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ABCA1 and metabolic syndrome; a review of the ABCA1 role in HDL-VLDL production, insulin-glucose homeostasis, inflammation and obesity.
Babashamsi, MM, Koukhaloo, SZ, Halalkhor, S, Salimi, A, Babashamsi, M
Diabetes & metabolic syndrome. 2019;(2):1529-1534
Abstract
ATP-binding cassette transporter A1 (ABCA1) is an integral cell-membrane protein that mediates the rate-limiting step of high density lipoprotein (HDL) biogenesis and suppression of inflammation by triggering a number of signaling pathways via interacting with an apolipoprotein acceptor. The hepatic ABCA1 is involved in regulation of very low density lipoprotein (VLDL) production by affecting the apolipoprotein B trafficking and lipidation of VLDL particles. This protein is involved in protecting the function of pancreatic β-cells and insulin secretion by cholesterol homeostasis. Adipose tissue lipolysis is associated with ABCA1 activity. This transporter is involved in controlling obesity and insulin sensitivity by regulating triglyceride (TG) lipolysis and influencing on adiponectin, visfatin, leptin, and GLUT4 genes expression. The ABCA1 of skeletal muscle cells play a role in increasing the glucose uptake by enhancing the Akt phosphorylation and transferring GLUT4 to the plasma membrane. Abnormal status of ABCA1-regulated phenotypes is observed in metabolic syndrome. This syndrome is associated with the occurrence of many diseases. This review is a summary of the role of ABCA1 in HDL and VLDL production, homeostasis of insulin and glucose, suppression of inflammation and obesity controlling to provide a better insight into the association of this protein with metabolic syndrome.
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Effects of Freeze-Dried Grape Powder on High-Density Lipoprotein Function in Adults with Metabolic Syndrome: A Randomized Controlled Pilot Study.
Millar, CL, Duclos, Q, Garcia, C, Norris, GH, Lemos, BS, DiMarco, DM, Fernandez, ML, Blesso, CN
Metabolic syndrome and related disorders. 2018;(9):464-469
Abstract
BACKGROUND High-density lipoprotein (HDL) particles are protective against atherosclerosis. However, HDL function is impaired in metabolic syndrome (MetS) due to low-grade inflammation and dyslipidemia. Foods containing polyphenols, such as grapes, may prevent HDL dysfunction via antioxidant or anti-inflammatory effects. We evaluated the effects of grape powder ingestion on measures of HDL function in adults with MetS. METHODS Twenty adults (age: 32-70 years; body mass index: 25.3-45.4 kg/m2) consumed either 60 grams/day of freeze-dried grape powder (GRAPE) or a placebo for 4 weeks, separated by a 3-week washout period, in a randomized, double-blind crossover study. The primary outcome was serum paraoxonase-1 (PON1) arylesterase activity, a measure of HDL antioxidant function. Secondary outcomes included PON1 lactonase activity, plasma lipids, metabolic markers, cholesterol efflux capacity, and other HDL functional markers. RESULTS After 4 weeks, GRAPE did not alter the serum PON1 activity or other markers of HDL function compared with placebo. Measures of HDL function were positively correlated with each other and inversely with measures of insulin resistance and inflammation. GRAPE intake led to a significant reduction in fasting plasma triglycerides compared with placebo (P = 0.032). No other significant effects of GRAPE were observed for other plasma lipids, anthropometrics, or metabolic measures. CONCLUSIONS Grape powder consumption did not impact HDL function in this cohort of adults with MetS. However, it was shown to improve fasting triglycerides, a risk factor for cardiovascular disease.
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Weight Loss and Exercise Alter the High-Density Lipoprotein Lipidome and Improve High-Density Lipoprotein Functionality in Metabolic Syndrome.
Khan, AA, Mundra, PA, Straznicky, NE, Nestel, PJ, Wong, G, Tan, R, Huynh, K, Ng, TW, Mellett, NA, Weir, JM, et al
Arteriosclerosis, thrombosis, and vascular biology. 2018;(2):438-447
Abstract
OBJECTIVE High-density lipoprotein (HDL) lipid composition and function may better reflect cardiovascular risk than HDL cholesterol concentration. This study characterized the relationships between HDL composition, metabolism, and function in metabolic syndrome (MetS) patients and how changes in composition after weight loss (WL) and exercise treatments are related to function. APPROACH AND RESULTS Plasma samples from MetS patients (n=95) and healthy individuals (n=40) were used in this study. Subsets of the MetS group underwent 12 weeks of no treatment (n=17), WL (n=19), or WL plus exercise (WLEX; n=17). HDL was isolated using density-gradient ultracentrifugation. The HDL lipidome was analyzed by mass spectrometry, and particle size determined by nuclear magnetic resonance. Cholesteryl ester transfer protein activity and ex vivo HDL cholesterol efflux capacity (CEC) were assessed. The HDL lipidome in the MetS patients was substantially different from that in healthy individuals, mean particle size was smaller, and CEC was lower. Several HDL phospholipid and sphingolipid species were associated with HDL diameter and CEC. The HDL lipidome and particle size were modified toward the healthy individuals after WL and WLEX treatments, with greater effects observed in the latter group. Cholesteryl ester transfer protein activity was reduced after WL and WLEX, and CEC was improved after WLEX. CONCLUSIONS WLEX treatment in MetS patients normalizes the HDL lipidome and particle size profile and enhances CEC. HDL lipids associated with diminished CEC may represent novel biomarkers for early prediction of HDL dysfunction and disease risk and may represent potential therapeutic targets for future HDL therapies. CLINICAL TRIAL REGISTRATION URL: http://www.clinicaltrials.gov. Unique identifier: NCT00163943.
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High-Density Lipoprotein Reduction Differentially Modulates to Classical and Nonclassical Monocyte Subpopulations in Metabolic Syndrome Patients and in LPS-Stimulated Primary Human Monocytes In Vitro.
Grün, JL, Manjarrez-Reyna, AN, Gómez-Arauz, AY, Leon-Cabrera, S, Rückert, F, Fragoso, JM, Bueno-Hernández, N, Islas-Andrade, S, Meléndez-Mier, G, Escobedo, G
Journal of immunology research. 2018;:2737040
Abstract
The effect of metabolic syndrome on human monocyte subpopulations has not yet been studied. Our main goal was to examine monocyte subpopulations in metabolic syndrome patients, while also identifying the risk factors that could directly influence these cells. Eighty-six subjects were divided into metabolic syndrome patients and controls. Monocyte subpopulations were quantified by flow cytometry, and interleukin- (IL-) 1β secretion levels were measured by ELISA. Primary human monocytes were cultured in low or elevated concentrations of high-density lipoprotein (HDL) and stimulated with lipopolysaccharide (LPS). The nonclassical monocyte (NCM) percentage was significantly increased in metabolic syndrome patients as compared to controls, whereas classical monocytes (CM) were reduced. Among all metabolic syndrome risk factors, HDL reduction exhibited the most important correlation with monocyte subpopulations and then was studied in vitro. Low HDL concentration reduced the CM percentage, whereas it increased the NCM percentage and IL-1β secretion in LPS-treated monocytes. The LPS effect was abolished when monocytes were cultured in elevated HDL concentrations. Concurring with in vitro results, IL-1β serum values significantly increased in metabolic syndrome patients with low HDL levels as compared to metabolic syndrome patients without HDL reduction. Our data demonstrate that HDL directly modulates monocyte subpopulations in metabolic syndrome.