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      Bariatric Surgery Improves HDL Function Examined by ApoA1 Exchange Rate and Cholesterol Efflux Capacity in Patients with Obesity and Type 2 Diabetes

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          Abstract

          Bariatric surgery improves glycemic control better than medical therapy; however, the effect of bariatric surgery on HDL function is not well characterized. Serum samples were available at baseline, 1-, and 5-years post procedures, for 90 patients with obesity and type 2 diabetes who were randomized to intensive medical therapy ( n = 20), Roux-en-Y gastric bypass (RYGB, n = 37), or sleeve gastrectomy (SG, n = 33) as part of the STAMPEDE clinical trial. We examined serum HDL function by two independent assays, apolipoprotein A-1 exchange rate (AER) and cholesterol efflux capacity (CEC). Compared with baseline, AER was significantly higher at 5 years for participants in all treatment groups, but only increased significantly at 1 year in the RYGB and SG groups. CEC was divided into ABCA1-dependent and independent fractions, and the later was correlated with AER. ABCA1-independent CEC increased significantly only at 5 years in both surgical groups, but did not significantly change in the medical therapy group. There was no significant change in ABCA1-dependent CEC in any group. The increase in AER, but not ABCA1-independent CEC, was correlated with the reduction in body mass index and glycated hemoglobin levels among all subjects at 5 years, indicating that AER as a measure of HDL function would be a better reflection of therapy versus CEC.

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          Most cited references18

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          The ability to promote efflux via ABCA1 determines the capacity of serum specimens with similar high-density lipoprotein cholesterol to remove cholesterol from macrophages.

          We measured efflux from macrophages to apolipoprotein B-depleted serum from 263 specimens and found instances in which serum having similar high-density lipoprotein cholesterol (HDL-C) differed in their efflux capacity. Thus, we wanted to elucidate why efflux capacity could be independent of total HDL-C or apolipoprotein A-I (apoA-I). To understand why sera with similar HDL-C or apoA-I could differ in total efflux capacity, we assessed their ability to promote efflux via the pathways expressed in cAMP-treated J774 macrophages. Briefly, macrophages were preincubated with probucol to block ABCA1, with BLT-1 to block SR-BI, and with both inhibitors to measure residual efflux. ABCG1 efflux was measured with transfected BHK-1 cells. We used apolipoprotein B-depleted serum from specimens with similar HDL-C values at the 25(th) and 75(th) percentiles. Specimens in each group were classified as having high or low efflux based on total efflux being above or below the group average. We found that independently of HDL-C, sera with higher efflux capacity had a significant increase in ABCA1-mediated efflux, which was significantly correlated to the concentration of pre beta-1 HDL. The same result was obtained when these sera were similarly analyzed based on similar apoA-I. Sera with similar HDL-C or apoA-I differ in their ability to promote macrophage efflux because of differences in the concentration of pre beta-1 HDL.
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            High-density lipoprotein cholesterol as a predictor of coronary heart disease risk. The PROCAM experience and pathophysiological implications for reverse cholesterol transport.

            The incidence of coronary heart disease (CHD) was assessed via the Prospective Cardiovascular Münster (PROCAM) study in 19,698 volunteer subjects aged between 16 and 65 years. An adequate incidence of atherosclerotic CHD was only found in male subjects greater than 40 years of age. The analysis and subsequent 6 year follow-up period was, therefore, confined to 4559 male participants aged 40-64 years. In the follow-up period, 186 study participants developed atherosclerotic CHD (134 definite non-fatal myocardial infarctions (MIs) and 52 definite atherosclerotic CHD deaths including 21 sudden cardiac deaths and 31 fatal MIs). Univariate analysis revealed a significant association between the incidence of atherosclerotic CHD and high-density lipoprotein cholesterol (P < 0.001), which remained after adjustment for other risk factors.
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              All bariatric surgeries are not created equal: insights from mechanistic comparisons.

              Despite considerable scientific progress on the biological systems that regulate energy balance, we have made precious little headway in providing new treatments to curb the obesity epidemic. Diet and exercise are the most popular treatment options for obesity, but rarely are they sufficient to produce long-term weight loss. Bariatric surgery, on the other hand, results in dramatic, sustained weight loss and for this reason has gained increasing popularity as a treatment modality for obesity. At least some surgical approaches also reduce obesity-related comorbidities including type 2 diabetes and hyperlipidemia. This success puts a premium on understanding how these surgeries exert their effects. This review focuses on the growing human and animal model literature addressing the underlying mechanisms. We compare three common procedures: Roux-en-Y Gastric Bypass (RYGB), vertical sleeve gastrectomy (VSG), and adjustable gastric banding (AGB). Although many would group together VSG and AGB as restrictive procedures of the stomach, VSG is more like RYGB than AGB in its effects on a host of endpoints including intake, food choice, glucose regulation, lipids and gut hormone secretion. Our strong belief is that to advance our understanding of these procedures, it is necessary to group bariatric procedures not on the basis of surgical similarity but rather on how they affect key physiological variables. This will allow for greater mechanistic insight into how bariatric surgery works, making it possible to help patients better choose the best possible procedure and to develop new therapeutic strategies that can help a larger portion of the obese population.
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                Author and article information

                Journal
                Biomolecules
                Biomolecules
                biomolecules
                Biomolecules
                MDPI
                2218-273X
                04 April 2020
                April 2020
                : 10
                : 4
                : 551
                Affiliations
                [1 ]Department of Cardiovascular and Metabolic Sciences, Cleveland Clinic, Cleveland, OH 44195, USA; lorkows@ 123456ccf.org (S.W.L.); brubakg@ 123456ccf.org (G.B.)
                [2 ]Department of Quantitative Health Sciences, Cleveland Clinic, Cleveland, OH 44195, USA; rotrofd@ 123456ccf.org
                [3 ]Endocrinology Institute, Cleveland Clinic, Cleveland, OH 44195, USA; kashyas@ 123456ccf.org
                [4 ]Bariatric and Metabolic Institute, Department of General Surgery, Cleveland Clinic, Cleveland, OH 44195, USA; Philip.Schauer@ 123456pbrc.edu
                [5 ]Brigham and Women’s Hospital Heart and Vascular Center and Harvard Medical School, Boston, MA 02115, USA
                [6 ]Department of Cardiovascular Medicine, Cleveland Clinic, Cleveland, OH 44195, USA; nissens@ 123456ccf.org
                Author notes
                [* ]Correspondence: aminiaa@ 123456ccf.org (A.A.); smithj4@ 123456ccf.org (J.D.S.); Tel.: +1-216-444-6704 (A.A.); +1-216-444-2248 (J.D.S.)
                [†]

                Current address: Bariatric and Metabolic Institute, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, LA 70808, USA.

                Author information
                https://orcid.org/0000-0003-0553-3220
                https://orcid.org/0000-0002-1278-6245
                Article
                biomolecules-10-00551
                10.3390/biom10040551
                7226587
                32260470
                9da7d82e-4a92-487a-a851-041b28266b69
                © 2020 by the authors.

                Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

                History
                : 28 February 2020
                : 03 April 2020
                Categories
                Article

                bariatric surgery,hdl function,apoa1 exchange rate,cholesterol efflux capacity

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