ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity

Haan, Willeke de; Bhattacharjee, Ananya; Ruddle, Piers; Kang, Martin H.; Hayden, Michael R.

doi:10.1194/jlr.m045294

Cited by 78 publications

(59 citation statements)

References 35 publications

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“…Thus, negatively regulating the expression of the adiponectin gene leads to low plasma concentrations of adiponectin and so susceptibility to T2DM and obesity (Suriyaprom et al, 2014). In addition, numerous studies reported the association of the minor allele G of rs266729 with low plasma adiponectin concentrations (Jiala et al, 2014;de Haan et al, 2014). Unfortunately adiponectin plasma levels could not be determined in the current study due to logistic difficulties.…”

Section: Discussionmentioning

confidence: 60%

Association of adiponectin gene polymorphism rs266729 with type two diabetes mellitus in Iraqi population. A pilot study

Kaftan

Hussain

2015

Gene

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Section: Discussionmentioning

confidence: 60%

Association of adiponectin gene polymorphism rs266729 with type two diabetes mellitus in Iraqi population. A pilot study

Kaftan

Hussain

2015

Gene

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“…The expression of some other genes, including Fas or C/ebpb, which also are known to participate in adipocyte differentiation, remained unaffected. Notably, expression of Abca1 in adipocytes was recently reported to influence adipocyte lipid homeostasis (19). This observation may be important because Abcg1 deficiency in mouse macrophages was proposed to be compensated by an increase in Abca1 expression (20).…”

Section: Impaired Maturation In Stable Abcg1 Kd 3t3-l1 Adipocytesmentioning

confidence: 98%

Adipocyte ATP-Binding Cassette G1 Promotes Triglyceride Storage, Fat Mass Growth, and Human Obesity

et al. 2014

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The role of the ATP-binding cassette G1 (ABCG1) transporter in human pathophysiology is still largely unknown. Indeed, beyond its role in mediating free cholesterol efflux to HDL, the ABCG1 transporter equally promotes lipid accumulation in a triglyceride (TG)-rich environment through regulation of the bioavailability of lipoprotein lipase (LPL). Because both ABCG1 and LPL are expressed in adipose tissue, we hypothesized that ABCG1 is implicated in adipocyte TG storage and therefore could be a major actor in adipose tissue fat accumulation. Silencing of Abcg1 expression by RNA interference in 3T3-L1 preadipocytes compromised LPL-dependent TG accumulation during the initial phase of differentiation. Generation of stable Abcg1 knockdown 3T3-L1 adipocytes revealed that Abcg1 deficiency reduces TG storage and diminishes lipid droplet size through inhibition of Pparγ expression. Strikingly, local inhibition of adipocyte Abcg1 in adipose tissue from mice fed a high-fat diet led to a rapid decrease of adiposity and weight gain. Analysis of two frequent ABCG1 single nucleotide polymorphisms (rs1893590 [A/C] and rs1378577 [T/G]) in morbidly obese individuals indicated that elevated ABCG1 expression in adipose tissue was associated with increased PPARγ expression and adiposity concomitant to increased fat mass and BMI (haplotype AT>GC). The critical role of ABCG1 in obesity was further confirmed in independent populations of severe obese and diabetic obese individuals. This study identifies for the first time a major role of adipocyte ABCG1 in adiposity and fat mass growth and suggests that adipose ABCG1 might represent a potential therapeutic target in obesity.

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“…Blood was drawn at the indicated time points and was assayed for glucose, insulin, or C-peptide (17). Islets were isolated after perfusing the pancreas with collagenase (Sigma).…”

Section: Plasma Analysismentioning

confidence: 99%

“…HDL-cholesterol was measured after precipitation of the lipoproteins containing apolipoprotein B with heparin and manganese chloride (17).…”

Section: Plasma Analysismentioning

confidence: 99%

Hepatic ABCA1 Expression Improves β-Cell Function and Glucose Tolerance

et al. 2014

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Low HDL is a risk factor for the development of type 2 diabetes. Hepatic ABCA1 is the rate-limiting protein in HDL biogenesis, and mice lacking hepatic ABCA1 (ABCA1 -l/-l ) have very low plasma HDL concentrations. To investigate the role of hepatic ABCA1 in glucose tolerance and b-cell function, we used ABCA1 -l/-l mice, which showed impaired glucose tolerance without changes in insulin sensitivity. Insulin secretion was reduced following glucose gavage. Ex vivo, glucose stimulated insulin secretion from b-cells from wild-type (WT) and ABCA1-l/-l mice was similar. Insulin secretion was, however, reduced upon addition of ABCA1 -l/-l serum to the medium compared with WT serum, whereas islets lacking b-cell ABCA1 were not affected differently by ABCA1 -l/-l or WT serum. After high-fat feeding, WT and ABCA1 -l/-l mice showed no difference in glucose tolerance or insulin secretion, and serum from ABCA1 -l/-l and WT mice fed a high-fat diet did not affect insulin secretion differently. We conclude that hepatic ABCA1 improves glucose tolerance by improving b-cell function through both HDL production and interaction with b-cell ABCA1. The beneficial effect of hepatic ABCA1 is decreased under metabolic stress. Increasing hepatic ABCA1 may represent a novel therapeutic strategy for improving glucose homeostasis in diabetes.

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ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity

Cited by 78 publications

References 35 publications

Association of adiponectin gene polymorphism rs266729 with type two diabetes mellitus in Iraqi population. A pilot study

Association of adiponectin gene polymorphism rs266729 with type two diabetes mellitus in Iraqi population. A pilot study

Adipocyte ATP-Binding Cassette G1 Promotes Triglyceride Storage, Fat Mass Growth, and Human Obesity

Hepatic ABCA1 Expression Improves β-Cell Function and Glucose Tolerance

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