Abstract
Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. ABCA1 plays a major role in cholesterol efflux, suggesting a role for ABCA1 in maintaining cholesterol homeostasis in the adipocyte. However, the impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. To address this, we used mice lacking ABCA1 specifically in adipocytes (ABCA1(-ad/-ad)). When fed a high-fat, high-cholesterol diet, ABCA1(-ad/-ad) mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg1, glut-4, adiponectin, and leptin. ABCA1(-ad/-ad) mice also demonstrated impaired glucose tolerance, lower insulin sensitivity, and decreased insulin secretion. We conclude that ABCA1 in adipocytes influences adipocyte lipid metabolism, body weight, and whole-body glucose homeostasis.
Highlights
Adipose tissue contains one of the largest reservoirs of cholesterol in the body
Because ABCA1 is a major mediator of cholesterol efflux [9, 10], we evaluated whether loss of ABCA1 in adipocytes raises adipose cholesterol content
We observed a significant increase in the cholesterol content in Gonadal adipose tissue (GAT), Subcutaneous adipose tissue (SAT), and mesenteric adipose tissue (MAT) in ABCA1Ϫad/Ϫad mice compared with wild-type control mice (ABCA1+/+) on a chow diet (Fig. 1B)
Summary
Adipose tissue contains one of the largest reservoirs of cholesterol in the body. Adipocyte dysfunction in obesity is associated with intracellular cholesterol accumulation, and alterations in cholesterol homeostasis have been shown to alter glucose metabolism in cultured adipocytes. The impact of adipocyte ABCA1 on adipose tissue function and glucose metabolism is unknown. Our aim was to determine the impact of adipocyte ABCA1 on adipocyte lipid metabolism, body weight, and glucose metabolism in vivo. When fed a high-fat, high-cholesterol diet, ABCA1؊ad/؊ad mice showed increased cholesterol and triglyceride stores in adipose tissue, developed enlarged fat pads, and had increased body weight. Associated with these phenotypic changes, we observed significant changes in the expression of genes involved in cholesterol and glucose homeostasis, including ldlr, abcg, glut-4, adiponectin, and leptin. ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity. TGs leave adipose tissue as NEFAs after TG lipolysis [6], while cholesterol is removed from adipocytes via transporters such as ABCA1 and ABCG1 [7, 8]
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