Lipids in Health and Disease

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Selection process of the participants
Incidence density of IS according to lipids and lipid ratios by tertile category
HRs† and 95% CIs of IS by tertile category of lipid variables according to sex. †Adjusted variables: age, retirement status, education level, BMI, alcohol consumption, smoking index, physical activities, hypertension, diabetes, CKD, and HUA. For TG/HDL-C, TC and LDL-C were additionally adjusted. For LDL-C/HDL-C, TG was additionally adjusted
RCS analysis of the relationship between the four nontraditional blood lipid levels and IS (A–D). Adjusted variables: age, sex, retirement status, education level, BMI, alcohol consumption, smoking index, physical activities, hypertension, diabetes, CKD, and HUA. For TG/HDL-C, TC and LDL-C were additionally adjusted. For LDL-C/HDL-C, TG was additionally adjusted
  • Minhua TangMinhua Tang
  • Qi ZhaoQi Zhao
  • Kangqi YiKangqi Yi
  • [...]
  • Yonggen JiangYonggen Jiang
Background The correlation between nontraditional lipids and ischemic stroke (IS) is inconsistent and controversial. This study aimed to examine the association of four nontraditional lipids with IS risk in Chinese adults. Methods This prospective community-based cohort study was performed in Songjiang District, Shanghai, China. The study began in 2016 and included 34,294 participants without stroke before the investigation. The association between nontraditional lipids (nonhigh-density lipoprotein cholesterol [non-HDL-C], total cholesterol/high-density lipoprotein cholesterol [TC/HDL-C], triglyceride [TG]/HDL-C, and low-density lipoprotein cholesterol [LDL-C]/HDL-C) and IS was studied with multivariate Cox regression models. The dose–response associations between these four serum lipids and IS were explored using restricted cubic spline (RCS) analysis. Results There were a total of 458 IS cases with 166,380 person-years of follow-up. Compared with the lowest tertiles, the highest tertiles of the nontraditional blood lipids showed greater IS risk after controlling for potential confounders. The hazard ratios (HRs) and 95% confidence intervals (95% CIs) were as follows: TC/HDL-C, 1.63 (1.28–2.07); TG/HDL-C, 1.65 (1.28–2.13); LDL-C/HDL-C, 1.51 (1.18–1.92); and non-HDL-C, 1.43 (1.13–1.81). The fully adjusted RCS curves presented a nonlinear relationship, and the risk increased when the TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C levels were > 3.47, > 0.92, and > 1.98, respectively. Conclusions This community-based cohort study presents a positive association between the four nontraditional lipids and IS incidence. Maintaining relatively low lipid ratios can be beneficial for preventing stroke. Nontraditional lipids can be considered targets for managing blood lipids.
Maternal serum HDL-c, HDL2-c, and HDL3-c concentrations and HDL2-c/HDL3-c ratios in the first trimester in the AGA and LGA groups. a Maternal serum HDL-c, HDL2-c, and HDL3-c concentrations in the first trimester in the AGA and LGA groups. b The ratio of HDL2-c/HDL3-c in the AGA and LGA groups. AGA, appropriate for gestational age. LGA, large for gestational age. *P < 0.05, **P < 0.01
The incidence of LGA based on different maternal HDL-c, HDL2-c, and HDL3-c concentrations and HDL2-c/HDL3-c ratios in the first trimester. a The incidence of LGA based on different maternal HDL-c concentrations in the first trimester. b The incidence of LGA based on different maternal HDL2-c concentrations in the first trimester. c The incidence of LGA based on different maternal HDL3-c concentrations in the first trimester. d The incidence of LGA based on different maternal ratios of HDL2-c/HDL3-c in the first trimester. LGA, large for gestational age. AGA, appropriate for gestational age. *P value < 0.05, **P value < 0.01
Nomogram for the risk of LGA. To estimate the probability of LGA, the values of a pregnant woman value were marked at each axis. A straight line was drawn perpendicular to the point axis, and the points for all variables were summed. Next, the sum was noted on the total point axis, and a straight line was drawn perpendicular to the probability axis. LGA, large for gestational age. GWG, gestational weight gain. BMI, body mass index
Receiver operating characteristic curve for the prediction model. The area under the curve (AUC) was 0.663 (95% CI 0.593–0.732)
Background: Maternal lipid levels during pregnancy are critical for fetal development. Recent studies revealed that high-density lipoprotein cholesterol (HDL-c) levels during pregnancy were negatively correlated with birthweight. High-density lipoprotein 2 cholesterol (HDL2-c) is one of the major subclasses of HDL-c, and its relationship with birthweight is unclear. Association of HDL2-c concentration in the first trimester and risk of large for gestational age (LGA) was explored. Methods: This study recruited pregnant women who registered in Fuxing Hospital from October 2018 to January 2020, had regular obstetric examinations during pregnancy, and delivered between June 2019 and September 2020. Finally, 549 participants were recruited for the study. Maternal demographic characteristics and venous blood were collected at the 6th-14th gestational week, and serum total cholesterol (TC), triglyceride (TG), HDL-c, HDL2-c, high-density lipoprotein 3 cholesterol (HDL3-c), and low-density lipoprotein cholesterol (LDL-c) concentrations were detected. Neonatal characteristics were collected at delivery. A logistic regression model was used to explore the relationship between the first trimester HDL2-c concentration and LGA incidence. A nomogram was developed, and the performance was evaluated with a concordance index. Results: Seventy-five mothers delivered LGA infants, and the LGA incidence was 13.66%. LGA mothers had significantly lower serum HDL-c and HDL2-c concentrations than appropriate for gestational age (AGA) mothers. A logistic regression model showed that HDL2-c concentration was negatively correlated with LGA risk (odds ratio (OR) = 0.237, 95% confidence intervals (CI): 0.099-0.567, P = 0.001) when adjusted for age, prepregnancy body mass index (BMI), and parity. A nomogram was generated using all these risk factors. The area under the curve (AUC) was 0.663 (95% CI: 0.593-0.732). Conclusions: Maternal HDL2-c concentration in the first trimester was negatively correlated with the risk of LGA.
The level of serum IL-38 in NAFLD patients. a Comparison of serum IL-38 level in NAFLD cases and healthy control. b Comparison of serum IL-38 level in NAFLD patients with different ultrasonographic degrees. c Comparison of serum IL-38 level in NAFLD patients with abnormal liver enzymes or not
Correlation analyses between serum IL-38 levels with liver status, glucose metabolism and inflammation-related markers
ROC curve of serum IL-38 levels in diagnosing NAFLD
Background Insulin resistance, liver injury and dyslipidemia are reported in non-alcoholic fat liver disease (NAFLD) patients. Interleukin (IL)-38 may take part in the pathophysiology of insulin resistance. Nevertheless, the function of IL-38 in NAFLD is unknown. Herein, we determined whether serum IL-38 level might be utilised as a biochemical marker for diagnosing NAFLD. Methods NAFLD patients and healthy participants ( n = 91 each) were enrolled. Circulating serum IL-38 levels were detected using enzyme-linked immunosorbent assay. Other metabolic and inflammatory indices related to NAFLD were also assessed. Results Patients with NAFLD had higher serum IL-38 levels than healthy individuals. Significantly higher serum IL-38 levels were found in patients with severe and moderate NAFLD than in patients with mild NAFLD. IL-38 showed a significant correlation with parameters of insulin resistance, inflammation, and liver enzyme in NAFLD cases. Anthropometric, insulin resistance, inflammatory parameters, lipids and frequency of NAFLD showed significant differences among the serum IL-38 level tertiles. Participants in the 2nd and 3rd tertiles of serum IL-38 levels had a greater risk of NAFLD than those in the 1st tertile. Furthermore, IL-38 ROC curve showed a high area under ROC with 0.861. Conclusions It is possible for serum IL-38 to be a biomarker for NAFLD.
Background Pulmonary arterial hypertension (PAH) is a chronic, progressive lung vascular disease accompanied by elevated pulmonary vascular pressure and resistance, and it is characterized by increased pulmonary artery smooth muscle cell (PASMC) proliferation. Apolipoprotein A5 (ApoA5) improves monocrotaline (MCT)-induced PAH and right heart failure; however, the underlying mechanism remains unknown. Here we speculate that ApoA5 has a protective effect in pulmonary vessels and aim to evaluate the mechanism. Methods ApoA5 is overexpressed in an MCT-induced PAH animal model and platelet-derived growth factor (PDGF)-BB-induced proliferating PASMCs. Lung vasculature remodeling was measured by immunostaining, and PASMC proliferation was determined by cell counting kit‐8 and 5‐ethynyl‐2'‐deoxyuridine5‐ethynyl‐2'‐deoxyuridine incorporation assays. Coimmunoprecipitation-mass spectrometry was used to investigate the probable mechanism. Next, its role and mechanism were further verified by knockdown studies. Results ApoA5 level was decreased in MCT-induced PAH lung as well as PASMCs. Overexpression of ApoA5 could help to inhibit the remodeling of pulmonary artery smooth muscle. ApoA5 could inhibit PDGF-BB-induced PASMC proliferation and endoplasmic reticulum stress by increasing the expression of glucose-regulated protein 78 (GRP78). After knocking down GRP78, the protecting effects of ApoA5 have been blocked. Conclusion ApoA5 ameliorates MCT-induced PAH by inhibiting endoplasmic reticulum stress in a GRP78 dependent mechanism.
Flowchart for eligible participants in conducting the oral fat tolerance test. †Oral Fat Tolerance Test (OFTT), ‡ Magnetic Resonance Imaging (MRI)
Plasma triglyceride concentrations during an oral fat tolerance test (OFTT). a Comparison of Iraqi immigrants and native Swedes assessed as estimated marginal means (95% confidence interval). b Same as in a, restricted to participants with BMI 25–30 kg/m². a-b) Blue lines represent Iraqis, purple lines represent Swedes
Comparison of fat accumulation in various fat depots between Iraqi immigrants and native Swedes, estimated with magnetic resonance imaging (MRI). Boxplots of the magnetic resonance imaging (MRI)-estimated a liver proton density fat fraction (PDFF), b visceral adipose tissue (VAT) volume, c abdominal subcutaneous adipose tissue (SAT) volume and d VAT/abdominal SAT ratio. Shown are the boxplots of the estimated e intermuscular adipose tissue (IMAT) volume, f thigh SAT volume, g IMAT/thigh SAT ratio, and h) ratio between the concentration of intramyocellular lipids (IMCL) and water of the semitendinosus muscle of the left thighs
Example of MRI imaging. Examples of a acquired liver VIBE (in-phase image), b calculated liver PDFF, c acquired abdominal VIBE (fat image), d visceral (yellow) and subcutaneous (green) adipose tissue ROIs, e acquired thigh VIBE (in-phase image), f subcutaneous adipose tissue (green) and IMAT (yellow) ROIs, g calculated thigh PDFF images, and h a water-suppressed PRESS spectrum of the semitendinosus muscle
Subcutaneous adipose tissue analyses. The adipocyte-size distribution of fixed, intact subcutaneous adipose tissue was measured using a coulter counter, ~ 6000 counts/sample, and each sample was run in duplicate. a The graph displays the average distribution curves from n = 15 Iraqi and n = 8 Swedish subjects. b The fraction of small cells is defined to the left of the nadir (arrow), and the fraction of large cells is defined to the right of the nadir. c mRNA expression of COL1A1, LPL, SLC2A4, and CIDEA, measured by qPCR, n = 11–13 Iraqi and n = 8–11 Swedish subjects. Data are normalized to 18S expression
Purpose Previous studies have shown that at a similar body mass index, Middle Eastern immigrants are more insulin resistant and at higher risk for type 2 diabetes (T2D) than native Europeans. Insulin resistance is strongly associated with disturbed fat metabolism and cardiovascular disease (CVD). However, fat metabolism is poorly investigated comparing Middle Eastern and European ethnicities. Methods This observational study included 26 Iraqi and 16 Swedish-born men without T2D or clinical risk factors for CVD. An oral fat tolerance test (OFTT) was performed, where plasma triglycerides (p-TG) were measured for 6 h. mRNA expression and adipocyte size were measured in subcutaneous adipose tissue biopsies collected prior to OFTT, and magnetic resonance imaging was conducted to assess body fat distribution. Results The median p-TG accumulation was higher and the clearance slower among Iraqis than Swedes. None of the groups reached their fasting p-TG (Iraqis 1.55 mmol/l; Swedes 0.95 mmol/l) after 6 h (Iraqis p-TG 3.10 mmol/l; Swedes p-TG 1.50 mmol/l). Adipocyte size, mRNA expression, and fat accumulation in the liver, muscle and abdomen were similar in both groups. Conclusion Postprandial p-TG levels rather than fat distribution may reflect early signs of disturbed fat metabolism in Iraqi immigrants without CVD risk factors.
Background Inflammatory breast cancer (IBC) represents a deadly aggressive phenotype of breast cancer (BC) with a unique clinicopathological presentation and low survival rate. In fact, obesity represents an important risk factor for BC. Although several studies have identified different cellular-derived and molecular factors involved in IBC progression, the role of adipocytes remains unclear. Cancer-associated adipose tissue (CAAT) expresses a variety of adipokines, which contribute to tumorigenesis and the regulation of cancer stem cell (CSC). This research investigated the potential effect of the secretome of CAAT explants from patients with BC on the progression and metastasis of the disease. Methods This study established an ex-vivo culture of CAAT excised from IBC (n = 13) vs. non-IBC ( n = 31) patients with obesity and profiled their secretome using a cytokine antibody array. Furthermore, the quantitative PCR (qPCR) methodology was used to validate the levels of predominant cytokines at the transcript level after culture in a medium conditioned by CAAT. Moreover, the impact of the CAAT secretome on the expression of epithelial-mesenchymal transition (EMT) and cells with stem cell (CSC) markers was studied in the non-IBC MDA-MB-231 and the IBC SUM-149 cell lines. The statistical differences between variables were evaluated using the chi-squared test and unpaired a Student’s t -test. Results The results of cytokine array profiling revealed an overall significantly higher level of a panel of 28 cytokines secreted by the CAAT ex-vivo culture from IBC patients with obesity compared to those with non-IBC. Of note, interleukin-6 (IL-6), interleukin-8 (IL-8), and monocyte chemo-attractant protein 1 (MCP-1) were the major adipokines secreted by the CAAT IBC patients with obesity. Moreover, the qPCR results indicated a significant upregulation of the IL-6 , IL-8 , and MCP-1 mRNAs in CAAT ex-vivo culture of patients with IBC vs. those with non-IBC. Intriguingly, a qPCR data analysis showed that the CAAT secretome secretions from patients with non-IBC downregulated the mRNA levels of the CD24 CSC marker and of the epithelial marker E-cadherin in the non-IBC cell line. By contrast, E-cadherin was upregulated in the SUM-149 cell. Conclusions This study identified the overexpression of IL-6 , IL-8 , and MCP-1 as prognostic markers of CAAT from patients with IBC but not from those with non-IBC ; moreover, their upregulation might be associated with IBC aggressiveness via the regulation of CSC and EMT markers. This study proposed that targeting IL-6, IL-8, and MCP-1 may represent a therapeutic option that should be considered in the treatment of patients with IBC.
Study Flowchart
Kaplan–Meier cumulative survival curves for cardiovascular death
Kaplan–Meier cumulative survival curves for noncardiovascular death
Background Familial hypercholesterolemia (FH) is a codominant autosomal disease characterized by high low-density lipoprotein cholesterol (LDLc) and a high risk of premature cardiovascular disease (CVD). The molecular bases have been well defined, and effective lipid lowering is possible. This analysis aimed to study the current major causes of death of genetically defined heterozygous familial hypercholesterolemia (heFH). Methods A case‒control study was designed to analyse life-long mortality in a group of heFH and control families. Data from first-degree family members of cases and controls (nonconsanguineous cohabitants), including deceased relatives, were collected from a questionnaire and review of medical records. Mortality was compared among heFH patients, nonheFH patients, and nonconsanguineous family members. Results A total of 813 family members were analysed, 26.4% of whom were deceased. Among the deceased, the mean age of death was 69.3 years in heFH individuals, 73.5 years in nonheFH individuals, and 73.2 years in nonconsanguineous individuals, without significant differences. CVD was the cause of death in 59.7% of heFH individuals, 37.7% of nonheFH individuals, and 37.4% of nonconsanguineous individuals (P = 0.012). These differences were greater after restricting the analyses to parents. The hazard ratio of dying from CVD was 2.85 times higher (95% CI, (1.73–4.69) in heFH individuals than in individuals in the other two groups (non-FH and nonconsanguineous), who did not differ in their risk. Conclusions CVD mortality in heFH individuals is lower and occurs later than that described in the last century but is still higher than that in non-FH individuals. This improved prognosis of CVD risk is not associated with changes in non-CVD mortality.
Relationship between dyslipidemia and GVHD (designed with BioRender). A: Preconditioning results in tissue damage, releasing of various inflammatory factors, expansion, and differentiation of T cells. B: GVHD leads to a decrease in serum HTGL content, makes triglyceride fail to break down, and ultimately develops hypertriglyceridemia. Increased LP-X content leads to cholestasis, blocks cholesterol excretion, and eventually leads to hyperlipidemia. C: Extensive immune expansion can result in hypoproteinemia and hyperlipidemia. D: GVHD alters the intestinal microenvironment and affects the synthesis of enzymes that regulate substances
Targets of lipid-lowering drugs (designed with BioRender)
Dyslipidemia is one of the complications after allogeneic hematopoietic stem cell transplantation (allo-HSCT), and it is often underestimated and undertreated. Dyslipidemia in allo-HSCT recipients has been confirmed to be associated with endocrine dysfunction, acute and chronic graft-versus-host disease (aGVHD and cGVHD), immunosuppressive agent application, etc. However, few studies have illustrated the accurate molecular signaling pathways involved in dyslipidemia, and there are no standard guidelines for dyslipidemia management after HSCT. This review will discuss the pathogenesis of dyslipidemia, especially the association with aGVHD and/or cGVHD. Comprehensive treatment methods for dyslipidemia after HSCT will also be summarized.
Background The role of lipid metabolism in obesity and cancer manifestations cannot be underestimated, but whether alterations in lipid metabolism can manipulate the vasculature to promote obesity among breast cancer (BC) survivors is yet to be clearly understood. This study quantified plasma lipid and particle sizes using high-throughput proton (¹H) nuclear magnetic resonance (NMR) and tested their associations with obesity among breast cancer (BC) survivors. Methods A total of 348 (225 premenopausal and 123 postmenopausal) BC survivors enrolled from five hospitals in Korea were included. We assessed thirty-four plasma lipid biomarkers using ¹H NMR, and obesity status was defined as a body mass index (BMI) of 25 kg/m² or greater. Generalized linear and logistic regression models were applied to estimate the least-square means of BMI (kg/m²) and odds ratio (OR)s of obesity, respectively, and the corresponding 95% confidence interval (CI)s across plasma lipid levels. Results Mean (SD) values of BMI was 23.3 (3.2) kg/m² and 90 (25.9%) had BMI of ≥ 25 kg/m². BMI levels increased with increasing total triglycerides (TG), TG in lipoproteins and very-low-density lipoprotein (VLDL) subfractions. However, BMI levels decreased with increasing tertiles of high-density lipoprotein (HDL)-cholesterol (C) and HDL particle size (HDL-p). Similar associations were observed in the logistic regression models. The increasing and decreasing BMI trends with TG and HDL profiles respectively were predominantly limited to premenopausal BC survivors. Conclusions Increasing levels of plasma total TG and TG in lipoproteins were associated with increasing levels of BMI among premenopausal BC survivors. High HDL-C levels and large HDL-p were inversely associated with obesity among premenopausal BC survivors. Due to the cross-sectional design of this study, longitudinal studies are necessary to examine the association between obesity and lipid profile among BC survivors.
Mean values (black dot) and absolute ranges (error bars) for total cholesterol for HIV-uninfected participants who were on CLDs(A) or not on CLDs(B), vs. HIV-infected participants on CLDs(C), or not on CLDs(D). *absolute maximum value of marker filled outside range of X axis
Mean values (black dot) and absolute ranges (error bar) for triglycerides for HIV-uninfected participants who were on CLDs(A) or not on CLDs(B), vs. HIV-infected participants on CLDs(C), or not on CLDs(D). *absolute maximum value of marker filled outside range of X axis
Mean values (black dot) and absolute ranges (error bar) for HDL-cholesterol for HIV-uninfected participants who were on CLDs(A) or not on CLDs(B), vs. HIV-infected participants on CLDs(C), or not on CLDs(D). *absolute maximum value of marker filled outside range of X axis
Mean values (black dot) and absolute ranges (error bar) for LDL-cholesterol for HIV-uninfected participants who were on CLDs(A) or not on CLDs(B), vs. HIV-infected participants on CLDs(C), or not on CLDs(D). *absolute maximum value of marker filled outside range of X axis
Background To assess the long-term biological coefficient of variation within individuals (CVI) and between individuals (CVG), effect of aging and cholesterol lowering drugs on blood levels of lipids in HIV-1-infected and -uninfected men. Methods Bloods were analyzed every six months over 17 years for total cholesterol (TC), triglycerides (TGs), high-density lipoprotein cholesterol (HDL-C) and low-density lipoprotein cholesterol (LDL-C) in 140 HIV-uninfected (38–66 years old) and 90 HIV-treated infected (48–64 years old) white Caucasian men to examine CVI, CVG, and the effect of cholesterol lowering drugs (CLDs) on lipid levels, and estimated changes per year of biomarkers. Results With exception of HDL-C, the long term CVI compared with CVG were higher for serum levels of TC, TGs, and LDL-C in both HIV-1 infected and uninfected men not taking CLDs. Excluding results of TGs in HIV positive men, the CVI compared with CVG were lower for serum levels of TC, HDL-C, and LDL-C in both groups not taking CLDs. There were significant (p < 0.05) differences in the median serum values of lipid biomarkers among 77 HIV negative men taking and 63 not taking CLDs. Also, with exception of HDL, there were significant (p < 0.05) differences in the median values of TC, TGs and LDL-C among 28 HIV positive men taking or not taking CLDs. Conclusion Long term CVI and CVG of biomarkers will be useful for monitoring antiviral therapy side effects on lipid profiles in HIV-infected men. CVI of HIV-infected men for TC, TGs, HDL, LDL were higher significantly than CVI of HIV-uninfected men. Interestingly the long term CVI were higher than CVG for the men, who were on CLDs compared to men not on CLDs. The long-term pattern of CVI and CVG of lipid markers in both HIV-infected and uninfected men on CLDs differed from their short-term pattern.
Intensive BP control and primary outcome according to AIP quartiles. *pr: person year. Model was adjusted for all covariates in Model 3 except treatment arm
Background Literature on the association between the atherogenic index of plasma (AIP) and the risk of major adverse cardiovascular events (MACEs) among non-diabetic hypertensive older adults is quite limited. Methods A post-hoc analysis of data obtained from the Systolic Blood Pressure Intervention Trial was performed. The predictive value of AIP on the risk of MACEs among non-diabetic hypertensive older adults was assessed to evaluate whether the benefit of intensive blood pressure (BP) control in preventing MACEs is consistent in different AIP subgroups. Results In this study, 9323 participants with AIP were included, out of which 561 (6.02%) had composite cardiovascular outcomes during a median of 3.22 years of follow-up. Patients in the highest AIP quartile had a significantly increased risk of the primary outcome. In the fully adjusted Model 3, the adjusted hazard ratios (HRs) of the primary outcome for participants in Q2, Q3, and Q4 of AIP were 1.32 (1.02, 1.72), 1.38 (1.05, 1.81), and 1.56 (1.17, 2.08) respectively. Consistently, the trend test for the association between AIP quartiles and the primary outcome showed that a higher AIP quartile was associated with a significantly higher risk of the primary outcome (adjusted HR (95%CI) in model 3:1.14 (1.04, 1.25), P = 0,004). However, within each AIP quartile, absolute event rates were lower in the intensive treatment group. No evidence was found for the interaction between intensive BP control and AIP for the risk of the primary outcome (P for interaction = 0.932). Conclusion This study found that elevated AIP was independently and positively associated with the risk of MACEs among non-diabetic hypertensive older adults. The benefits of intensive BP control in managing cardiovascular events were consistent in different AIP subgroups.
Flow chart
Background: Trimethylamine N-oxide (TMAO)-related metabolites are associated with the pathogenesis of atherosclerotic cardiovascular disease (ASCVD) and are known to disrupt lipid metabolism. The aims of this study were to evaluate the associations between TMAO-related metabolites and blood lipids and determine how lowering the lipid profile via rosuvastatin therapy influences TMAO-related metabolites. Methods: A total of 112 patients with suspected ASCVD were enrolled in this study. The levels of plasma TMAO-related metabolites, including TMAO, choline, carnitine, betaine, and γ-butyrobetaine (GBB), were analyzed by stable isotope dilution liquid chromatography-tandem mass spectrometry (LC/MS/MS) before and after rosuvastatin therapy in all patients. Statistical methods were used to detect the associations between TMAO-related metabolites and blood lipids and determine how rosuvastatin therapy alters the levels of these metabolites. Results: A significant positive correlation was found between TMAO and triglycerides (TG) (r = 0.303, P < 0.05). Furthermore, significant negative correlations were found between TMAO and high-density lipoprotein cholesterol (HDL-c) and between betaine and low-density lipoprotein cholesterol (LDL-c) (r = - 0.405 and - 0.308, respectively, both P < 0.01). Compared to baseline, significantly lower TMAO levels and higher carnitine, betaine and GBB levels were observed after rosuvastatin therapy, while the lipids decreased significantly (P < 0.05). The significant correlation between TMAO and TG or between betaine and LDL-c disappeared after rosuvastatin therapy (r = 0.050 and - 0.172, respectively, both P > 0.05). However, a significantly positive association between carnitine and TC and a negative association between carnitine and LDL-c or between betaine and TG were found after adjustment for sex, age, body mass index (BMI) and lipids (P < 0.05). Conclusions: This study suggests that TMAO-related metabolites are significantly associated with blood lipids, although some of them are changed postrosuvastatin therapy. Lower TMAO and higher TMAO precursors were observed after rosuvastatin therapy compared to baseline. This study indicates that elevated TMAO precursors after rosuvastatin therapy and their potential impact on ASCVD should be considered in the clinic.
Baseline concentrations of biomarkers in participants according to whether their left ventricular ejection fraction declined or not over the study follow-up
Background It is important to identify patients at increased risk of worsening of left ventricular ejection fraction (LVEF) after a myocardial infarction (MI). We aimed to identify the association of various potential biomarkers with LVEF impairment after an MI in South American patients. Methods We studied adult patients admitted to a University Hospital and diagnosed with an acute MI. Plasma concentrations of high-sensitivity C-reactive protein (hsCRP), proprotein convertase subtilisin/kexin type 9 (PCSK9), N-terminal prohormone of brain natriuretic peptide (NT-proBNP) and heart-type fatty-acid-binding protein (FABP3) were determined in samples drawn shortly after the event. Participants had a follow-up visit at least 45 days after the event. The primary endpoint was defined as any decline in LVEF at follow-up relative to baseline. Results The study included 106 patients (77.4% men, 22.6% women), mean age was 64.1, mean baseline LVEF was 56.6, 19% had a prior MI. We obtained a follow-up evaluation in 100 (94.4%) of participants, mean follow-up time was 163 days. There was a significant correlation between baseline PCSK9 and hsCRP (r = 0.39, p < 0.001). Baseline hsCRP concentrations were higher in patients who developed the endpoint than in those who did not (32.1 versus 21.2 mg/L, p = 0.066). After multivariate adjustment, baseline PCSK9, male sex and age were significantly associated with impairment in LVEF. The absolute change in LVEF was inversely correlated with baseline hsCRP (standardized coefficient = − 0.246, p = 0.004). Conclusion High plasma levels of PCSK9 and hsCRP were associated with early decreases in LVEF after an MI in Latin American patients.
Diagram of patients selection. Abbreviations: FPG, fasting blood glucose; 2hPG, 2 h postprandial blood glucose; HbA1c, glycosylated hemoglobin; T2DM, type 2 diabetes mellitus; CAD, coronary artery disease
Restricted cubic spline model of the odds ratios of CAD with serum GDF-15 and ApoB to ApoA1 ratio in T2DM patients. The dashed lines represent the 95% confidence intervals. GDF-15: serum growth differentiation factor 15; Apo B, apolipoproteins B; Apo A1, apolipoproteins A1. Both serum GDF-15 levels and ApoB/ApoA1 ratio were positively correlated with CAD
Background Clinical investigations have found that there was a close association between T2DM and adverse cardiovascular events, with possible mechanisms included inflammation, apoptosis, and lipid metabolism disorders. High serum GDF-15 concentration and the apolipoprotein B/apolipoprotein A1 ratio (ApoB/ApoA1) are involved in the above-mentioned mechanisms and are thought to be related to the occurrence of adverse cardiovascular events. However, it remains unclear whether circulating GDF-15 levels and the ApoB/ApoA1 ratio are related to T2DM patients with CAD. Methods T2DM patients with or without CAD were eligible for this study. According to the inclusion and exclusion criteria, 502 T2DM patients were enrolled between January 2021 and December 2021 and were then divided into T2DM group ( n = 249) and CAD group ( n = 253). The ApoB, ApoA1 and GDF-15 concentrations were measured at hospital admission and the ApoB/ApoA1 ratio was then calculated. Results Compared with T2DM group, serum GDF-15 levels and ApoB/ApoA1 ratio increased in CAD group. Furthermore, a positive relationship between the occurrence of CAD in diabetic population and circulating GDF-15 concentrations and ApoB/ApoA1 ratio was observed in logistic regression analysis ( p < 0.01). Restrictive cubic spline analysis after adjusted for multiple risky variables showed that serum GDF-15 or ApoB/ApoA1 ratio correlated positively with CAD. Conclusions Circulating GDF-15 levels and serum ApoB/ApoA1 ratio vary in CAD group and T2DM group. ApoB/ApoA1 and GDF-15 may be helpful for predicting the occurrence of CAD in patients with T2DM.
The association between high density lipoprotein-cholesterol (HDL-c level) and pancreatic neuroendocrine neoplasm (PNEN) grades. A The proportion of G2/G3 PNENs decreased with the increase of HDL-c level; B, C The proportion of high-grade PNENs (G2/G3 (B); G3 (C)) in low HDL-c was more common than those with high HDL-c level
Receiver operating characteristic analysis to differentiate the high grade pancreatic neuroendocrine neoplasms (PNENs) from the low grade PNENs. A Performance of high density lipoprotein-cholesterol (HDL-c) combined with age and tumor size in recognizing G1 tumor from G2/G3 tumor; B Performance of tumor size alone, HDL-c combined with tumor size, HDL-c combined with age and tumor size in recognizing G1/G2 tumor from G3 tumor
The high density lipoprotein-cholesterol (HDL-c) levels in pancreatic neuroendocrine neoplasms patients with and without lymph invasion, organs invasion, vascular invasion and neural invasion
Background The role of serum high-density lipoprotein cholesterol (HDL-c) in tumorigenesis are observed in several endocrine-related cancers. However, its role in pancreatic neuroendocrine neoplasms (PNENs) has not been understood. In the current study, the relationship between HDL-c levels and malignant behavior in PNENs was explored. Methods One hundred ninety-seven patients with histopathology confirmed PNENs were included. PNENs were divided into three grades (G1, G2 and G3) as 2017 WHO classification based on ki67 index and mitosis count. The demographic data, clinical information, tumor morphological and pathological features (organs invasion, lymph node metastasis, vascular invasion and perineural invasion), and serum tumor biomarkers were collected. The relationships between HDL-c levels and malignant behaviors in PNENs were analyzed using logistic regression analysis. Models were also developed for the identification of high grade PNENs. Results The levels of serum HDL-c in G2/G3 tumor were significantly lower than that in G1 tumor ( P = 0.031). However, no such difference was found between G3 and G1/G2. The proportions of low HDL-c (≤ 0.9 mmol/L) were higher in high-grade PNENs (G2/G3 or G3) than those in low-grade (G1 or G1/G2) (29.0 vs 15.2%, P = 0.032; 37.0 vs 20.5%, P = 0.023). The risk of G2/G3 tumors in patients with high serum HDL-c levels was decreased (odds ratio (OR) = 0.35, 95% confidence interval (CI): 0.12–0.99). Similarly, the risk of G3 PNENs increased in patients with low HDL-c levels (OR = 2.51, 95%CI:1.12–5.60). HDL-c level was also associated with a high ki67 index (> 55%) (OR = 0.10, 95%CI: 0.02–0.51) and neuroendocrine carcinoma G3 (OR = 0.21, 95%CI: 0.06–0.80). The area under the curve (AUC) of HDL-c + tumor size + age was 0.85 (95% CI: 0.79–0.91) in identifying G2/G3 PNENs, and HDL-c (> 0.9 mmol/L) + tumor size + age had an AUC of 0.77 (95% CI: 0.70–0.84) in identifying G3 PNENs. HDL-c level was associated with lymph node metastasis (OR = 0.24, 95%CI:0.08–0.99). Conclusion Serum HDL-c levels were significantly associated with malignant behaviors in PNENs, in particular to tumor grade and lymph node metastasis.
Background The incidence rate of metabolic-associated fatty liver disease (MAFLD) is increasing annually; however, there are still no effective methods for establishing an early diagnosis and conducting real-time tracing. Vaspin can affect the metabolic processes in the body, and it is closely associated with many metabolic diseases. Many previous studies have speculated on the association between vaspin and MAFLD, but the results of these studies have not been conclusive. This meta-analysis examined the differences in circulating vaspin levels between patients with MAFLD and healthy individuals. Methods Six databases and other sources were searched with free terms and Medical Subject Headings terms, and a total of 13 articles were included (900 cases and 669 controls). RevMan 5.3 and Stata 16 were used for analysis. The standardised mean difference (SMD) and 95% confidence interval (CI) were used to assess the overall outcomes. Cohen’s kappa coefficient was applied to examine the differences between the two authors in the selection of studies and in the evaluation of the quality of evidence for the studies. Results The results demonstrated that there was no significant difference in the circulating vaspin levels between the MAFLD group and healthy group (SMD = 0.46, 95% CI: [− 0.12, 1.04]). The subgroup analysis suggested that area and body mass index (BMI) may be the sources of heterogeneity, and the results of univariate meta-regression analysis were consistent with those of the subgroup analysis (P = 0.005 and P < 0.001, respectively). Furthermore, BMI may better explain the source of heterogeneity (P = 0.032) in the multivariate meta-regression analysis. Conclusion In summary, no significant correlation was observed between the circulating vaspin levels and MAFLD. BMI may be an important factor affecting this correlation, which may provide a reference for further studies on mechanism and diagnosis of MAFLD.
Flowchart with selection of study participants. The process of selecting study participants. HeFH, heterozygous familial hypercholesterolemia; LDLR, low-density lipoprotein recepter
Time to incident cancer. Cumulative incidence illustration of cancer disease in both groups of relatives and the general population
Background Heterozygous familial hypercholesterolemia (HeFH) due to low-density lipoprotein receptor (LDLR) mutations predisposes patients to highly elevated levels of cholesterol, and patients are at increased risk of adverse cardiovascular events and other morbidities. Whether the LDLR mutation and high cholesterol levels affect the risk of cancer remains unknown. The purpose of the present study was to assess the long-term cancer risk in HeFH relatives. Methods Study participants were identified by cascade screening during 1992–1994. A comparison cohort was matched 10:1 to the relatives from the Danish general population based on birth year, gender and address. All participants were followed until a cancer diagnosis, migration, death, or end of follow-up as of December 31, 2019. The primary endpoint was any incident cancer diagnosis. Results In total, we included 221 relatives with a median age of 37 years (interquartile range: 27–53 years). A total of 117 (53%) of the relatives carried a LDLR gene mutation. The crude hazard ratio of our primary endpoint did not reveal any differences in cancer incidence in mutation-carrying relatives compared with the general population cohort (1.18; 95% CI, 0.81–1.71). Nonmutation-carrying relatives however had a lower cancer incidence than the general population (0.45: 95% CI, 0.26–0.80). Thus, the risk among mutation-carrying HeFH relatives compared with nonmutation-carrying HeFH relatives was increased (HR: 2.39; 95% CI, 1.24–4.61). Conclusion In Denmark, LDLR mutation-carrying HeFH relatives did not have a different cancer risk than the general population. In contrast, nonmutation-carrying relatives had a lower risk of cancer.
Dynamic nomogram of the diagnostic model
Importance score of different variable
ROC curves of TG, TG/HDL-C, TyG, TyG-BMI, HSI, and the Model for MAFLD
Calibration plot of the model
DCA curves of the model
Background The triglyceride and glucose index (TyG) and triglyceride to high-density lipoprotein cholesterol ratio (TG/HDL-C) are substitute markers of insulin resistance (IR). In a retrospective cross-sectional study, the authors aimed to compare the efficacy of the two indicators in diagnosing metabolic-associated fatty liver disease (MAFLD) to construct a novel disease diagnosis model. Methods Overall, 229 patients (97 MAFLD and 132 Non-MAFLD at West China Hospital of Sichuan University were included. MAFLD was diagnosed using ultrasonography. Biochemical indexes were collected and analyzed by logistic regression to screen out indicators that were expressed differently in MAFLD patients and healthy controls, which were incorporated into a diagnostic model. Results After adjusting for age, sex, and body mass index (BMI), serum alanine transaminase (ALT), aspartate transaminase (AST), AST/ALT (A/A), fasting plasma glucose (FPG), cystatin C (Cys-C), uric acid (URIC), triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), alkaline phosphatase (ALP), gamma-glutamyl transferase (GGT), non-HDL-C, LDL-C/HDL-C, non-HDL-C/HDL-C, TG/HDL-C, TC/HDL-C, TyG, and TyG-BMI were risk factors for MAFLD. The odds ratio of TG/HDL-C and TyG were 5.629 (95%CI: 3.039–10.424) and 182.474 (95%CI: 33.518–993.407), respectively. In identifying MAFLD, TyG, TyG-BMI, TG, and TG/HDL-C were found to be the most vital indexes based on the random forest method, with the area under the curve (AUC) greater than 0.9. In addition, the combination of BMI, ALT, and TyG had a high diagnostic efficiency for MAFLD. Conclusions TyG and TG/HDL-C were potential risk factors for MAFLD, and the former performed better in diagnosing MAFLD. The combination of BMI, ALT, and TyG improved the diagnostic capability for MAFLD.
Background MicroRNAs (MiRNAs) are known to participate in preadipocyte differentiation, but the manner in which miR-146a-5p participates in this process remains unclear. This study was performed to examine the participation of miR-146a-5p in 3T3-L1 cell differentiation. Material and Methods miR-146a-5p expression was upregulated and down-regulated to examine effects on 3T3-L1 cell differentiation. Bioinformatics analysis was performed to predict its target genes, and the signaling pathway it regulates was identified by qRT-PCR and Western blotting. The expression of miR-146a-5p in epididymal adipose tissue from obese mice and in an obese mouse adipose cell model was examined by qRT-PCR. Results 3T3-L1 cells differentiated into mature adipocytes successfully, as verified by increased areas of intracellular lipid droplets and elevated expression of mature adipocyte markers, and these cells had elevated miR-146a-5p expression. The intracellular lipid droplet and triglyceride contents and the expression of mature adipocyte markers were significantly increased in miR-146a-5p–overexpressing 3T3-L1 cells and markedly decreased in miR-146a-5p–inhibited 3T3-L1 cells. ErbB4 was a predicted target gene of miR-146a-5p. In miR-146a-5p–overexpressing 3T3-L1 cells, ErbB4 expression and ERK1/2 phosphorylation were decreased and the expression of PPAR-γ was increased; the opposite was observed in miR-146a-5p–inhibited 3T3-L1 cells. In addition, miR-146a-5p expression was significantly increased in the mouse epididymal adipose tissue and adipose cell model. Conclusions Upregulated miR-146a-5p expression was related to 3T3-L1 cell differentiation. MiR-146a-5p promoted 3T3-L1 cell differentiation by targeting ErbB4 and via the ERK1/2/PPAR-γ signaling pathway.
Background An excessive rise in maternal lipids during pregnancy may have detrimental impacts on maternal and fetal health leading to adverse pregnancy outcomes. However, knowledge gaps exist with respect to the association between lipid biomarkers and birth outcomes. Methods We conducted a secondary data analysis of healthy pregnant women (N = 25) with mid-pregnancy fasting serum samples collected at 22–28 weeks of gestation and birth outcome data. Serum was analyzed for conventional lipid profile (total-C, HDL-C, LDL-C, and triglycerides) and lipoprotein subclass distribution, including particle number (nM) and size (nm), for very low-density lipoprotein (VLDL)/chylomicron (CM), low density lipoprotein (LDL), and high-density lipoprotein (HDL), by nuclear magnetic resonance spectroscopy. Associations between maternal lipids and birth outcomes, including birth weight (g) and gestational age (weeks), were assessed using multivariable linear regression, adjusted for pre-pregnancy BMI. Results Although conventional lipids were not associated (p > 0.05) with birth outcomes, every 1-unit increment in large VLDL/CM particles (nM) and VLDL/CM size (nm) was associated with an increase in birth weight (confounder-adjusted β-coefficient, 45.80 g [5.30, 86.20, p = 0.003] and 24.90 g [8.80, 40.90, p = 0.002], respectively). Among the HDL subclass parameters, a 1-unit (nM) increase in the concentration of total HDL-particles was associated with a reduced birth weight (confounder adjusted β-coefficient, -19.40 g [95% confidence interval, -36.70, -2.20]; p = 0.03) after adjustment for maternal pre-pregnancy BMI. Conclusion The preliminary results of this pilot study suggest that total particle concentrations of VLDL/CM and HDL in mid-pregnancy have divergent associations with birth weight, potentially reflecting the specific roles of these lipoprotein particles with respect to placental function and fetal growth.
Background The severity of metabolic dysfunction-associated fatty liver disease (MAFLD) reportedly plays a part in the etiology of colorectal tumors. However, there is no consensus. Methods Studies relevant with the impact of MAFLD severity on the risk of colorectal neoplasms published before 24th April 2022 were screened. The pooled odds ratio (OR) with corresponding 95% confidence intervals (95% CI) was obtained using standard and cumulative meta-analyses. Subgroup, meta-regression, and sensitivity analyses were carried out to identify heterogeneity. Results Fourteen studies with data from 37,824 MAFLD patients were included. The prevalence of colorectal neoplasms escalated with the progression of MAFLD compared to simple steatosis (OR = 1.93; 95% CI = 1.42–2.62). The magnitude and direction of the effect on these outcomes remained largely constant over time. Even after limiting the meta-analysis to 8 studies with available adjusted OR (aOR), the findings still suggested that MAFLD severity was positively related to colorectal neoplasms (aOR = 3.03; 95% CI = 2.02–4.53). Severe MAFLD was more likely to cause left colon tumors (OR = 3.86, 95% CI = 2.16–6.91) than right colon neoplasms (OR = 1.94, 95% CI = 1.15–3.28). Conclusion The severity of MAFLD was independently related to colorectal neoplasms and severe MAFLD was more likely to cause left colon tumors.
Chemical compositions of lipoproteins
Preeclampsia (PE) is a multisystemic syndrome specific to pregnancy. Although PE is the leading cause of death from complications associated with pregnancy, its aetiology is still unknown. In PE, lipid metabolism is altered. When lipids are damaged, both the mother and the foetus may be at risk. Lipoproteins contain apolipoproteins, triacylglycerols, free and esterified cholesterol, and phospholipids, all of which are susceptible to oxidative stress when high levels of oxygen and nitrogen free radicals are present. Lipoperoxidation can occur in three stages: mild, moderate, and severe. In severe lipid damage, highly toxic products such as malondialdehyde (MDA) can be generated; under these conditions, low-density lipoprotein (LDL) proteins can be oxidized (oxLDL). oxLDL is a biomolecule that can affect the production of nitric oxide (NO), the main vasodilator derived from the endothelium. oxLDL can interfere with the transduction of the signals responsible for triggering the activation of endothelial nitric oxide synthase (eNOS), causing reduced vasodilation and endothelial dysfunction, which are the main characteristics of preeclampsia. The objective of the review was to analyse the information the current information about exists about the impact generated by the oxidation of LDL and HDL lipoproteins in neonates of women with preeclampsia and how these alterations can predispose the neonate to develop diseases in adulthood. PE can cause foetal loss, intrauterine growth restriction, or developmental complications. Neonates of mothers with PE have a high risk of cardiovascular diseases, stroke, mental retardation, sensory deficiencies and an increased risk of developing metabolic diseases. PE not only affects the foetus, generating complications during pregnancy but also predisposes them to chronic diseases in adulthood.
Background Hypertriglyceridemic-waist (HTGW) phenotype has been proposed as a practical tool for screening the risk of cardiovascular diseases and glycemic metabolic disease. This study sought to investigate the relationship between HTGW phenotype and non-alcoholic fatty liver disease (NAFLD). Methods A total of 14,251 subjects who took part in health screening were enrolled in the study and NAFLD was diagnosed by abdominal ultrasound. According to triglyceride (TG) and waist circumference, the study population was divided into four phenotypes, in which HTGW phenotype was defined as TG ≥ 1.7 mmol/L and male waist circumference ≥ 90 cm or female waist circumference ≥ 80 cm. Multivariate logistic regression analysis was used to evaluate the relationship between HTGW phenotype and NAFLD. Results In the current study, 2.43% of the subjects had HTGW phenotype, while the prevalence of NAFLD in subjects with HTGW phenotype was 77.81%. After full adjustment for covariates, compared with people with normal waist circumference and TG levels, the risk of NAFLD in people with normal TG levels but enlarged waist circumference increased by 39% [OR:1.39, 95%CI: 1.15, 1.68], in people with normal waist circumference but elevated TG levels increased by 96% [OR:1.96, 95%CI: 1.65, 2.33], and in subjects with HTGW phenotype increased by 160% [OR:2.60, 95%CI: 1.88, 3.58]. Additionally, further analysis suggested that there were significant interactions between age, height, BMI and NAFLD risk associated with TGW phenotypes. Receiver operating characteristic curves analysis suggested that the combination of TG and waist circumference further improved the diagnostic value for NAFLD. Conclusions HTGW phenotype is associated with NAFLD risk in the general population, which may be a novel and accessible indicator for NAFLD screening.
Flow chart of the HTG-AP patient selecttion. The 24 h, 48 h, 3-4 d, and 5-7 d groups were classified by the duration between the time of onset to when the TG levels were first measured. HTG-AP, hyperlipidaemic-induced acute pancreatitis; TG, triglyceride
Cross-sectional study: TG levels significantly decreased and attenuated the association with disease severity in the HTG-AP patients. A The comparison of TG levels in g24 h, g48 h, g3-4 d, g5-7 d groups. B The comparison of TG levels in MAP, MSAP and SAP patients in g24 h, g48 h, g3-4 d, g5-7 d groups respectively. Data are presented as medians (IQR, 25th-75th percentile). g24 h, g48 h, g3-4 d, g5-7 d groups are based on the duration between the time of onset to when first measured TG levels in HTG-AP patients, represent 24 h group, 48 h group, 3-4 d group, and 5-7 d group respectively. HTG-AP, hypertriglyceridaemia-induced acute pancreatitis; TG, triglyceride; MAP/MSAP/SAP, mild/moderately severe/severe AP; IQR, interquartile range. * indicates significance when compared among g24 h, g48 h, g3-4 d (P < 0.050). § indicates significance when compared with MAP disease (P < 0.050)
ROC curves of TG levels for predicting MSAP/SAP diseases in HTG-AP patients. A ROC curve of TG levels for predicting MSAP/SAP diseases in HTG-AP in all cross-sectional subjects. B ROC curves of TG levels for predicting MSAP/SAP diseases in HTG-AP in the different onset time groups. g24 h, g48 h, g3-4 d, g5-7 d groups based on the duration between the time of onset to when the TG levels were first measured in HTG-AP patients. ROC, receiver-operating characteristic; HTG-AP, hypertriglyceridaemia-induced acute panceatitis; TG, triglyceride; MSAP/SAP, moderately severe/severe AP
Longitudinal study: TG levels remarkably declined, and the correlation with disease severity weakened over time in the HTG-AP patients. A The TG level changed after the onset of symptoms from 24 h to 5-7 d. B The difference in TG levels in MAP, MSAP and SAP patients during the onset time of 24 h to 5-7 d. Data are presented as the medians (IQR, 25th-75th percentile). The 24 h, 48 h, 3-4 d, and 5-7 d are based on duration between the time of onset to when the TG levels were measured in HTG-AP patients. TG, triglyceride; HTG-AP, hypertriglyceridaemia-induced acute pancreatitis; MAP/MSAP/SAP, mild/moderately severe/severe AP; IQR, interquartile range. * significance when compared among different onset times (P < 0.050). §§ significance for both in MSAP and SAP disease when compared with MAP disease (P < 0.050). § significance only for SAP disease when compared with MAP disease (P < 0.050)
Background: The association of serum triglyceride (TG) levels with the severity of hypertriglyceridaemia-induced acute pancreatitis (HTG-AP) remains controversial. This study aimed to comprehensively assess the TG levels from the initial onset and their predictive value in the disease assessment of HTG-AP. Methods: Data collected from January 2018 to July 2021 in one institute were assessed retrospectively. HTG-AP was defined as a TG level > 500 mg/dL in the absence of other common aetiologies of AP. The TG levels within 24 hours (24 h), 48 hours (48 h), 3-4 days (3-4 d), and 5-7 days (5-7 d) after symptom onset and their correlations with disease severity in HTG-AP patients were analysed by cross-sectional and longitudinal studies. Results: In the cross-sectional study, 377 HTG-AP patients were included before lipid-lowering intervention: 216 subjects had their first TG levels measured within 24 h after onset, 91 within 48 h, 50 in 3-4 d, and 20 in 5-7 d. TG levels decreased in the 24 h, 48 h and 3-4 d groups (P < 0.001), however, the TG decline in the 5-7 d group had no difference compared with the 3-4 d group. HTG-AP patients with severe or moderately severe disease displayed higher TG levels than those with mild disease in the 24 h and 48 h groups (P < 0.050) but not in the 3-4 d or 5-7 d groups. Furthermore, the TG levels were correlated with the modified computed tomography severity index only in the 24 h and 48 h groups, while an association between serum calcium levels and C-reactive protein levels was only present in the 24 h group. Similarly, the TG levels were related to hospital days and ICU days in the 24 h and/or 48 h groups. In the longitudinal study, 165 patients with complete records of TG levels from 24 h to 5-7 d were enrolled. With supportive care and lipid-lowering treatment after admission, the TG levels declined rapidly (P < 0.001), and the correlations with disease severity weakened or even disappeared from 24 h to 5-7 d. Conclusion: TG levels decreased and attenuated the association with disease severity of HTG-AP over the time of onset. The TG levels within the initial 48 h after onset were most useful for the diagnosis and disease assessment of HTG-AP.
Flow chart of study selection for the meta-analysis
Forest plots of random-effects meta-analysis (between-study variance estimator: DerSimonian and Laird (DL)) for cholesterol efflux capacity (CEC) differences between coronary artery disease (CAD) vs. non-CAD group. Shown is the standardized mean difference (SMD) together with its 95% confidence interval (95% CI) as effect measure
Forest plots of random-effects meta-analysis (between-study variance estimator: DerSimonian and Laird (DL)) for the differences of coronary artery disease (CAD) risk between highest cholesterol efflux capacity (CEC) vs. lowest CEC groups. Shown is the odds ratio (OR)/ relative risks (RR)/hazard ratio (HR) together with their 95% confidence interval (95% CI) as effect measure
Dose-response analyses for cholesterol efflux capacity (CEC) and coronary artery disease (CAD) (A), and cardiovascular mortality (B). Shown is the odds ratio (OR) together with its 95% confidence interval (95% CI) as effect measure
Forest plots of random-effects meta-analysis (between-study variance estimator: DerSimonian and Laird (DL)) for the differences of cardiovascular mortality risk between highest cholesterol efflux capacity (CEC) vs. lowest CEC groups. Shown is the odds ratio (OR)/ hazard ratio (HR) together with their 95% confidence interval (95% CI) as effect measure
Background The preventive effect of cholesterol efflux capacity (CEC) on the progression of atherosclerotic lesions has been confirmed in animal models, but findings in the population are inconsistent. Therefore, this meta-analysis aimed to systematically investigate the relationship of CEC with coronary artery disease (CAD) and cardiovascular mortality in a general population. Methods Four electronic databases (PubMed, Embase database, Cochrane Library, Web of Science) were searched from inception to February 1st, 2022 for relevant studies, without any language restriction. For continuous variables, the mean and standard deviation (SD), maximum adjusted odds ratios (ORs), relative risks (RRs), or hazard ratios (HRs) and 95% confidence intervals (CIs) were extracted. The random-effects model was adopted to calculate the pooled results, and dose-response analyses were conducted. All pooled results were expressed by standardized mean difference (SMD) and ORs. Results Finally, 18 observational studies were included. Compared with the non-CAD group, the CAD group (SMD -0.48, 95% CI − 0.66 to − 0.30; I ² 88.9%) had significantly lower CEC. In the high-CEC population, the risks of CAD (OR 0.52, 95% CI 0.37 to 0.71; I ² 81%) significantly decreased, and a linear negative dose-response was detected. However, an association between CEC and the risk of cardiovascular mortality was not found (OR 0.44, 95% CI 0.18 to 1.06; I ² 83.2%). Conclusions This meta-analysis suggests that decreased CEC is strongly associated with the risk of CAD, independent of HDL-C level. However, a decreased CEC seems not to be related to cardiovascular mortality. Meanwhile, CEC is linearly negatively correlated with the risk of CAD.
Measurement of high-density lipoprotein (HDL) function in patients with severe AS. HDL particles were isolated by PEG from women (F, red, A) and men (M, blue, B) with severe AS. ApoA-I containing particles were probed with human anti-apoA-I antibody and revealed by chemiluminescence. Molecular size markers are shown. (C) ApoA-I preβ1-HDL and α-HDL particles were quantified by Western blotting followed by densitometric scanning. (D) ABCA1-mediated cholesterol efflux capacity to HDL from women (red) and men (blue) with severe AS. (E) Formation of lipidated apoA-I particles from BHK cells expressing ABCA1 and separation by 2D-PAGGE. (F) LCAT activity (%/h) in plasma samples. After lipid extraction, ³[H]-unesterified cholesterol and ³[H]-cholesteryl ester were separated by thin liquid chromatography and assayed for radioactivity
Characterization of human aortic vascular interstitial cells (HAVICs). (A, B) Marker for HAVICs in culture, alpha-smooth muscle actin (α-SMA), and ATP-Binding Cassette A1 (ABCA1) protein by immunofluorescence. Immunofluorescence staining with α-SMA (green) and ABCA1 (red) in (A) calcified and (B) non-calcified HAVICS are shown. Nuclei were stained (blue) with 4′,6-diamidino-2-phenylindole (DAPI). (C) ABCA1 protein expression in BHK cells was used as a control. Cells (100 μg) were separated by SDS-PAGE (8–28%) and probed for ABCA1 detection. (D) Data are expressed as the ratio of quantified band intensities for ABCA1 and GAPDH proteins
Cholesterol efflux to control HDL is reduced in calcified human aortic vascular interstitial cells (HAVICs) in a dose dependent manner. (A) After incubation, with ³[H]-cholesterol 2 μCi/mL for 24 h in DMEM 1% FBS HAVICs (calcified and non-calcified) were washed twice with PBS. Cells were incubated with increased doses of pooled control, high-density lipoprotein (HDL) from healthy individuals for 24 h. (Inset) Cellular cholesterol efflux at 5% plasma HDL. Characterization of cholesterol efflux from calcified HAVICs. Radiolabelled HAVICs, Calcified (B) vs. non-calcified (C), were incubated with 5% plasma control HDL for 8 h. Media from cells samples were collected, concentrated and separated by 2D-PAGGE, and apoA-I was detected by Western blotting. Molecular size markers are shown. HDL, high-density lipoprotein; HAVIC, human aortic interstitial cells
Background Calcification of the aortic valve is a common heart valve disorder, in some cases leading to clinically impactful severe aortic stenosis (AS). Sex-specific differences in aortic valve calcification (ACV) exist, with women having a lower burden of calcification than men as measured by computed tomography; however, the pathophysiological mechanism that leads to these differences remains unclear. Methods Using cultured human Tamm-Horsfall protein 1 (THP-1) macrophages and human aortic valve interstitial cells, the effects of high-density lipoprotein (HDL) particles isolated from the plasma of men and women with severe AS were studied for cholesterol efflux capacity (CEC). Results HDL-CEC was assessed in 46 patients with severe AS, n = 30 men, n = 16 women. ATP-Binding Cassette A1 (ABCA1)-mediated HDL-CEC was measured from human cultured THP-1 macrophages to plasma HDL samples. Women with severe AS had more ABCA1-mediated HDL-CEC, as compared to men (8.50 ± 3.90% cpm vs. 6.80 ± 1.50% cpm, P = 0.04). HDL pre-β1 and α-particles were higher in woman than in men by spectral density, (pre-β1 HDL, 20298.29 ± 1076.15 vs. 15,661.74 ± 789.00, P = 0.002, and α-HDL, 63006.35 ± 756.81 vs. 50,447.00 ± 546.52, P = 0.03). Lecithin-cholesterol acyltransferase conversion of free cholesterol into cholesteryl esters was higher in women than men (16.44 ± 9.11%/h vs. 12.00 ± 8.07%/h, P = 0.03). Conclusions Sex-specific changes in various parameters of HDL-CEC were found in patients with severe AS. Sex-based modifications in HDL functionality by HDL-CEC might account for the reduced burden of calcification in women vs. men with severe AS. Therefore, future studies should target sex-related pathways in AS to help to improve understanding and treatment of AS. Graphical abstract Sex specifc differences in AVC and differences associated with HDL function in men and women with severe AS. When compared to men, women had higher preβ-HDL and α-HDL migrating particles, higher cholesterol efflux to HDL, and higher lecithin cholesterol acyl transferase (LCAT) activity, possibly indicating that improved reverse cholesterol transport may be protective against worsened calcification.
Background Hepatocyte nuclear factor 4α (HNF4α) and glucocorticoid receptor (GR), master regulators of liver metabolism, are down-regulated in fatty liver diseases. The present study aimed to elucidate the role of down-regulation of HNF4α and GR in fatty liver and hyperlipidemia. Methods Adult mice with liver-specific heterozygote (HET) and knockout (KO) of HNF4α or GR were fed a high-fat-high-sugar diet (HFHS) for 15 days. Alterations in hepatic and circulating lipids were determined with analytical kits, and changes in hepatic mRNA and protein expression in these mice were quantified by real-time PCR and Western blotting. Serum and hepatic levels of bile acids were quantified by LC-MS/MS. The roles of HNF4α and GR in regulating hepatic gene expression were determined using luciferase reporter assays. Results Compared to HFHS-fed wildtype mice, HNF4α HET mice had down-regulation of lipid catabolic genes, induction of lipogenic genes, and increased hepatic and blood levels of lipids, whereas HNF4α KO mice had fatty liver but mild hypolipidemia, down-regulation of lipid-efflux genes, and induction of genes for uptake, synthesis, and storage of lipids. Serum levels of chenodeoxycholic acid and deoxycholic acid tended to be decreased in the HNF4α HET mice but dramatically increased in the HNF4α KO mice, which was associated with marked down-regulation of cytochrome P450 7a1, the rate-limiting enzyme for bile acid synthesis. Hepatic mRNA and protein expression of sterol-regulatory-element-binding protein-1 (SREBP-1), a master lipogenic regulator, was induced in HFHS-fed HNF4α HET mice. In reporter assays, HNF4α cooperated with the corepressor small heterodimer partner to potently inhibit the transactivation of mouse and human SREBP-1C promoter by liver X receptor. Hepatic nuclear GR proteins tended to be decreased in the HNF4α KO mice. HFHS-fed mice with liver-specific KO of GR had increased hepatic lipids and induction of SREBP-1C and PPARγ, which was associated with a marked decrease in hepatic levels of HNF4α proteins in these mice. In reporter assays, GR and HNF4α synergistically/additively induced lipid catabolic genes. Conclusions induction of lipid catabolic genes and suppression of lipogenic genes by HNF4α and GR may mediate the early resistance to HFHS-induced fatty liver and hyperlipidemia. Graphical abstract
Distribution of visceral adipose tissue (VAT) mass in subjects with different grading of hepatic steatosis
a Correlation between DXA–VAT mass and predicted VAT by Model 1. b Bland–Altman plots for DXA–VAT mass and predicted VAT by Model 1 with 95% limits of agreement. The middle line indicates the mean difference between DXA measured VAT and predicted VAT. The red dotted lines represent the limits of agreement (LoA)
a Correlation between DXA–VAT mass and predicted VAT by Model 2. b Bland–Altman plots for DXA–VAT mass and predicted VAT by Model 2 with 95% limits of agreement. The middle line indicates the mean difference between DXA measured VAT and predicted VAT. The red dotted lines represent limits of agreement (LoA)
Background Obesity, especially presenting with excessive amounts of visceral adipose tissue (VAT), is strongly associated with insulin resistance (IR), atherosclerosis, metabolic syndrome, and cardiovascular diseases (CVDs). Aims To construct a predication equation for estimating VAT mass using anthropometric parameters and validate the models with a validation group. Methods Five hundred fifteen subjects (366 for the derivation group and 149 for the validation group) were enrolled in the study. The anthropometric parameters, blood lipid profile, and VAT mass were accessed from medical records. Stepwise regression was applied to develop prediction models based on the dual X–ray absorptiometry (DXA)-measured VAT mass in the derivation group. Bland–Altman plots and correlation analysis were performed to validate the agreements in the validation group. The performance of the prediction equations was evaluated with the Hosmer–Lemeshow test and area under the curve (AUC). Results Model 1, which included age, sex, body mass index (BMI), triglyceride (TG), high-density lipoprotein (HDL), and the grade of hepatic steatosis, had a variance of 70%, and model 2, which included age, sex, weight, height, TG, HDL, and the grade of hepatic steatosis, had a variance of 74%. The VAT mass measured by DXA was correlated with age, sex, height, weight, BMI, TG, HDL, and grade of hepatic steatosis. In the validation group, the VAT mass calculated by the prediction equations was strongly correlated with the DXA–VAT mass ( r = 0.870, r = 0.875, respectively). The AUC, sensitivity, and specificity of the two prediction equations were not significantly different (both P = 0.933). Conclusion The study suggests that prediction equations including age, sex, height, BMI, weight, TG, HDL, and the grade of hepatic steatosis could be useful tools for predicting VAT mass when DXA is not available.
Flow diagram of subjects included in the cohort study
Kaplan-Meier analysis of future prediabetes risk according to LDL:HDL ratio quartiles. LDL:HDL ratio: low-density lipoprotein:high-density lipoprotein cholesterol ratio
Hazard ratios (95% confidence intervals) for the non-linear relationship between LDL:HDL ratio and the risk of prediabetes. LDL:HDL ratio: low-density lipoprotein:high-density lipoprotein cholesterol ratio
Background Low-density lipoprotein:high-density lipoprotein cholesterol ratio (LDL:HDL ratio) has a good performance in identifying diabetes mellitus (DM) and insulin resistance. However, it is not yet clear whether the LDL:HDL ratio is associated with a high-risk state of prediabetes. Methods This cohort study retrospectively analyzed the data of 100,309 Chinese adults with normoglycemia at baseline. The outcome event of interest was new-onset prediabetes. Using multivariate Cox regression and smoothing splines to assess the association of LDL:HDL ratio with prediabetes. Results During an average observation period of 37.4 months, 12,352 (12.31%) subjects were newly diagnosed with prediabetes. After adequate adjustment for important risk factors, the LDL:HDL ratio was positively correlated with the prediabetes risk, and the sensitivity analysis further suggested the robustness of the results. Additionally, in stratified analysis, we discovered significant interactions between LDL:HDL ratio and family history of DM, sex, body mass index and age (all P -interaction < 0.05); among them, the LDL:HDL ratio-related prediabetes risk decreased with the growth of body mass index and age, and increased significantly in women and people with a family history of DM. Conclusions The increased LDL:HDL ratio in the Chinese population indicates an increased risk of developing prediabetes, especially in women, those with a family history of DM, younger adults, and non-obese individuals.
Background Systemic factors can strongly affect how tumour cells behave, grow, and communicate with other cells in breast cancer. Lipid metabolic reprogramming is a systemic process that tumour cells undergo; however, the formation and dynamics of lipids associated with the tumour immune microenvironment (TIME) remain unclear. The investigation of the sophisticated bidirectional crosstalk of tumour cells with cancer metabolism, gene expression, and TIME could have the potential to identify novel biomarkers for diagnosis, prognosis, and immunotherapy. This study aimed to construct a prognostic signature to detect the bicrosstalk between the lipid metabolic system and the TIME of breast cancer. Methods To detect the expression of LRGs and execute GO/KEGG analysis, the R program was chosen. Considering the clinical information and pathological features, a prognostic gene signature was constructed by LASSO Cox regression analysis. TMB, MSI, and immune infiltration analyses were performed, and consensus cluster analysis of LRGs was also performed. Results These 16 lipid metabolism-related genes (LRGs) were mainly involved in the process of lipid metabolism and fatty acid binding in breast cancer. Prognosis analysis identified the prognostic value of FABP7(Fatty acid binding protein 7) and NDUFAB1(NADH:ubiquinone oxidoreductase subunit AB1) in breast cancer patients. The prognostic gene signature constructed with FABP7 and NDUFAB1 was significantly related to immune cell infiltration and could predict the overall survival rate with above average correctness of breast cancer patients. FABP7 and NDUFAB1 were proven to have relevance in immune cell infiltration and tumour mutation burden (TMB). Consensus cluster analysis identified that the upregulated mRNAs were mostly related to the oncogenesis process, while the downregulated mRNAs were associated with immune-related signalling pathways. Conclusion A comprehensive analysis was performed to evaluate the lipid metabolic system and identified a signature constructed by two prognostic genes for immunotherapies in breast cancer. The results also revealed evidence of vulnerabilities in the interplay between the lipid metabolic system and the TIME in breast cancer. Further data with clinical studies and experiments are warranted.
Background Monoacetyldiglycerides (MAcDG), are acetylated triglycerides (TG) and an emerging class of bioactive or functional lipid with promising nutritional, medical, and industrial applications. A major challenge exists when analyzing MAcDG from other subclasses of TG in biological matrices, limiting knowledge on their applications and metabolism. Methods Herein a multimodal analytical method for resolution, identification, and quantitation of MAcDG in biological samples was demonstrated based on thin layer chromatography-flame ionization detection complimentary with C30-reversed phase liquid chromatography-high resolution accurate mass tandem mass spectrometry. This method was then applied to determine the MAcDG molecular species composition and quantity in E. solidaginis larvae. The statistical method for analysis of TG subclass composition and molecular species composition of E. solidaginis larvae was one-way analysis of variance (ANOVA). Results The findings suggest that the proposed analytical method could simultaneously provide a fast, accurate, sensitive, high throughput analysis of MAcDG from other TG subclasses, including the fatty acids, isomers, and molecular species composition. Conclusion This method would allow for MAcDG to be included during routine lipidomics analysis of biological samples and will have broad interests and applications in the scientific community in areas such as nutrition, climate change, medicine and biofuel innovations. Graphical abstract
Development of RNA-based therapies for the treatment of cardiovascular and other disorders. AsO: antisense oligonucleotides; FDA: Food and Drug Administration; EMA: European Medicines Agency; CV: cardiovascular; HoFH: homozygous familial hypercholesterolemia; siRNA: small interfering ribonucleic acids; hATTR: hereditary transthyretin amyloidosis; Lp(a): lipoprotein(a)
Graphic depiction of antisense oligonucleotide and RNA interference mechanism of actions
This review focuses on antisense oligonucleotides and small interfering ribonucleic acid therapies approved or under development for the management of lipid disorders. Recent advances in RNA-based therapeutics allow tissue-specific targeting improving safety. Multiple potential target proteins have been identified and RNA-based therapeutics have the potential to significantly improve outcomes for patients with or at risk for atherosclerotic cardiovascular disease. The advantages of RNA-based lipid modifying therapies include the ability to reduce the concentration of almost any target protein highly selectively, allowing for more precise control of metabolic pathways than can often be achieved with small molecule-based drugs. RNA-based lipid modifying therapies also make it possible to reduce the expression of target proteins for which there are no small molecule inhibitors. RNA-based therapies can also reduce pill burden as their administration schedule typically varies from weekly to twice yearly injections. The safety profile of most current RNA-based lipid therapies is acceptable but adverse events associated with various therapies targeting lipid pathways have included injection site reactions, inflammatory reactions, hepatic steatosis and thrombocytopenia. While the body of evidence for these therapies is expanding, clinical experience with these therapies is currently limited in duration and the results of long-term studies are eagerly awaited.
Structure of sciadonic acid (SA). SA is a non-methylene interrupted fatty acid present in Delta-5 oil as a triacylglycerol, representing 20–25% of total fatty acids in the oil. It is a 20-carbon fatty acid, with 3 double bonds present in Δ-5, 11, and 14 positions in cis-configuration. As a result of having only 2 methylene-interrupted fatty acids, it has good oxidative stability like a dienoic fatty acid. In skin, sciadonic acid exerts anti-inflammatory properties by displacing arachidonic acid from lipid pools; but may also potentially form bioactive, aborted cyclooxygenase and lipoxygenase and other eicosanoid products (a very poorly studied area). In our example herein, the C13-hydrogen at the center of the 1,4 cis, cis pentadiene system is extracted, following oxygen attack at C-15, forming 15-hydroxy-5,11,13-eicosatrienoic acid by the cyclooxygenase system. Another cyclooxygenase product (not shown) is 11-hydroxy-5,12,14-eiosatrienoic acid [64]. If SA were acted on by a skin 12-lipoxygenase, then 12-hydroxy-5,10,14-eicosatrienoic acid would be theoretically formed (not shown). See the "Introduction" section for further discussion and references
Simplified Experimental Design. Shown are measurements and treatments applied to each subject’s forearm on days 0–28, in the order conducted (top of each box, down). Test site 1, Untreated control; Site 2, Untreated control, chemically damaged with 2% SLS; and Test Site 3, Delta-5 oil applied to SLS-damaged skin. TEWL (g/m²h) and NOVA Impedance (units are in arbitrary Dermal Phase Meter impedance units; DPMIU) were measured just before SLS was applied to the skin on Day 0 (baseline); and redness (measured by Visual Expert Grading Scores; VEGS) was measured just after SLS was applied to the skin on Day 0*. On Day 1, redness, TEWL and impedance values are measured 1 day after SLS injury, then Delta-5 oil is applied to the Delta-5 oil group, so that on Day 2, Delta-5 oil has been on the skin for 24 h. Redness was not measured on Day 2. D5 2X/d, Delta-5 oil applied twice per day (see text for further details)
a and b: TEWL (g/m²h) evaluated as differences from Day 1 in Delta-5 oil-SLS damaged and untreated damaged groups at various time points, with- (Fig. 3a) and without (Fig. 3b) control correction. Values represent the means of differences from each time point from day 1. Values from each time point were divided by the corresponding untreated control value in Fig. 3a. *p ≤ 0.05; **p ≤ 0.01. Percents displayed represent the percent differences between Delta-5 oil-SLS damaged and untreated damaged groups. Standard deviations are not shown for readability of the graphs; and can be found in Table 1
Impedance (Units are in arbitrary Dermal Phase Meter impedance units; DPMIU) evaluated as differences from Day 1 in Delta-5 oil- and untreated groups, shown as means at various time points. See Fig. 3 for statistical details and explanations. Standard deviations are not shown for readability of the graphs; and can be found in Table 1
Redness (Visual Expert Grading Scores; VEGS) evaluated in Delta-5 oil and untreated groups at various time points, shown as mean VEGS at each time point. Note that redness was not evaluated as differences from Day 1 for reasons explained in the text. Percents displayed represent percent differences for the means between Delta-5 oil-SLS damaged and untreated damaged groups at each time point. Standard deviations are not shown for readability of the graph but are found in the section “Results SLS study-Skin redness”. *p ≤ 0.05
Background Sciadonic acid (SA) is an anti-inflammatory fatty acid displacing arachidonic acid (ARA) from specific phospholipid pools, thus modulating downstream pro-inflammatory lipid mediators. Its novel anti-inflammatory actions have been studied in vitro, in pre-clinical models, and stemming from testimonials, after topical- and oral application. It has not been tested in a formal clinical study for topical benefits previously. Skin barrier layer was our focus as it has a critically important role in maintaining skin moisture balance. Methods Herein, forearm skin was left undamaged; or barrier layer was chemically-damaged with 2% sodium lauryl sulfate (SLS) for 24 h. SLS-damaged skin was left untreated or treated with Delta-5® oil containing 24% SA twice daily for 27 days. Barrier function was assessed by open chamber transepidermal water loss (TEWL) and skin surface impedance on days 0 (clear skin), -1 (1-day post-SLS), -2 (2-days post-SLS, 1-day post-Delta-5), -3, -7, and − 28. Results Relative to day 1, Delta-5 oil statistically significantly decreased TEWL vs. untreated damaged sites, on days 3 (125% more reduced), -7 (74% more reduced), and − 28 (69% more reduced). Decreases in TEWL following chemical damage indicates improved skin barrier repair and healing. Similar patterns were quantified for skin impedance. There was also reduced redness observed on days 3 and − 7 with Delta-5 oil vs. untreated SLS-damaged skin. Conclusions Delta-5 oil thus has anti-inflammatory potential in human skin, under controlled clinical conditions, to accelerate irritant-induced healing, and improve skin barrier function. Improvement in barrier function would benefit dermatitis, acne, eczema, and skin scarring. In normal skin, Delta-5 oil has potential to promote healthy, moisturized skin; and improve skin structure, elasticity, and firmness.
Objective Low-density lipoprotein cholesterol (LDL-C) is an important cardiovascular disease marker that is used to estimate the risk of acute coronary syndrome in patients. The Sampson equation is an accurate LDL-C equation, but its application in Chinese patients is unclear. Methods This study enrolled 12,989 consecutive Chinese patients with the acute coronary syndrome (ACS), LDL-C levels were determined by direct standard method and two indirect equations (Friedewald and Sampson). The detection accuracy and consistency of these two equations were compared in patients classified by triglyceride (TG). In addition, the efficiency of the Sampson equation was also evaluated in patients with different comorbidities. Results Patients were divided into six groups according to TG level, and indicated that the Sampson formula was more accurate than the Friedewald formula in all TG spectrums ( P < 0.001). The Friedewald formula may underestimate the risk in patients with TG > 400 mg/dL, especially in TG > 800 mg/dL group (r: 0.931 vs. 0.948, 0.666 vs. 0.898, respectively). Compared with the Friedewald equation, the Sampson equation showed more advantages in female, age ≥ 65, body index mass (BMI) < 25, non-smoker, and non-diabetes (0.954 vs. 0.937, 0.956 vs. 0.934, 0.951 vs. 0.939, 0.951 vs. 0.936, and 0.947 vs. 0.938, respectively) than those in male, age < 65, BMI ≥ 25, smoker, and diabetes. Conclusions Compared with the Friedewald equation, the Sampson equation is more accurate for LDL-C evaluation in Chinese patients diagnosed with ACS, especially in patients with hypertriglyceridemia even in those with TG > 800 mg/dL. Additionally, the Sampson equation demonstrates greater accuracy even in subgroups of various baseline characteristics and comorbidities.
Under physiological conditions, the lipid and protein levels in angptl3-knockout C57 mice were nearly normal. a, b, c: The levels of triglycerides, cholesterolemia and proteinuria were not different between the groups. (P > 0.05). d: Under a light microscope, there were no changes in the liver structure between wild-type and angptl3-/- mice. e, f: The glomerular structure of knockout mice was also normal by light and electron microscopy. WT: wild type mice, KO: Angptl3-/- mice. *: P<0.05, **: P<0.01; the P values were derived from independent-sample t tests
Knockout of the angptl3 gene did not affect the liver or kidney function of mice in the physiological state and played an important role in LPS-induced nephropathy. a, b, c: The levels of triglycerides, cholesterolemia and proteinuria in the three groups. d: Lipid droplet deposition in the liver tissue of each group of mice, with a magnification of 400X. e: Changes in the different groups, with a magnification of 5,000X. WT: wild-type mice, WL: wild-type mice stimulated with LPS, KL: Angptl3-/- mice stimulated with LPS. Each group included 5 mice. *: P<0.05, **: P<0.01; the P values were derived from one-way ANOVA
Angptl3-tg mice developed hyperlipidemia and varying degrees of proteinuria. a: Triglyceride levels in angptl3-tg mice were markedly increased at different time points. b: The cholesterol level in angptl3-tg mice was also significantly higher than that in wild-type mice at every time point. c: Changes in proteinuria levels in the three groups. d: Random EM images of the glomerular basement membrane surrounded by the epithelium and endothelium were taken at a magnification of 5,000X. WT: wild-type mice, WL: wild-type mice with LPS stimulation. Each group included 5 mice. *: P<0.05, **: P<0.01; the P values were derived from one-way ANOVA
The effects of ANGPTL3 on hepatocytes in the nephrotic state were observed in vitro. a: Oil Red O staining areas in the different groups, with a magnification of 400X. b: The OD data from Oil Red O staining. c: ELISA data showing LDL in the different groups. d: Changes in the triglyceride level in the different groups. WT: wild-type hepatocytes, miRNA: angptl3 gene-knockdown hepatocytes, miRNA+LPS: hepatocytes stimulated with LPS after angptl3 knockdown, Teg: hepatocytes transfected with angptl3. Each group included 5 mice. *: P <0.05, **: P <0.01; the P values were derived from one-way ANOVA
ANGPTL3 may affect the occurrence of PNS hyperlipidemia by impacting LPL expression in mouse liver tissue.: a, b, c: ANGPTL3 expression changes in wild-type or Angptl3-/- mice in the physiological and nephritis states. d The expression of LPL in wild-type or Angptl3-/- mice in the physiological and nephritis states. WT: wild-type mice, WL: wild-type mice stimulated with LPS, KO: Angptl3-/- mice, KL: Angptl3-/- mice stimulated with LPS. Each group included 5 mice. *: P<0.05, **: P<0.01; the P values were derived from one-way ANOVA
Background It is unclear why primary nephrotic syndrome (PNS) patients often have dyslipidemia. Recent studies have shown that angiopoietin-like protein 3 (ANGPTL3) is an important regulator of lipid metabolism. In this study, we explored how ANGPTL3 impacts dyslipidemia during PNS development. Methods We measured the serum levels of ANGPTL3 in PNS patients (n=196). Furthermore, the degree of proteinuria and lipid metabolism were examined in angptl3-overexpressing transgenic (angptl3-tg) mice at different ages. Moreover, in this study, we used the clustered regularly interspaced short palindromic repeats-associated protein 9 (CRISPR/Cas9) system to create angptl3-knockout (angptl3-/-) mice to investigate lipopolysaccharide (LPS)-induced nephrosis. Results Compared with that in the healthy group, the serum level of ANGPTL3 in the PNS group was significantly increased (32 (26.35-39.66) ng/ml vs. 70.44 (63.95-76.51) ng/ml, Z =-4.81, P < 0.001). There were significant correlations between the serum level of ANGPTL3 and the levels of cholesterol (r=0.34, P < 0.001), triglycerides (r= 0.25, P = 0.001) and low-density lipoprotein (r= 0.50, P < 0.001) in PNS patients. With increasing age, angptl3-tg mice exhibited increasingly severe hypertriglyceridemia and proteinuria. The pathological features of angptl3-tg mice included rich lipid droplet deposition in hepatocytes and diffuse podocyte effacement. Compared to wild-type mice, angptl3-/- mice showed significantly lower degrees of lipid dysfunction and proteinuria after stimulation with LPS. The effects of ANGPTL3 on nephrotic dyslipidemia were confirmed in cultured hepatocytes subjected to angptl3 knockdown or overexpression. Finally, significant alterations in lipoprotein lipase (LPL) levels were observed in liver tissues from Angptl3-/- and wild-type mice stimulated with LPS. Conclusions ANGPTL3 could be involved in the development of dyslipidemia, as well as proteinuria, during PNS pathogenesis. Inhibition of LPL expression may the mechanism by which ANGPTL3 induces hyperlipidemia in PNS.
The selection and analytic workflow of the study participants
Changes in lipid metabolism parameters between the 2 examination points in the HPP, HPE, and HPN groups. A. Bar plots comparing the change values (calculated as the difference between the 2 examinations) among the 3 groups. The error bar represents the standard deviation. B. Bar plots showing comparisons of adjusted post values among the 3 groups. The adjusted post value was presented as the estimated marginal means of the lipid metabolism parameters in the second examination adjusted for the first examination’s outcomes. The error bar represents the standard deviation. HPP, persistently positive H. pylori; HPE, H. pylori eradication; HPN, persistently negative H. pylori; HDL, high-density lipoprotein cholesterol; LDL, low-density lipoprotein cholesterol
Correlates of lipid metabolism change after H. pylori eradication. A. Heatmap showing the correlates of TG, HDL, and LDL changes after H. pylori eradication. The X-axis shows the 3 lipid metabolism parameters. The Y-axis lists 42 candidate predictors. Different color in each block demonstrates the corresponding P value of the comparisons between the increased and the decreased lipid metabolism patients for each candidate predictor by the independent t test. Smaller P values are presented by lighter color. P < 0.0012 (0.05/42) was determined significant after Bonferroni correction. B. Box plots comparing diastolic blood pressure after H. pylori eradication between the HDL-decreased and -increased groups. C. Box plots comparing mean platelet volume after H. pylori eradication between the HDL-decreased and -increased group. D. Box plots comparing of total protein after H. pylori eradication between the LDL-decreased and -increased group. The upper and lower whiskers on these boxes represent maximum and minimum values, respectively. Each box defines the first and third quartiles, while the marked center value within the box represents the median value. TG, triglycerides; LDL, low-density lipoprotein cholesterol; BMI, body mass index; HDL, high-density lipoprotein cholesterol; CG, calculus of gallbladder; FBG, fasting blood glucose; DBP, diastolic blood pressure; SBP, systolic blood pressure; WBC, white blood cells; NE, neutrophil count; NE%, neutrophil percentage; MO%, monocyte percentage; MO, monocyte count; LY%, lymphocyte percentage; LY, lymphocyte count; BASO%, basophil percentage; BASO, basophil count; EO%, eosinophil percentage; EO, eosinophil count; RBC, red blood cells; RDW, red blood cell volume distribution width; HCT, red blood cell volume; MCHC, mean corpuscular hemoglobin concentration; MCH, mean corpuscular hemoglobin; MCV, mean corpuscular volume; PLT, platelet count; Hb, hemoglobin; MPV, mean platelet volume; ALB, albumin; GLOB, globulin; A/G, albumin/globulin; TP, total protein; GT, γ-glutamate transpeptidase; AST, aspartate aminotransferase; ALT, alanine aminotransferase; AKP, alkaline phosphatase; Cre, creatinine; DBil, direct bilirubin; TBil, total bilirubin; UUA, urine uric acid; UPH, urine pH; BUN, blood urea nitrogen
Background The impact of Helicobacter pylori ( H. pylori ) eradication on metabolism of lipid and the potential predictor of such changes remain unclear. Methods This study retrospectively included subjects who underwent at least two ¹³ C urea breath tests between 2015 and 2019 at Wuhan Union Hospital. Based on two H. pylori ¹³ C examination results, subjects were divided into propensity score-matched persistently negative (HPN), persistently positive (HPP), and eradication (HPE) groups. The changes in lipid measurements from before to after H. pylori eradication, including high-density lipoprotein (HDL), low-density lipoprotein (LDL), total cholesterol, and triglycerides, were compared within and between groups. Forty-two candidate factors were tested for their ability to predict lipid metabolism changes after H. pylori eradication. Results After propensity score matching, 3412 matched cases were analyzed. Within-group comparisons showed significantly decreased HDL ( P < 0.001) and increased LDL ( P < 0.001) at the second examination in both the HPE and HPP groups. Between-group comparisons showed that the HDL decrease of the HPE group was significantly larger and smaller when compared with the HPN ( P = 0.001) and HPP ( P = 0.004) group, respectively. Uni- and multivariate analyses showed that low diastolic blood pressure (DBP) ( P = 0.002) and high mean platelet volume (MPV) ( P = 0.001) before eradication were associated with increased HDL after eradication. Low total protein (TP) ( P < 0.001) was associated with decreased LDL after eradication. Conclusions Compared with sustained H. pylori infectious states, H. pylori eradication alleviated the lipid metabolism deterioration but did not restore it to the uninfected level within 1.5 years after eradication. Patients with low DBP, high MPV, and low TP may reap a greater lipid-metabolism benefit from H. pylori eradication.
Flow chart of the research object
Multivariate analysis of the relationship between serum uric acid and dyslipidaemia and each component of dyslipidaemia, after adjusting for variable (except for the stratified variables) such as ethnicity, gender, area, age, educational level, occupation, smoking status, alcohol drinking status, tea, hypertension, diabetes, red meat, body mass index, physical activity, total energy intake, waist circumference, and hip circumference
The dose-response relationship between serum uric acid and dyslipidaemia and each component of dyslipidaemia, after adjusting for variables (except for the stratified variables) such as ethnicity, gender, area, age, educational level, occupation, smoking status, alcohol drinking status, tea, hypertension, diabetes, red meat, body mass index, physical activity, total energy intake, waist circumference, and hip circumference
Background The association between serum uric acid (SUA) and the components of dyslipidaemia and their dose-response relationships have not been thoroughly explored. This study assessed the relationship between SUA and each dyslipidaemia component in Dong, Miao, and Bouyei populations in Guizhou by sex and ethnicities and investigated the dose-response relationship. Methods In total, 16,092 participants aged 30–79 years from The China Multi-Ethnic Cohort (CMEC) Study were examined. Multivariable logistic regression models were applied to explore the relationship between SUA and each dyslipidaemia component by sex and three ethnicities. The dose-response associations between SUA and various dyslipidaemias were investigated using restricted cubic spline regression. Results After controlling for confounding factors, the SUA level in total participants positively correlated with each dyslipidaemia component, and women had higher odds ratios (ORs) for each dyslipidaemia component than men ( P for trend < 0.001). At the SUA level > 6.37 mg/dL, ORs (95% CI) for dyslipidaemia in the Dong, Miao and Bouyei were 2.89 (2.00–4.19), 2.43 (1.70–3.48), and 3.26 (2.23–4.78), respectively. When the SUA concentration increased by 1 mg/dL, the ORs (95% CI) for total dyslipidaemia was 1.31 (1.24–1.37). A positive dose-response but nonlinear association was found between SUA and total dyslipidaemia, high total cholesterol, and low HDL, whereas an inverse U-shaped association was found between SUA and high LDL-C ( P -nonlinear< 0.0001). Conclusion The SUA level was positively correlated with each dyslipidaemia component in Dong, Miao, and Bouyei adults, and sex and ethnic differences were also found. A nonlinear dose-response relationship was found between SUA levels and dyslipidaemia and its components. Further research is warranted to investigate the causal link between SUA levels and dyslipidaemia incidence.
Association between low total cholesterol, low HDL-cholesterol, low LDL-cholesterol and depression
Abstract Background Although high serum cholesterol is widely recognized as a major risk factor for heart disease, the health effects of low cholesterol are less clear. Several studies have found a correlation between low cholesterol and depression, but the results are inconsistent. Methods Data from the National Health and Nutrition Examination Survey (NHANES) 2005-2018 were utilized in this cross-sectional study. The analysis of the relationship between cholesterol and depression was performed at three levels: low total cholesterol, low high-density lipoprotein (HDL) cholesterol and low-density lipoprotein (LDL) cholesterol. The inclusion criteria were as follows: (1) people with low (
Background Recent findings show that extracellular vesicle constituents can exert short- and long-range biological effects on neighboring cells in the brain, opening an exciting avenue for investigation in the field of neurodegenerative diseases. Although it is well documented that extracellular vesicles contain many lipids and are enriched in sphingomyelin, cholesterol, phosphatidylserines and phosphatidylinositols, no reports have addressed the lipidomic profile of brain derived EVs in the context of Metachromatic Leukodystrophy, a lysosomal storage disease with established metabolic alterations in sulfatides. Methods In this study, we isolated and characterized the lipid content of brain-derived EVs using the arylsulfatase A knockout mouse as a model of the human condition. Results Our results suggest that biogenesis of brain-derived EVs is a tightly regulated process in terms of size and protein concentration during postnatal life. Our lipidomic analysis demonstrated that sulfatides and their precursors (ceramides) as well as other lipids including fatty acids are altered in an age-dependent manner in EVs isolated from the brain of the knockout mouse. Conclusions In addition to the possible involvement of EVs in the pathology of Metachromatic Leukodystrophy, our study underlines that measuring lipid signatures in EVs may be useful as biomarkers of disease, with potential application to other genetic lipidoses.
Flowchart of the patients included in the study. HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; TC: total cholesterol; TG: triglycerides
Prevalence of dyslipidemia in the population (A) and in different sex groups (B) and age groups (C). Prevalence of hypertriglyceridaemia in the population with dyslipidemia (D) and in different sex groups (E) and age groups (F). TG: triglycerides
Odds ratios (95% confidence intervals) of dyslipidemia (A) and hypertriglyceridaemia (B) across breakfast consumption frequency categories. Model 1: crude model. Model 2: adjusted for age and sex. Model 3: model 2 plus adjusted for BMI, hypertension, hyperuricaemia, and diabetes. Model 4: model 3 plus adjusted for smoking, alcohol consumption, education, marital status, long-term contact kitchen oil fumes, business dinner attendance, and daily sleep time. CI: confidence interval; HDL-C: high-density lipoprotein cholesterol; LDL-C: low-density lipoprotein cholesterol; OR: odds ratio; TC: total cholesterol; TG: triglycerides
Background Dyslipidemia is a significant contributor to cardiovascular and cerebrovascular diseases. Research on the relationship between breakfast consumption frequency and dyslipidemia in the working population is lacking. Therefore, we aimed to investigate this relationship based on a retrospective cohort study of a large working population in China. Methods This retrospective cohort study used data from the physical examinations and questionnaire survey of working participants at Nanfang Hospital from January 20, 2015 to October 16, 2020. Univariate and multivariate analyses were conducted to explore the relationship between breakfast consumption frequency and dyslipidemia in this working population ( n = 7644). Results The prevalence of dyslipidemia among the participants was 26.4%. The univariate logistic regression test showed that the breakfast consumption frequency was inversely correlated with dyslipidemia. After adjusting for multiple factors, such as sex, age, body mass index, hypertension, hyperuricaemia, diabetes, smoking status, alcohol consumption, education level, marital status, long-term exposure to kitchen oil fumes, attending business dinners, and sleep time, it was found that breakfast consumption remained inversely associated with dyslipidaemia. The odds ratio for daily breakfast consumption was 0.466 (95% confidence interval 0.283–0.770, P = 0.003). After adjusting for confounding factors, we found that the higher the frequency of breakfast consumption, the lower the odds ratios for hypertriglyceridaemia. Conclusions This study demonstrated that breakfast consumption frequency was inversely correlated with dyslipidemia. The higher the frequency of breakfast, the lower the risk of hypertriglyceridaemia. This study provides a basis on which dietary suggestions for the working population and lifestyle guidance for patients with a clinical need to prevent dyslipidemia can be made.
Omega 3 polyunsaturated fatty acids (n-3 PUFA) are known to have beneficial effects on cardiovascular and metabolic health. However, whether different sources of n-3 PUFA, for instance fatty fish vs vegetable oils, could elicit different effects on glucose and lipid metabolism, remains to be determined. Herein we examine recent findings showing that while a plant-based n-3 PUFA supplementation for six months can reduce fasting blood glucose, marine-based n-3 PUFA can instead reduce serum levels of triglycerides. We also discuss the potential molecular mechanisms that could underlie these different effects on the regulation of glycolipid metabolism.
The study population flowchart
Kaplan–Meier curves for all-cause (A) and cardiovascular mortality (B) according to MHR tertiles. MHR monocyte-to-high-density lipoprotein-cholesterol ratio
Restricted cubic spline curves of relations between MHR with all-cause (A) and cardiovascular mortality (B). Analysis was adjusted for age, gender, ethnicity, smoker, drinker, DM, hypertension, HF, CHD, stroke, cancer, BMI, hemoglobin, platelets, LDL-C, triglyceride, albumin, and eGFR. The solid and dashed lines symbolize the hazard ratios and corresponding 95% confidence intervals, respectively
Restricted cubic spline curves of relations between MHR and mortality in different sex groups. (A) Female: all-cause mortality; (B) Female: cardiovascular mortality; (C) Male: all-cause mortality; (D) Male: cardiovascular mortality. Analysis was adjusted for age, ethnicity, smoker, drinker, DM, hypertension, HF, CHD, stroke, cancer, BMI, hemoglobin, platelets, LDL-C, triglyceride, albumin, and eGFR. The solid and dashed lines symbolize the hazard ratios and corresponding 95% confidence intervals, respectively
Background: Elevated monocyte-to-high-density lipoprotein-cholesterol ratio (MHR) is relevant to higher all-cause and cardiovascular mortality in patients with coronary artery disease and other comorbidities. However, the predictive values of MHR for mortality in the general population have been underutilized. This study investigated the association of MHR with all-cause and cardiovascular mortality in the adult population of the United States. Methods: This study included 34,335 participants (≥20 years) from the National Health and Nutrition Examination Survey 1999-2014 that were grouped according to MHR tertiles. Kaplan-Meier plots and long-rank tests were employed to investigate differences in survival among the groups. Moreover, the relationship of MHR with all-cause and cardiovascular mortality was further explored using multivariate Cox regression and restricted cubic spline analysis. Results: During the average follow-up of 93.5 ± 56 months, 4310 (12.6%) participants died, with 754 (2.2%) deaths attributed to cardiovascular diseases. Kaplan-Meier analysis revealed statistically obvious differences in all-cause and cardiovascular mortality among the MHR tertiles (log-rank test: all P < 0.001). In multi-adjusted models, participants in the highest tertile of MHR had an increased risk of all-cause (hazard ratio [HR] = 1.19, 95% confidence interval [CI] 1.10-1.29) and cardiovascular mortality (HR = 1.44, 95% CI 1.17-1.77), compared to those in the lowest tertile. Furthermore, the restricted cubic spline curve indicated that MHR had a non-linear association with all-cause mortality (P < 0.001), and the inflection point of MHR was 0.006. Each 2-fold change in MHR exhibited a 32% decrease (HR = 0.68, 95%CI 0.58-0.82) and a 20% increase (HR = 1.20, 95%CI 1.13-1.27) in the risk of all-cause mortality on the left and right flanks of the inflection point, respectively. Additionally, the risk of cardiovascular mortality increased by 21% per 2-fold change in MHR (HR = 1.21, 95%CI 1.07-1.36) in a linear manner. Conclusions: MHR was significantly related to all-cause and cardiovascular mortality in the general population independent of established risk factors.
Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver disease worldwide. The fat mass and obesity–associated protein (FTO) has been shown to be involved in obesity; however, its role in NAFLD and the underlying molecular mechanisms remain largely unknown. Methods FTO expression was first examined in the livers of patients with NAFLD and animal and cellular models of NAFLD by real-time PCR and Western blotting. Next, its role in lipid accumulation in hepatocytes was assessed both in vitro and in vivo via gene overexpression and knockdown studies. Results FTO expression was obviously elevated in the livers of mice and humans with hepatic steatosis, probably due to its decreased ubiquitination. FTO overexpression in HepG2 cells induced triglyceride accumulation, whereas FTO knockdown exerted an opposing effect. Consistent with the findings of in vitro studies, adeno-associated viruses 8 (AAV8)-mediated FTO overexpression in the liver promoted hepatic steatosis in C57BL/6J mice. Mechanistically, FTO inhibited the mRNA of peroxisome proliferator-activated receptor α (PPARα) in hepatocytes. Activation of PPARα by its agonist GW7647 reversed lipid accumulation in hepatocytes induced by FTO overexpression. Conclusions Overall, FTO expression is increased in NAFLD, and it promotes hepatic steatosis by targeting PPARα.
Background Conflicting results on the prognostic value of the visceral adiposity index (VAI) in patients with metabolic-associated fatty liver disease (MAFLD) have been reported. This study aimed to assess the diagnostic value of the VAI in MAFLD patients. Methods The Cochrane Library, PubMed, Embase, and other databases were searched to collect all documents that met the inclusion criteria from the establishment of the database to September 2021. The methodological quality of the included studies was assessed using the Newcastle–Ottawa Scale. The heterogeneity among the studies was analysed by the Cochran Q test and I ² test, and the appropriate model was selected according to the heterogeneity results. The diagnostic efficacy of the VAI was evaluated by sensitivity, specificity, and area under the curve, and a Fagan diagram was generated to evaluate the diagnostic ability of the VAI. Results A total of 9 studies were included. The overall quality of the included studies was good. Meta-analysis showed that the combined sensitivity of the VAI for the diagnosis of MAFLD was 0.70 [95% CI (0.69–0.71)], the combined specificity was 0.67 [95% CI (0.67–0.68)], the combined positive likelihood ratio was 2.08 [95% CI (1.87–2.31)], the combined negative likelihood ratio was 0.39 [95% CI (0.34–0.44)], and the combined diagnostic odds ratio was 5.81 [95% CI (4.73–7.14)]. The corresponding area under the curve was 0.79 [95% CI (0.75–0.82)]. Meta-regression analysis showed that the diagnostic method was a potential source of heterogeneity ( P < 0.05). The Fagan diagram showed that the precision of MAFLD diagnosis was 70% when the pretest probability was set to 50% and then supplemented by the VAI. Conclusions The VAI is an independent predictor in the diagnosis of MAFLD and may be helpful in the detection of MAFLD. A VAI > 2.33 suggests that patients have a high probability of having MAFLD.
Pooled analysis of the multivariate logistic regression analysis in the multi-center cross-sectional study. a High-level vs Low-level model. b Per mmol/L increase model
Flow-chart of the study selection in the present meta-analysis
Background Gallstone disease (GSD) is a common and costly biliary disorder. Multiple studies have investigated the associations between blood lipid metabolism and GSD risk; however, the results are inconsistent. This research aimed to comprehensively evaluate the relationships among serum total cholesterol, low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and GSD risk. Methods Firstly, a multi-center cross-sectional study was carried out. Subjects who participated in the health examination in three hospitals between January 2015 and May 2020 were recruited. Multivariable logistic regression was used to investigate blood lipid metabolism associated with GSD risk. Then, a meta-analysis was performed to verify the associations further. Medline and Embase databases were systematically searched before June 10, 2021. The DerSimonian and Laird random-effect model was utilized when the heterogeneity was high; otherwise, fixed-effect model was adopted. Results There were 548,934 eligible participants included in the multi-center study, and 45,392 of them were diagnosed with GSD. The results demonstrated that total cholesterol and HDL cholesterol were negatively associated with GSD risk in both high vs. low model and per mmol/L increase model, while triglyceride was positively associated with GSD risk in the per unit increase model. In the meta-analysis, 104 studies with approximately 3 million participants were finally included. The results verified that HDL cholesterol [odds ratio (OR) = 0.636, P = 5.97 × 10 − 16 in high vs low model; OR = 0.974, P = 6.07 × 10 − 05 in per unit model] and triglyceride (OR = 1.192, P = 3.47 × 10 − 05 in high vs. low model; OR = 1.011, P = 5.12 × 10 − 05 in per unit model) were related to GSD risk in the two models. Conclusions The findings indicated that low HDL cholesterol levels and high triglyceride levels were risk factors for GSD. This study provides a basis for identifying the population at high risk for GSD and implementing tertiary prevention strategies for GSD, thus contributing to GSD prevention as well as disease burden relief.
PRISMA flow chart of the literature search process
Forest plots presenting the quantitative synthesis of circulating chemerin levels, comparing the following groups in the sum of the included studies: MAFLD patients and controls (A); NAFL patients and controls (B); NASH patients and controls (C); and NASH patients and NAFL patients (Meta-analysis)
Forest plots presenting the quantitative synthesis of circulating chemerin levels, comparing the following groups in the sum of the included studies: moderate to severe steatosis and mild steatosis (A); present liver fibrosis and absent liver fibrosis (B); present lobular inflammation and absent lobular inflammation (C); and present portal inflammation and absent portal inflammation (D)
Meta-regression analysis of the effect of mean age on patients with MAFLD and healthy controls
Sensitivity analysis of the summary SMD on the difference in circulating chemerin levels between MAFLD patients and controls
Background and objectives Chemerin is a brand-new adipokine that has been linked to both inflammation and metabolic dysfunction. Even though a rising number of studies have connected chemerin to metabolic-associated fatty liver disease (MAFLD), formerly referred to as non-alcoholic fatty liver disease (NAFLD), this association has been controversial. Methods A comprehensive literature search was undertaken up to February 1, 2022, in the PubMed, Embase, Web of Science, CNKI, WANFANG, and CBM library databases. Circulating chemerin levels were obtained and summarized using the standardized mean difference (SMD) and 95% confidence interval (CI). Subgroup and meta-regression analyses were conducted to examine the possibility of heterogeneity. Results A total of 17 studies involving 2580 participants (1584 MAFLD patients and 996 controls) evaluated circulating chemerin levels in patients with MAFLD. The present study showed that higher chemerin levels were found in patients with MAFLD (SMD: 1.32; 95% CI: 0.29, 2.35) and nonalcoholic fatty liver (NAFL) (SMD: 0.75; 95% CI: 0.01, 1.50) compared to controls. However, circulating chemerin levels did not differ significantly in the following comparisons: nonalcoholic steatohepatitis (NASH) patients and controls (SMD: 0.75; 95% CI: -0.52, 2.03); NASH patients and NAFL patients (SMD: 0.16; 95% CI: -0.39, 0.70); moderate to severe steatosis and mild steatosis (SMD: 0.55; 95% CI: -0.59, 1.69); present liver fibrosis and absent liver fibrosis (SMD: 0.66; 95% CI: -0.42, 1.74); present lobular inflammation and absent lobular inflammation (SMD: 0.45; 95% CI: -0.53, 1.42); and present portal inflammation and absent portal inflammation (SMD: 1.92; 95% CI: -0.85, 4.69). Conclusions Chemerin levels were considerably greater in patients with MAFLD than in controls, despite the fact that they were not significantly linked to different liver tissue lesions of MAFLD. In different subtypes of MAFLD, in comparison to healthy controls, the chemerin levels of NAFL patients were higher, whereas, there was no obvious difference in chemerin levels between NASH patients and controls. It is possible that chemerin will be used as a biomarker in the future to track the development and progression of MAFLD.
Background The relationship of consumption of dietary fat and fatty acids with esophageal squamous cell carcinoma (ESCC) risk remains unclear. This study aimed to explore the relationship of dietary fat and fatty acids intake with ESCC risk. Methods This case-control study included 879 incident cases and 892 community-based controls recruited from Southwest China. A food frequency questionnaire was adopted to collect information about dietary information, and intake of fat, saturated fatty acid (SFA), monounsaturated fatty acid (MUFA), polyunsaturated fatty acid (PUFA), and total fatty acid (TFA) was calculated. Odds ratios (ORs) with 95% confidence intervals (95% CIs) were estimated using the logistic regression model. Results When comparing the highest with lowest intake quintiles, MUFA (OR: 0.33, 95% CI: 0.21–0.51), PUFA (OR: 0.32, 95% CI: 0.20–0.51), and TFA (OR: 0.44, 95% CI: 0.28–0.70) were related to a reduced risk of ESCC after adjusting for confounders; for non-drinkers rather than drinkers, the intake of SFA was significantly related to a 61% (OR: 0.39, 95% CI: 0.19–0.81) reduced risk of ESCC when comparing the highest with the lowest intake quintiles. Dietary fat was not related to the risk of ESCC. Conclusions This study suggested that the more intake of MUFA and PUFA, the lower risk of ESCC, whereas the protective effect of TFA was only observed among non-drinkers. Strategic nutritional programs should consider food rich in unsaturated fatty acids to mitigate the occurrence of ESCC.
Levels of ceramides in (A) lean and obese groups and (B) obese-NDM and obese-DM groups
mRNA expression levels of major ceramide metabolizing enzymes in obese-NDM and obese-DM groups
Level of Cer and HOMA-IR in lean and obese groups and obese-NDM and obese-DM groups. A total ceramide (B) C16-ceramide (C) HOMA-IR. Correlation analysis of SPT mRNA expression with (D) total ceramide levels, (E) C16-ceramide and (F) HOMA-IR
Background Obesity and diabetes are two chronic metabolic diseases whose prevalence is increasing at an alarming rate globally. A close association between obesity, diabetes, and insulin resistance has been identified, and many studies have pinpointed obesity as a causal risk factor for insulin resistance. However, the mechanism underlying this association is not entirely understood. In the past decade, ceramides have gained attention due to their accumulation in certain tissues and their suggested role in initiating insulin resistance. This study aims to determine the association of specific ceramides and their major metabolizing enzymes with obesity-associated insulin resistance. Methods The samples comprised subcutaneous adipose tissues collected from three cohorts: lean non-diabetic (controls; n = 20), obese-non-diabetic ( n = 66), and obese-diabetic ( n = 32). Ceramide levels were quantified using LC-MS/MS and mRNA expression level for different enzymes were estimated using real-time PCR-based RNA expression analysis. Results C16-ceramide ( P = 0.023), C16-dihydro-ceramide ( P < 0.005), C18-dihydro-ceramide ( P = 0.009) and C24-ceramide ( P = 0.040) levels were significantly increased in the obese cohort compared to the control group. However, stratification of the obese group revealed a significant increase in the C16-ceramide levels ( P = 0.027) and mRNA over expression of the serine palmitoyl transferases enzyme subunit SPT1 ( P < 0.005) in the obese-diabetic cohort compared to the obese-non-diabetic cohort. Conclusions The present study indicates that C16-ceramide plays a pivotal role in inducing insulin resistance. Overexpression of SPT1 in the obese-diabetic group and its positive correlation with C16-ceramide suggest that C16-ceramide was generated through the de novo pathway.
Flow chart of the cohort
KIDMED score distribution in children aged 2- < 10 years (n = 28)
Background: Relatively little is known about the physiological whole blood fatty acid composition in young people. Likewise, few studies have addressed the question of correlations between Mediterranean diet (MedDiet) adherence and blood fatty acids in childhood. Methods: The fatty acid profile in whole blood from subjects, 46 days-19 years old (n = 152), without acute, chronic, or inflammatory diseases was analysed by gas chromatography. Dietary data was extracted from a 24-h recall in a subgroup of subjects (n = 60) into a modified Diet Quality Index for Children (KIDMED) questionnaire to evaluate MedDiet adherence. The cohort was divided into three age groups: < 2, 2- < 10, and 10-19 years. Kruskal-Wallis test and Bonferroni post hoc test were used to check for age group fatty acid differences. For correlations, Spearman's correlation coefficient and partial Spearman's correlation coefficient were used. Results: Linoleic acid, EPA, DHA, palmitic acid, and total saturated fatty acids were stable over age groups. Dihomo-gamma-linolenic acid (DGLA), arachidonic acid (AA), total polyunsaturated FAs (PUFA), and total omega-6 PUFA increased from age group < 2 years; alpha-linolenic acid, total omega-3 PUFA, oleic acid, and total monounsaturated FAs decreased. Adherence to the MedDiet was at low-medium level in 91.7% of the subjects. In the age group 2- < 10 yrs., the degree of adherence correlated positively with total MUFA and PUFA balance, negatively with total PUFA, total n6-PUFA, AA/DHA, AA/EPA, and n6/n3. Age did not influence the correlations as to PUFA balance and AA/EPA. Conclusions: Increased FA proportions with age were seen in the n6-series of PUFA. The n3-FA species decreased or were stable. The vast majority of the subjects with dietary data, 92%, obtained a KIDMED score indicative of low-medium adherence to the MedDiet. The score correlated negatively with various n6-species, i.e. the MedDiet suppressed circulating n6-PUFA. Whole blood may be used to investigate FAs and MedDiet adherence correlations which may be applied in the study of health issues in childhood.
Top-cited authors
Undurti Das
  • UND Life Sciences
Teruyoshi Yanagita
  • Saga University
Lila M Oyama
  • Universidade Federal de São Paulo
Demosthenes Panagiotakos
  • Harokopio University
Fabio Santos Lira
  • São Paulo State University