ABCA1 in adipocytes regulates adipose tissue lipid content, glucose tolerance, and insulin sensitivity.
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.
Centre for Molecular Medicine and Therapeutics, University of British Columbia, Vancouver, BC, Canada.
Willeke
W
de Haan
Alpana
A
Bhattacharjee
Piers
P
Ruddle
Martin H
MH
Kang
Michael R
MR
Hayden
D064286:ATP Binding Cassette Transporter 1 / Q000172:deficiency* / Q000235:genetics; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism*; D015153:Blotting, Western; D001835:Body Weight; D002784:Cholesterol / Q000378:metabolism; D059305:Diet, High-Fat; D015870:Gene Expression; D005947:Glucose / Q000378:metabolism; D051275:Glucose Transporter Type 4 / Q000235:genetics / Q000378:metabolism; D006706:Homeostasis / Q000235:genetics; D007333:Insulin Resistance; D020738:Leptin / Q000235:genetics / Q000378:metabolism; D008055:Lipids / Q000032:analysis* / Q000097:blood; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D054409:Nicotinamide Phosphoribosyltransferase / Q000235:genetics / Q000378:metabolism; D011973:Receptors, LDL / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014280:Triglycerides / Q000378:metabolism
D064286:ATP Binding Cassette Transporter 1; D001786:Blood Glucose; D002784:Cholesterol; D005947:Glucose; D051275:Glucose Transporter Type 4; D020738:Leptin; D008055:Lipids; D054409:Nicotinamide Phosphoribosyltransferase; D011973:Receptors, LDL; D014280:Triglycerides; C577833:Abca1 protein, mouse; C495693:Slc2a4 protein, mouse
ATP binding cassette transporter A1; cholesterol; glucose homeostasis; insulin resistance; lipid metabolism; obesity; type 2 diabetes