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

نویسندگان

  • Willeke de Haan
  • Alpana Bhattacharjee
  • Piers Ruddle
  • Martin H Kang
  • Michael R Hayden
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

[Role of leptin in the regulation of lipid and carbohydrate metabolism].

Leptin is a hormone secreted primarily by adipose tissue and its blood levels depend on the amount of fat stored in adipocytes. Leptin has a wide range of physiological effects. Acting directly or through the sympathetic nervous system it participates in the regulation of energy metabolism. Leptin inhibits synthesis of triacylglycerols in the liver, adipose tissue and skeletal muscles, thus red...

متن کامل

Novel mechanisms by which fat cells regulate systemic insulin sensitivity and diabetes risk

The adipose cell functions as an endocrine organ in addition to its role in energy storage. Adipocytes secrete hormones, cytokines and other factors that influence energy balance, glucose homeostasis, insulin sensitivity and vascular biology through effects in peripheral tissues and the central nervous system. In humans with obesity and type 2 diabetes, expression of the Glut4 glucose transport...

متن کامل

Expression of Human Chemerin Induces Insulin Resistance in the Skeletal Muscle but Does Not Affect Weight, Lipid Levels, and Atherosclerosis in LDL Receptor Knockout Mice on High-Fat Diet

OBJECTIVE Chemerin is a recently discovered hepatoadipokine that regulates adipocyte differentiation as well as chemotaxis and activation of dendritic cells and macrophages. Chemerin was reported to modulate insulin sensitivity in adipocytes and skeletal muscle cells in vitro and to exacerbate glucose intolerance in several mouse models in vivo. In humans, chemerin was shown to be associated wi...

متن کامل

Sex and Depot Differences in Adipocyte Insulin Sensitivity and Glucose Metabolism

OBJECTIVE To investigate how insulin sensitivity and glucose metabolism differ in adipocytes between different fat depots of male and female mice and how sex steroids contribute to these differences. RESEARCH DESIGN AND METHODS Adipocytes from intra-abdominal/perigonadal (PG) and subcutaneous (SC) adipose tissue from normal, castrated, or steroid-implanted animals were isolated and analyzed f...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:
  • Journal of lipid research

دوره 55 3  شماره 

صفحات  -

تاریخ انتشار 2014