Obesity Is Associated With Increased Expression of Very Low Density Lipoprotein Receptor in Adipose Tissue: A Possible Link to Increased VLDL Catabolism and Adiposity

Abstract

BACKGROUNDVery‐low density lipoprotein receptor (VLDLR) is a member of the low‐density lipoprotein receptor family highly expressed in adipose tissue. It binds a variety of ligands including apolipoprotein E‐containing triglyceride‐rich lipoproteins, and plays a significant role in the catabolism of triglyceride‐rich lipoproteins. The role of VLDLR had been demonstrated in cell culture and animal models, but little is known about its regulation in human. The objective of this study was to assess the impact of obesity on VLDLR expression in adipose tissue, and to evaluate the role of VLDLR in human adipocyte differentiation and lipid deposition.SUBJECTS AND SAMPLESPaired subcutaneous and visceral adipose tissue aliquots, as well as blood samples, were obtained from a total of 76 subjects, 16 lean (body mass index: BMI ≤ 24.9 kg/m2), 18 overweight (25 ≤ BMI ≤ 29.9 kg/m2) and 42 obese and morbid obese (BMI ≥ 30 kg/m2) subjects. Concentration of plasma lipids (triglycerides, free fatty acids and cholesterol) and glucose was measured enzymatically. Blood insulin level was assayed by enzyme‐linked immunosorbent assay, and homeostasis model assessment of insulin resistance (HOMA‐IR) was determined. Adipocyte size was examined in hematoxylin and eosin‐stained sections, and VLDLR expression was analyzed in adipose tissue using Western blotting and RT‐PCR. In addition, VLDLR expression was examined in isolated pre‐adipocytes before differentiation and during differentiation to mature adipocytes.RESULTSCompared to lean subjects, VLDLR protein level and mRNA abundance in subcutaneous adipose tissue, was up‐regulated in overweight (+46%) and obese subjects (+119%). Similarly, VLDLR expression was up‐regulated in visceral fat but to lesser extent than subcutaneous fat. The abundance of VLDLR mRNA in subcutaneous adipose tissue was positively (p < 0.05) associated with BMI and HOMA‐IR, but not with blood lipids. In addition, VLDLR expression in subcutaneous fat was significantly (p<0.05) associated with increased adipocyte size and triglyceride content. In pre‐adipocytes, VLDLR protein level was virtually inexistent, but increased gradually during differentiation to reach a maximum level in mature adipocytes. Moreover, induction of VLDLR expression in differentiated adipocytes was associated with increased deposition of triglycerides derived mainly from VLDL.CONCLUSIONThe study indicates that obesity up‐regulates VLDLR expression in adipose tissue, and that induction of VLDLR expression during pre‐adipocyte differentiation is associated with increased lipid deposition suggesting a possible role of VLDLR in adipose tissue expansion in human.Support or Funding InformationHackensack University Medical Center