Adiponectin increases macrophages cholesterol efflux and suppresses foam cell formation in patients with type 2 diabetes mellitus

2013 ◽  
Vol 229 (1) ◽  
pp. 62-70 ◽  
Author(s):  
Min Wang ◽  
Duan Wang ◽  
Yuhua Zhang ◽  
Xiaoming Wang ◽  
Yan Liu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cholesterol Efflux ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation

scholarly journals Antibodies Against the C-Terminus of ApoA-1 Are Inversely Associated with Cholesterol Efflux Capacity and HDL Metabolism in Subjects with and without Type 2 Diabetes Mellitus

2019 ◽  
Vol 20 (3) ◽  
pp. 732 ◽  
Author(s):  
Robin Dullaart ◽  
Sabrina Pagano ◽  
Frank Perton ◽  
Nicolas Vuilleumier
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Apolipoprotein B ◽  
Cholesterol Efflux ◽  
Hdl Cholesterol ◽  
Enzyme Linked Immunosorbent Assay ◽  
Cholesterol Efflux Capacity ◽  
C Terminus

Background: We determined relationships of cholesterol efflux capacity (CEC), plasma cholesterol esterification (EST) and cholesteryl ester transfer (CET) with anti-c-terminus apoA-1 (Ac-terAA1) and anti-apolipoprotein (apo)-1 (AAA1) autoantibodies in subjects with and without Type 2 diabetes mellitus (T2D). Methods: In 75 T2D subjects and 75 nondiabetic subjects, Ac-terAA1 and AAA1 plasma levels were measured by enzyme-linked immunosorbent assay. CEC was measured as [3H]-cholesterol efflux from human cultured fibroblasts to diluted individual subject plasma. Plasma EST and CET were assayed by isotope methods. Results: Ac-terAA1 and AAA1 levels and were similar between T2D and control subjects. Univariate regression analysis (n = 150) demonstrated that Ac-terAA1 levels were inversely correlated with CEC, EST, CET, total cholesterol, non-HDL cholesterol, triglycerides and apolipoprotein B, (p < 0.05 to p < 0.01), but not with glucose and HbA1c. In separate multivariable linear regression models, CEC, EST and CET were inversely associated with Ac-terAA1 levels independently of age, sex, T2D and drug use (β = −0.186, p = 0.026; β = −0.261, p < 0.001; and β = −0.321, p < 0.001; respectively). These associations were lost after additional adjustment for non-HDL cholesterol and triglycerides. No associations were observed for AAA1. Conclusions: CEC, plasma EST and CET are inversely associated with Ac-terAA1 autoantibodies, conceivably attributable to an inverse relationship of these autoantibodies with apolipoprotein B-containing lipoproteins.

Abstract 424: An IFNg-regulated Macrophage Protein Network Links Type 2 Diabetes to Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Catherine A Reardon ◽  
Amulya Lingaraju ◽  
Kelly Q Schoenfelt ◽  
Guolin Zhou ◽  
Ning-Chun Liu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Foam Cell ◽  
Cell Formation ◽  
Foam Cell Formation ◽  
Increased Risk ◽  
Macrophage Dysfunction ◽  
Macrophage Protein

Type 2 diabetics have a higher risk for atherosclerosis, but the mechanisms underlying the increased risk are poorly understood. Macrophages, which are activated in type 2 diabetes (T2D) and have a role in all stages of atherogenesis, are an attractive link. Our hypothesis is that T2D promotes macrophage dysfunction to promote atherosclerosis. To investigate the relationship between T2D and macrophage dysfunction, we used a proteomics approach to identify dysregulated proteins secreted from peritoneal macrophages in a diet induced mouse model of obesity and insulin resistance in the absence of hypercholesterolemia. Twenty-seven T2D responsive proteins were identified that predict defects in many of the critical functions of macrophages in atherosclerosis (e.g. decreased apoE- cholesterol efflux; decreased MFGE8 – efferocytosis, increased MMP12- matrix degradation). The macrophages from lean and obese mice were not lipid loaded, but the obese macrophages accumulated significantly more cholesterol when exposed to high levels of atherogenic lipoproteins in vitro suggesting that dysregulation of the T2D responsive proteins in diabetic mice render macrophages more susceptible to cholesterol loading. Importantly, many of these same protein changes, which were present in atherosclerotic Ldlr-/- mice with T2D, were normalized when these mice were fed non-diabetogenic hypercholesterolemic diets. Thus, foam cell formation in the presence and absence of T2D produces distinct effects on macrophage protein levels, and hence function. Further, we identify IFNγ as a mediator of the T2D responsive protein dysfunction. IFNγ, but not other cytokines, insulin or glucose, promote the T2D responsive protein dysregulation and increased susceptibility to cholesterol accumulation in vitro and the dysregulation is not observed in macrophage foam cells obtained from obese, diabetic IFNγ receptor 1 knockout animals. We also demonstrate that IFNγ can target these proteins in arterial wall macrophages in vivo . These studies suggest that IFNγ is an important mediator of macrophage dysfunction in T2D that may contribute to the enhanced cardiovascular risk in these patients.

scholarly journals Relationship of para- and perirenal fat and high-density lipoprotein and its function in patients with type 2 diabetes mellitus

2020 ◽  
Author(s):  
Jing Ke ◽  
Yan Wang ◽  
Simo Liu ◽  
Kun Li ◽  
YueChao Xu ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cholesterol Efflux ◽  
Density Lipoprotein ◽  
Cholesterol Efflux Capacity ◽  
Fat Thickness ◽  
The Relationship ◽  
Perirenal Fat

Abstract Background Para- and perirenal fat is a fat pad surrounding the kidneys. Recent researches have showed the association between para- and perirenal fat and cardiovascular diseases including atherosclerosis, hypertension and so on. Limited studies have explored the relation between para- and perirenal fat and serum high density lipoprotein (HDL) level, but the results were inconsistent. We aimed to assess the relationship between para-perirenal ultrasonographic fat thickness and serum HDL level and cholesterol efflux capacity of HDL in patients with type 2 diabetes mellitus (T2DM). Methods We recruited 58 subjects with T2DM and collected anthropometric indices including height, weight, waist circumference and so on. Para-perirenal ultrasonographic fat thickness (PUFT) was measured via ultrasound. Serum lipid profile and other metabolic indices were determined as well. Then we analyzed the relationship between PUFT and HDL level and cholesterol efflux capacity in all patients and subgroups divided by gender and body mass index (BMI). Results Patients with higher PUFT have lower serum HDL level but increased cholesterol efflux capacity of HDL. Further analysis showed that PUFT negatively correlated with serum HDL level in all patients, with no difference in group divided by BMI. While subgroup analysis divided by gender indicated that the relationship only existed in males. In addition, PUFT was positively correlated with cholesterol efflux capacity in all patients. However, subgroup analysis showed that PUFT did not significantly correlated with cholesterol efflux capacity in males and BMI ≥28kg/m 2 . Multiple stepwise regression analysis showed an independent association of PUFT and serum HDL level and cholesterol efflux capacity. Conclusions PUFT is closely correlated with serum HDL level and cholesterol efflux capacity in patients with T2DM.

scholarly journals Effect of Rosuvastatin on Cholesterol Efflux Capacity and Endothelial Function in Type 2 Diabetes Mellitus and Dyslipidemia

2018 ◽  
Vol 82 (5) ◽  
pp. 1387-1395 ◽  
Author(s):  
Kyong Yeun Jung ◽  
Kyoung Min Kim ◽  
Sun Kyoung Han ◽  
Han Mi Yun ◽  
Tae Jung Oh ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Function ◽  
Cholesterol Efflux ◽  
Cholesterol Efflux Capacity

scholarly journals Diabetes Impairs Cellular Cholesterol Efflux From ABCA1 to Small HDL Particles

2020 ◽  
Vol 127 (9) ◽  
pp. 1198-1210 ◽  
Author(s):  
Yi He ◽  
Graziella E. Ronsein ◽  
Chongren Tang ◽  
Gail P. Jarvik ◽  
W. Sean Davidson ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Cholesterol Efflux ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Cellular Cholesterol ◽  
Atp Binding Cassette Transporter ◽  
Cellular Cholesterol Efflux

Rationale: HDL (high-density lipoprotein) may be cardioprotective because it accepts cholesterol from macrophages via the cholesterol transport proteins ABCA1 (ATP-binding cassette transporter A1) and ABCG1 (ATP-binding cassette transporter G1). The ABCA1-specific cellular cholesterol efflux capacity (ABCA1 CEC) of HDL strongly and negatively associates with cardiovascular disease risk, but how diabetes mellitus impacts that step is unclear. Objective: To test the hypothesis that HDL’s cholesterol efflux capacity is impaired in subjects with type 2 diabetes mellitus. Methods and Results: We performed a case-control study with 19 subjects with type 2 diabetes mellitus and 20 control subjects. Three sizes of HDL particles, small HDL, medium HDL, and large HDL, were isolated by high-resolution size exclusion chromatography from study subjects. Then we assessed the ABCA1 CEC of equimolar concentrations of particles. Small HDL accounted for almost all of ABCA1 CEC activity of HDL. ABCA1 CEC―but not ABCG1 CEC―of small HDL was lower in the subjects with type 2 diabetes mellitus than the control subjects. Isotope dilution tandem mass spectrometry demonstrated that the concentration of SERPINA1 (serpin family A member 1) in small HDL was also lower in subjects with diabetes mellitus. Enriching small HDL with SERPINA1 enhanced ABCA1 CEC. Structural analysis of SERPINA1 identified 3 amphipathic α-helices clustered in the N-terminal domain of the protein; biochemical analyses demonstrated that SERPINA1 binds phospholipid vesicles. Conclusions: The ABCA1 CEC of small HDL is selectively impaired in type 2 diabetes mellitus, likely because of lower levels of SERPINA1. SERPINA1 contains a cluster of amphipathic α-helices that enable apolipoproteins to bind phospholipid and promote ABCA1 activity. Thus, impaired ABCA1 activity of small HDL particles deficient in SERPINA1 could increase cardiovascular disease risk in subjects with diabetes mellitus.

Sign in / Sign up

Export Citation Format

Share Document