were evaluated in 200 type 2 diabetic patients (25 with SMI) and 60 body composition- and aged-matched control subjects. A possible correlation between these parameters and the onset of SMI was explored, and anthropometric and metabolic parameters were also analyzed.RESULTSWaist, levels of triglycerides, proinflammatory cytokines (interleukin-6 and tumor necrosis factor-α), HbA(1c), high-sensitivity C-reactive protein (hs-CRP), glucose, and insulin, and homeostasis model assessment of insulin resistance were higher in diabetic patients than in control subjects. However, no statistical differences in hs-CRP and insulin levels were detected when the data were adjusted for waist. None of these parameters varied between SMI and non-SMI patients. Mitochondrial function was impaired and leukocyte-endothelium interactions were more frequent among diabetic patients, which was evident in the lower mitochondrial O(2) consumption, membrane potential, polymorphonuclear cell rolling velocity, and GSH/GSSG ratio, and in the higher mitochondrial reactive oxygen species production and rolling flux, adhesion, and vascular cell adhesion molecule-1 (VCAM-1) and E-selectin molecules observed in these subjects. Moreover, these differences correlated with SMI. Statistical differences were maintained after adjusting the data for BMI and waist, with the exception of VCAM-1 levels when adjusted for waist.CONCLUSIONS
Oxidative stress, mitochondrial dysfunction, and endothelium-inducing leukocyte-endothelium interactions are features of type 2 diabetes and correlate with SMI.
Colorectal cancer represents the most common malignancy of the gastrointestinal tract. Owing to differences in dietary habits and lifestyle, this neoplasm is more common in industrialized countries than in developing ones. Evidence from a wide range of sources supports the assumption that the link between diet and colorectal cancer may be due to an imbalance of the intestinal microflora.
Probiotic bacteria are live microorganisms that, when administered in adequate amounts, confer a healthy benefit on the host, and they have been investigated for their protective anti-tumor effects. In vivo and molecular studies have displayed encouraging findings that support a role of probiotics in colorectal cancer prevention.
Several mechanisms could explain the preventive action of probiotics against colorectal cancer onset. They include: alteration of the intestinal microflora; inactivation of cancerogenic compounds; competition with putrefactive and pathogenic microbiota; improvement of the host's immune response; anti-proliferative effects via regulation of apoptosis and cell differentiation; fermentation of undigested food; inhibition of tyrosine kinase signaling pathways.
The mechanisms of regulation, activation and signal transduction of the angiotensin II (Ang II) type 1 (AT1) receptor have been studied extensively in the decade after its cloning. The AT1 receptor is a major component of the renin-angiotensin system (RAS). It mediates the classical biological actions of Ang II. Among the structures required for regulation and activation of the receptor, its carboxyl-terminal region plays crucial roles in receptor internalization, desensitization and phosphorylation. The mechanisms involved in heterotrimeric G-protein coupling to the receptor, activation of the downstream signaling pathway by G proteins and the Ang II signal transduction pathways leading to specific cellular responses are discussed. In addition, recent work on the identification and characterization of novel proteins associated with carboxyl-terminus of the AT1 receptor is presented. These novel proteins will advance our understanding of how the receptor is internalized and recycled as they provide molecular mechanisms for the activation and regulation of G-protein-coupled receptors.Keywords: RAS, Ang II, receptor, internalization, recycling, yeast two-hybrid system
Excessive dietary fructose intake may have an important role in the current epidemics of fatty liver, obesity and diabetes as its intake parallels the development of these syndromes and because it can induce features of metabolic syndrome. The effects of fructose to induce fatty liver, hypertriglyceridemia and insulin resistance, however, vary dramatically among individuals. The first step in fructose metabolism is mediated by fructokinase (KHK), which phosphorylates fructose to fructose-1-phosphate; intracellular uric acid is also generated as a consequence of the transient ATP depletion that occurs during this reaction. Here we show in human hepatocytes that uric acid up-regulates KHK expression thus leading to the amplification of the lipogenic effects of fructose. Inhibition of uric acid production markedly blocked fructose-induced triglyceride accumulation in hepatocytes in vitro and in vivo. The mechanism whereby uric acid stimulates KHK expression involves the activation of the transcription factor ChREBP, which, in turn, results in the transcriptional activation of KHK by binding to a specific sequence within its promoter. Since subjects sensitive to fructose often develop phenotypes associated with hyperuricemia, uric acid may be an underlying factor in sensitizing hepatocytes to fructose metabolism during the development of fatty liver.
Dietary factors play an important role in glycemic control in diabetic patients. However, little is known about their effects among Chinese diabetic patients, whose diets are typically abundant in fiber and high in glycemic index (GI) values.
934 patients with type 2 diabetes and 918 healthy volunteers from Pudong New Area, Shanghai, China, were interviewed during the period of Oct-Dec, 2006 to elicit demographic characteristics and lifestyle factors. Dietary habits were assessed using a validated food frequency questionnaire. Anthropometric measurements, bio-specimen collection and biochemical assays were conducted at the interview according to a standard protocol. In this population, diabetic patients consumed lower levels of energy and macronutrients but had higher levels of fasting plasma glucose (FPG), glycolated hemoglobin A1c (HbA1c), triglyceride and body mass index than healthy adults. While the average consumption levels of the nutrients among diabetic patients did not vary along duration of the disease, the average levels of FPG and HbA1c increased with increasing duration. Regardless of diabetes duration, HbA1c level was observed lower in patients having a higher fiber or lower GI intake. Compared with those with the lowest tertile intake of fiber, the adjusted odds ratios (ORs) for poor glycemic control reduced from 0.75 (95%CI: 0.54-1.06) to 0.51 (95%CI: 0.34-0.75) with increasing tertile intake (P for trend <0.001).
Dietary fiber may play an important role in reducing HbA1c level. Increasing fiber intake may be an effective approach to improve glycemic control among Chinese diabetic patients.
It is increasingly recognized that certain fundamental changes in diet and lifestyle that occurred after the Neolithic Revolution, and especially after the Industrial Revolution and the Modern Age, are too recent, on an evolutionary time scale, for the human genome to have completely adapted. This mismatch between our ancient physiology and the western diet and lifestyle underlies many so-called diseases of civilization, including coronary heart disease, obesity, hypertension, type 2 diabetes, epithelial cell cancers, autoimmune disease, and osteopo-rosis, which are rare or virtually absent in hunter–gatherers and other non-westernized popula-tions. It is therefore proposed that the adoption of diet and lifestyle that mimic the beneficial characteristics of the preagricultural environment is an effective strategy to reduce the risk of chronic degenerative diseases.
Obesity and type 2 diabetes are associated with chronically elevated systemic levels of IL-6, a pro-inflammatory cytokine with a role in skeletal muscle metabolism that signals through the IL-6 receptor (IL-6Rα). We hypothesized that skeletal muscle in obesity-associated type 2 diabetes develops a resistance to IL-6. By utilizing western blot analysis, we demonstrate that IL-6Rα protein was down regulated in skeletal muscle biopsies from obese persons with and without type 2 diabetes. To further investigate the status of IL-6 signaling in skeletal muscle in obesity-associated type 2 diabetes, we isolated satellite cells from skeletal muscle of people that were healthy (He), obese (Ob) or were obese and had type 2 diabetes (DM), and differentiated them in vitro into myocytes. Down-regulation of IL-6Rα was conserved in Ob myocytes. In addition, acute IL-6 administration for 30, 60 and 120 minutes, resulted in a down-regulation of IL-6Rα protein in Ob myocytes compared to both He myocytes (P<0.05) and DM myocytes (P<0.05). Interestingly, there was a strong time-dependent regulation of IL-6Rα protein in response to IL-6 (P<0.001) in He myocytes, not present in the other groups. Assessing downstream signaling, DM, but not Ob myocytes demonstrated a trend towards an increased protein phosphorylation of STAT3 in DM myocytes (P = 0.067) accompanied by a reduced SOCS3 protein induction (P<0.05), in response to IL-6 administration. Despite this loss of negative control, IL-6 failed to increase AMPKα2 activity and IL-6 mRNA expression in DM myocytes. There was no difference in fusion capacity of myocytes between cell groups. Our data suggest that negative control of IL-6 signaling is increased in myocytes in obesity, whereas a dysfunctional IL-6 signaling is established further downstream of IL-6Rα in DM myocytes, possibly representing a novel mechanism by which skeletal muscle function is compromised in type 2 diabetes.
The body's physiological stability is maintained by the influence of the autonomic nervous system upon the dynamic interaction of multiple systems. These physiological systems, their nature and structure, and the factors which influence their function have been poorly defined. A greater understanding of such physiological systems leads to an understanding of the synchronised function of organs in each neural network i.e. there is a fundamental relationship involving sensory input and/or sense perception, neural function and neural networks, and cellular and molecular biology. Such an approach compares with the bottom-up systems biology approach in which there may be an almost infinite degree of biochemical complexity to be taken into account.
The purpose of this article is to discuss a novel cognitive, top-down, mathematical model of the physiological systems, in particular its application to the neuroregulation of blood pressure.
This article highlights the influence of sensori-visual input upon the function of the autonomic nervous system and the coherent function of the various organ networks i.e. the relationship which exists between visual perception and pathology.
The application of Grakov's model may lead to a greater understanding of the fundamental role played by light e.g. regulating acidity, levels of Magnesium, activation of enzymes, and the various factors which contribute to the regulation of blood pressure. It indicates that the body's regulation of blood pressure does not reside in any one neural or visceral component but instead is a measure of the brain's best efforts to maintain its physiological stability.
In 288 men and women from general population in a cross-sectional survey, all neuropsychological tests were negatively associated with age; memory and executive function were also positively related with education. The hypertensives (HT) were less efficient than the normotensives (NT) in the test of memory with interference at 10 sec (MI-10) (-33%, P = 0.03), clock drawing test (CLOX) (-28%, P < 0.01), and mini-mental state examination (MMSE) (-6%, P = 0.02). Lower MMSE, MI-10, and CLOX were predicted by higher systolic (odds ratio, OR, 0.97, P = 0.02; OR 0.98, P < 0.005; OR 0.95, P < 0.001) and higher pulse blood pressure (BP) (OR 0.97, P = 0.02; OR 0.97, P < 0.01; and 0.95, P < 0.0001). The cognitive reserve index (CRI) was 6% lower in the HT (P = 0.03) and was predicted by higher pulse BP (OR 0.82, P < 0.001). The BP vectors of lower MMSE, MI-10, and CLOX were directed towards higher values of systolic and diastolic BP, that of low CRI towards higher systolic and lower diastolic. The label of hypertension and higher values of systolic or pulse BP are associated to worse memory and executive functions. Higher diastolic BP, although insufficient to impair cognition, strengthens this association. CRI is predicted by higher systolic BP associated to lower diastolic BP.
Excess intake of dietary salt is estimated to be one of the leading risks to health worldwide. Major national and international health organizations, along with many governments around the world, have called for reductions in the consumption of dietary salt. This paper discusses behavioural and population interventions as mechanisms to reduce dietary salt. In developed countries, salt added during food processing is the dominant source of salt and largely outside of the direct control of individuals. Population-based interventions have the potential to improve health and to be cost saving for these countries. In developing economies, where salt added in cooking and at the table is the dominant source, interventions based on education and behaviour change have been estimated to be highly cost effective. Regardless, countries with either developed or developing economies can benefit from the integration of both population and behavioural change interventions.
Osteoporosis is the index disease for calcium deficiency, just as rickets/osteomalacia is the index disease for vitamin D deficiency, but there is considerable overlap between them. The common explanation for this overlap is that hypovitaminosis D causes malabsorption of calcium which then causes secondary hyperparathyroidism and is effectively the same thing as calcium deficiency. This paradigm is incorrect. Hypovitaminosis D causes secondary hyperparathyroidism at serum calcidiol levels lower than 60 nmol/L long before it causes malabsorption of calcium because serum calcitriol (which controls calcium absorption) is maintained until serum calcidiol falls below 20 nmol/L. This secondary hyperparathyroidism, probably due to loss of a "calcaemic" action of vitamin D on bone first described in 1957, destroys bone and explains why vitamin D insufficiency is a risk factor for osteoporosis. Vitamin D thus plays a central role in the maintenance of the serum (ionised) calcium, which is more important to the organism than the preservation of the skeleton. Bone is sacrificed when absorbed dietary calcium does not match excretion through the skin, kidneys and bowel which is why calcium deficiency causes osteoporosis in experimental animals and, by implication, in humans.
It is general knowledge that glucose homeostasis possesses very limited buffering capacities, while energy homeostasis in its fat-controlling part enjoys practically unlimited energy stores. Logically, a control system with a limited buffer should thoroughly defend the “consumption” part. Indeed, existing experimental data (briefly reviewed here) show important properties of the CHO intake control that is different from or not shown for the fat intake control.
Dietary proteins influence body weight by affecting four targets for body weight regulation: satiety, thermogenesis, energy efficiency, and body composition. Protein ingestion results in higher ratings of satiety than equicaloric amounts of carbohydrates or fat. Their effect on satiety is mainly due to oxidation of amino acids fed in excess; this effect is higher with ingestion of specific "incomplete" proteins (vegetal) than with animal proteins. Diet-induced thermogenesis is higher for proteins than for other macronutrients. The increase in energy expenditure is caused by protein and urea synthesis and by gluconeogenesis. This effect is higher with animal proteins containing larger amounts of essential amino acids than with vegetable proteins. Specifically, diet-induced thermogenesis increases after protein ingestion by 20 - 30 %, but by only 5 - 10 % after carbohydrates and 0 - 5 % after ingestion of fat. Consumption of higher amounts of protein during dietary treatment of obesity resulted in greater weight loss than with lower amounts of protein in dietary studies lasting up to one year. During weight loss and decreased caloric intake, a relatively increased protein content of the diet maintained fat-free mass (i. e. muscle mass) and increased calcium balance, resulting in preservation of bone mineral content. This is of particular importance during weight loss after bariatric surgery because these patients are at risk for protein malnutrition. Adequate dietary protein intake in diabetes type 2 is of specific importance since proteins are relatively neutral with regard to glucose and lipid metabolism, and they preserve muscle and bone mass, which may be decreased in subjects with poorly controlled diabetes. Ingestion of dietary proteins in diabetes type 1 exerts a delayed postprandial increase in blood glucose levels due to protein-induced stimulation of pancreatic glucagon secretion. Higher than minimal amounts of protein in the diet needed for nitrogen balance may play an important role for the increasing number of elderly obese subjects in our industrialized societies, since proteins exert beneficial effects in the conditions of overweight, metabolic syndrome, cardiovascular risk factors, bone health, and sarcopenia. Adverse effects of increased dietary proteins have been observed in subjects with renal impairment- this problem is frequently observed in the elderly, hypertensive, and diabetic population. Nevertheless, dietary proteins deserve more attention than they have received in the past.
The kallikrein-kinin system (KKS) constitutes a complex multienzyme cascade that produces several bioactive kinin peptides and their derivatives including bradykinin. In addition to the classical notion of the KKS as a potent vasodilator and a mediator of inflammatory responses, recent studies suggest a link between the KKS and oxidative stress. A number of established mouse models with altered levels of KKS components opened the way to evaluate precise functions of the KKS. Here we review recent findings on the role of the KKS in cardiovascular diseases and chronic kidney diseases, and discuss potential benefits of KKS activation in these diseases.
Deletion of both B1R and B2R in a diabetic mouse model exacerbates its renal phenotypes, suggesting that the KKS exerts protective effects on diabetic nephropathy by suppressing oxidative stress, presumably via nitric oxide and prostaglandins.
Accumulating evidence has highlighted the importance of the KKS as a protective system against oxidative stress and organ damage in the heart and kidney. The activation of the KKS by angiotensin I-converting enzyme inhibitors and vasopeptidase inhibitors is likely to be beneficial in senescence-associated cardiovascular diseases and chronic kidney diseases.
Hypertension, diabetes, obesity, and dyslipidemia are risk factors that characterize metabolic syndrome (MetS), which increases the risk for stroke by 40%. In a preliminary study, our aim was to evaluate cerebrovascular reactivity and oxygen metabolism in subjects free of vascular disease but with one or more of these risk factors. Volunteers (n=15) 59±15 (mean±SD)years of age clear of cerebrovascular disease by magnetic resonance angiography but with one or more risk factors were studied by quantitative positron emission tomography for measure ment of cerebral blood flow, oxygen consumption, oxygen extraction fraction (OEF), and acetazolamide cerebrovascular reactivity. Eight of ten subjects with MetS risk factors had OEF >50%. None of the five without risk factors had OEF >50%. The presence of MetS risk factors was highly correlated with OEF >50% by Fisher's exact test (p<0.007). The increase in OEF was significantly (P<0.001) correlated with cerebral metabolic rate for oxygen. Increased OEF was not associated with compromised acetazolamide cerebrovascular reactivity. Subjects with one or more MetS risk factors are characterized by increased cerebral oxygen consumption and ischemic stress, which may be related to increased risk of cerebrovascular disease and stroke.
Increasing evidence suggests that diets high in polyunsaturated fatty acids (PUFA) confer health benefits by improving insulin sensitivity and lipid metabolism in liver, muscle and adipose tissue.
The present study investigates metabolic responses in two different lines of mice either selected for high body weight (DU6) leading to rapid obesity development, or selected for high treadmill performance (DUhTP) leading to a lean phenotype. At 29 days of age the mice were fed standard chow (7.2% fat, 25.7% protein), or a high-fat diet rich in n-3 PUFA (n-3 HFD, 27.7% fat, 19% protein) or a high-fat diet rich in n-6 PUFA (n-6 HFD, 27.7% fat, 18.6% protein) for 8 weeks. The aim of the study was to determine the effect of these PUFA-rich high-fat diets on the fatty acid profile and on the protein expression of key components of insulin signalling pathways.
Plasma concentrations of leptin and insulin were higher in DU6 in comparison with DUhTP mice. The high-fat diets stimulated a strong increase in leptin levels and body fat only in DU6 mice. Muscle and liver fatty acid composition were clearly changed by dietary lipid composition. In both lines of mice n-3 HFD feeding significantly reduced the hepatic insulin receptor β protein concentration which may explain decreased insulin action in liver. In contrast, protein kinase C ζ expression increased strongly in abdominal fat of n-3 HFD fed DUhTP mice, indicating enhanced insulin sensitivity in adipose tissue.
A diet high in n-3 PUFA may facilitate a shift from fuel deposition in liver to fuel storage as fat in adipose tissue in mice. Tissue specific changes in insulin sensitivity may describe, at least in part, the health improving properties of dietary n-3 PUFA. However, important genotype-diet interactions may explain why such diets have little effect in some population groups.
The phenomenon of selective neuronal vulnerability to neurological diseases or insults, such as ischemia-reperfusion, brain trauma, and ageing-associated neurodegeneration, was described in the hippocampus nearly a century ago. The hippocampus has been the focus for many of the studies designed to identify the stresses to which neurons respond differentially, as well as the molecular, cellular and physiological mechanisms that may be responsible for such differential response patterns. Although final conclusions have not yet been reached on the mechanisms for differential neuronal responses to stress and disease, genomic and proteomic analyses, in conjunction with biochemical and physiological measurements, are beginning to point to endogenous differences between vulnerable and resistant populations of neurons. Collectively, these studies have identified differential patterns of energy metabolism, generation of reactive oxygen species, handling of transient intracellular calcium elevations, and the activity of the neurotransmitter glutamate, as some of the key processes that lead to selective sensitivity to neurological stresses. The genomic and proteomic analyses have revealed that differences in gene expression related to inflammatory and immune responses and responses to oxidative stress represent endogenous processes differentially expressed in neurons selectively vulnerable to stresses. The same is true for genes involved in DNA, RNA, and protein repair. Cells that are more resistant to stresses and disease conditions express genes for energy generation, nervous system development, and synaptic transmission at higher levels than those found in vulnerable neurons. The molecular pathways identified above and described in this chapter may eventually determine the targets for future therapeutic interventions for neurodegenerative diseases.
Despite 30 plus years of intensive research, gaps remain in our understanding of Alzheimer disease (AD) pathogenesis and approaches to treatment. However, the recent rapid shift to a paradigm that focuses on the roles of metabolic dysfunction and insulin and insulin-like growth factor (IGF) resistance as causal agents of cognitive impairment and neurodegeneration holds promise. The overarching hypothesis, that AD is a brain diabetes, accounts for the impairments in neuronal survival, myelin maintenance, energy metabolism, synaptic integrity, and plasticity, and the neuropathological processes. This chapter discusses the roles of aging, lifestyle choices, peripheral insulin resistance diseases, including obesity, type 2 diabetes mellitus, nitrosamine exposures, and familial/genetic factors as mediators of brain diabetes, cognitive impairment, and neurodegeneration. It proposes that progressive cognitive impairment and neurodegeneration in AD are effectuated by a positive feedback mal-signaling cascade, whereby declining function of insulin/IGF networks dysregulate lipid metabolism and increase local levels of toxic ceramides.
Longevity is a very complex phenomenon, because many environmental, behavioral, socio-demographic and dietary factors influence the physiological pathways of aging and life-expectancy. Nutrition has been recognized to have an important impact on overall mortality and morbidity; and its role in extending life expectancy has been the object of extensive scientific research. This paper reviews the pathophysiological mechanisms that potentially link aging with diet and the scientific evidence supporting the anti-aging effect of the traditional Mediterranean diet, as well as of some specific foods. The diet and several of its components have additionally been shown to have beneficial effects on the co-morbidities typical of elderly populations. Furthermore, the epigenetic effects of diet on the aging process - through calorie restriction and the consumption of foods like red wine, orange juice, probiotics and prebiotics - have attracted scientific interest. Some, such as dark chocolate, red wine, nuts, beans, avocados are being promoted as anti-aging foods, due to their anti-oxidative and anti-inflammatory properties. Finally, an important moderator in the relationship between diet, longevity and human health remains the socio-economic status of individual, as a healthy diet, due to its higher cost, is closely related to higher financial and educational status.
Objective:
Agitation and depression are among the commonest behavioural and psychological symptoms exhibited by Alzheimer's disease patients. However, their pathophysiology remains unclear. We therefore investigated the relationship between the brain metabolism in the posterior cingulate gyrus and the dorsolateral prefrontal cortex, and agitation and depression in patients diagnosed with Alzheimer's disease.
Methods:
We recruited 26 patients (14 women and 12 men) with a mean age of 75 years and probable Alzheimer's disease. All patients completed the Mini-Mental State Examination (MMSE), the Geriatric Depression Scale-Short Form (GDS) assessment, and the Cohen-Mansfield Agitation Inventory (CMAI) in order to evaluate cognition, depression, and agitation, respectively. All subjects underwent magnetic resonance imaging and (1)H-magnetic resonance spectroscopy of the brain. The ratios of N-acetylaspartate (NAA), choline (Cho), and myo-inositol (mI) to creatine (Cr) in the posterior cingulate gyrus and the dorsolateral prefrontal cortex were measured and compared with neuropsychological test results.
Results:
The MMSE scores correlated positively with the NAA/Cr ratio in the left posterior cingulate gyrus (r = 0.56; p = 0.001). The CMAI scores correlated negatively with the NAA/Cr ratio in the left posterior cingulate gyrus (r = -0.46; p = 0.02). The GDS scores correlated positively with the Cho/Cr ratio in the left dorsolateral prefrontal cortex (r = 0.59; p = 0.01), and mI/Cr in both left (r = 0.47; p = 0.03) and right (r = 0.47; p = 0.03) cingulate gyri.
Conclusions:
Agitation and depression levels correlated with different neurochemical metabolites in specific brain areas. We conclude that various neuropsychiatric symptoms might have separate pathophysiologies.
Recent studies have suggested that depression might be an aggravating factor in Alzheimer's disease (AD). The aim of study was to compare depressive symptoms and gray matter volume between AD patients with comorbid depression and patients with dementia only. 49 patients with AD, 57 with mild cognitive impairment (MCI), and 50 healthy control subjects were assessed using the Consortium to Establish a Registry for Alzheimer's disease(K-CERAD) and the Geriatric Depression Scale(GDS). All magnetic resonance imaging (MRI)s were analyzed using Voxel-based morphometry (VBM). Seventeen AD patients with depression versus 32 patients with dementia only showed decreased immediate recall for a word list (8.7±1.1 vs. 10.1±1.5, z=3.6, p<0.01) and constructional praxis scores (3.7±0.9 vs. 5.3±2.1, z=2.5, p=0.01). Compared to 32 patients with dementia, seventeen AD patients with depression showed decreased gray matter volume in the left inferior temporal gyrus (-56, -19, -31; КE=578, t=3.80, puncorr<0.001). The MCI group showed decreased gray matter volume in the right hippocampal gyrus compared to healthy control group. Our results suggest that depressive symptoms may be associated with the volume changes of frontal and temporal lobe in patients with AD.
To determine whether high blood pressure (BP) levels are associated with faster decline in specific cognitive domains.
Prospective longitudinal cohort.
Uniform Data Set of the National Institutes of Health, National Institute on Aging Alzheimer's Disease Centers.
One thousand three hundred eighty-five participants with a diagnosis of mild cognitive impairment (MCI) and measured BP values at baseline and two annual follow-up visits.
Neuropsychological test scores and Clinical Dementia Rating Sum of Boxes (CDR Sum) score.
Participants with MCI with two or three annual occasions of high BP values (systolic BP ≥140 mmHg or diastolic BP ≥90 mmHg) had significantly faster decline on neuropsychological measures of visuomotor sequencing, set shifting, and naming than those who were normotensive on all three occasions. High systolic BP values were associated as well with faster decline on the CDR Sum score.
Hypertension is associated with faster cognitive decline in persons at risk for dementia.
Stability of pure stevioside and rebaudioside A in carbonated phosphoric and citric acidified beverages during long-term storage was observed chemically, microbiologically, and organoleptically. Thin-layer chromatography and high-pressure liquid chromatography were used to follow the chemical degradation of these Stevia sweeteners. Some degradation of both sweeteners was observed after 2 months of storage at 37 °C; however, there were no significant changes at room temperature or below following 5 months of storage of stevioside, or 3 months of storage of rebaudioside A. Exposure to 1 week of sunlight did not affect stevioside but resulted in approximately 20% loss of rebaudioside A. Heating at 60 °C for 6 days resulted in 0-6% loss of the sweeteners.
Introduction
Physiological mechanisms of satiation and satiety
Measuring satiation and satiety
The effects of foods and drinks on satiety
The effect of external factors on satiation and satiety
Satiation, satiety and weight control
Conclusions
Summary
In the context of the rising prevalence of obesity around the world, it is vital to understand how energy balance and bodyweight are controlled. The ability to balance energy intake and expenditure is critical to survival, and sophisticated physiological mechanisms have developed in order to do this, including the control of appetite. Satiation and satiety are part of the body's appetite control system and are involved in limiting energy intake. Satiation is the process that causes one to stop eating; satiety is the feeling of fullness that persists after eating, suppressing further consumption, and both are important in determining total energy intake.
Satiation and satiety are controlled by a cascade of factors that begin when a food or drink is consumed and continues as it enters the gastrointestinal tract and is digested and absorbed. Signals about the ingestion of energy feed into specific areas of the brain that are involved in the regulation of energy intake, in response to the sensory and cognitive perceptions of the food or drink consumed, and distension of the stomach. These signals are integrated by the brain, and satiation is stimulated. When nutrients reach the intestine and are absorbed, a number of hormonal signals that are again integrated in the brain to induce satiety are released. In addition to these episodic signals, satiety is also affected by fluctuations in hormones, such as leptin and insulin, which indicate the level of fat storage in the body.
Satiation and satiety can be measured directly via food intake or indirectly via ratings of subjective sensations of appetite. The most common study design when measuring satiation or satiety over a short period is using a test preload in which the variables of interest are carefully controlled. This is followed by subjects rating aspects of their appetite sensations, such as fullness or hunger, at intervals and then, after a predetermined time interval, a test meal at which energy intake is measured. Longer‐term studies may provide foods or drinks of known composition to be consumed ad libitum and use measures of energy intake and/or appetite ratings as indicators of satiety. The measurement of satiation and satiety is complicated by the fact that many factors besides these internal signals may influence appetite and energy intake, for example, physical factors such as bodyweight, age or gender, or behavioural factors such as diet or the influence of other people present. For this reason, the majority of studies on satiation and satiety take place in a laboratory, where confounders can be controlled as much as possible, and are, therefore, of short duration.
It is possible for any food or drink to affect appetite, and so it is important to determine whether, for a given amount of energy, particular variables have the potential to enhance or reduce satiation or satiety. A great deal of research has been conducted to investigate the effect of different foods, drinks, food components and nutrients on satiety. Overall, the characteristic of a food or drink that appears to have the most impact on satiety is its energy density. That is the amount of energy it contains per unit weight (kJ/g, kcal/g). When energy density is controlled, the macronutrient composition of foods does not appear to have a major impact on satiety. In practice, high‐fat foods tend to have a higher energy density than high‐protein or high‐carbohydrate foods, and foods with the highest water content tend to have the lowest energy density. Some studies have shown that energy from protein is more satiating than energy from carbohydrate or fat. In addition, certain types of fibre have been shown to enhance satiation and satiety. It has been suggested that energy from liquids is less satiating then energy from solids. However, evidence for this is inconsistent, and it may be the mode of consumption ( i.e. whether the liquid is perceived to be a food or drink) that influences its effect on satiety. Alcohol appears to stimulate energy intake in the short‐term, and consuming energy from alcohol does not appear to lead to a subsequent compensatory reduction in energy intake.
The consumption of food and drink to provide energy is a voluntary behaviour, and, despite the existence of sophisticated physiological mechanisms to match intake to requirements, humans often eat when sated and sometimes refrain from eating when hungry. Thus, there are numerous influences on eating behaviour beyond satiation and satiety. These include: the portion size, appeal, palatability and variety of foods and drinks available; the physiological impact on the body of physical activity and sleep; and other external influences such as television viewing and the effect of social situations.
Because satiation and satiety are key to controlling energy intake, inter‐individual differences in the strength of these signals and responsiveness to their effects could affect risk of obesity. Such differences have been observed at a genetic, physiological and behavioural level and may be important to consider in strategies to prevent or treat obesity.
Overall, it is clear that, although the processes of satiation and satiety have the potential to control energy intake, many individuals override the signals generated. Hence, in such people, satiation and satiety alone are not sufficient to prevent weight gain in the current obesogenic environment. Knowledge about foods, ingredients and dietary patterns that can enhance satiation and satiety is potentially useful for controlling bodyweight. However, this must be coupled with an understanding of the myriad of other factors that influence eating behaviour, in order to help people to control their energy intake.
Despite intensive investigation, a clear understanding of the metabolic disturbances in diabetes mellitus and their temporal relationship to each other during disease development has still not emerged. With emphasis on non-insulin-dependent diabetes (NIDDM), three possibilities are explored here: (1) that the insulin resistance characteristic of obesity/NIDDM syndromes is the result rather than the cause of hyperinsulinemia, as is widely held, (2) that the linkage between hyperactivity of the pancreatic β-cell and peripheral insulin resistance is vested in excessive delivery of lipid substrate from liver to the muscle bed, and (3) that conceivably hyperamylinemia works in concert with hyperinsulinemia in promoting overproduction of very-low-density lipoproteins by the liver, and thus in the etiology of muscle insulin resistance. © 1994 Wiley-Liss, Inc.
Recent studies indicate that aldosterone/mineralocorticoid receptor (MR) is a major contributor of chronic kidney disease (CKD) progression. Aldosterone/MR induces glomerular podocyte injury, causing the disruption of the glomerular filtration barrier and proteinuria. Conversely, MR antagonists substantially reduce proteinuria, which can be partly attributable to the protective effects on podocytes. Aldosterone excess, caused by adipocyte-derived aldosterone-releasing factors and other mechanisms, can be pathologically important in the renal complication of metabolic syndrome. A rat model of metabolic syndrome exhibits podocyte injury and proteinuria with serum aldosterone elevation, and the renal damage is prevented by MR blockade. Accumulating data also indicate that MR inhibition can confer renoprotection in a subgroup with low or normal aldosterone levels. We have recently identified the cross-talk between MR and small GTPase Rac1, providing one theoretical basis for the renoprotective effects of MR antagonists in non-high-aldosterone subjects. MR blockade can be a promising strategy for preventing CKD progression, and future clinical trials will conclusively determine the efficacy and tolerability of selective MR inhibition in CKD and metabolic syndrome.