Effects of RAS blockers on differentiation and insulin sensitivity of human preadipocytes

Abstract

Objective To study the effects of renin-angiotensin system (RAS) blockers on differentiation and insulin sensitivity of human omental and subcutaneous preadipocytes. Methods Human omental and subcutaneous preadipocytes were isolated from abdominal adipose tissue obtained from 16 healthy adult women undergoing elective abdominal surgery. Preadipocytes were differentiated for 14 days without any treatment (Group NC) or in the presence of either angiotensin converting enzyme inhibitor Benazapril, angiotensin Ⅱ receptor blocker Telmisartan or thiazolidinedione Pioglitazone in serum-free medium. Cell activition, lipid content and glycerol-3-phosphate dehydrogenase (G3PDH) activition of preadipocytes were observed during the differentiation. The amount of glucose consumption was employed to determine the insulin sensitivity of preadipocytes. Results Cell activition, measured by MTT assay, was higher in differentiated subcutaneous preadipocytes than that in omental preadipocytes under basal culture condition (Group NC), while the lipid content of subcutaneous preadipocytes was lower than that of omental ones. There is no difference of insulin sensitivity between subcutaneous and omental preadipocytes in group NC. Most of the metabolic and differentiating parameters were improved significantly by the treament of Benazapril, Telmisartan or Pioglitazone. Furthermore,Telmisartan seemed to be superior to Pioglitazone in inducing differentiation of omental preadipocytes. The G3PDH activition of subcutaneous preadipocytes could only be stimulated by Pioglitazone, and the effects of Telmisartan on G3PDH activition were omental depot-specific. These findings were consistent with the effects of RAS blockers on insulin sensitivity of preadipocytes. The improvement of glucose consumption was significantly greater in Telmisartan-treated human omental preadipocytes compared with Pioglitazone-treated ones[(5.567 ± 1. 612) mmol/L vs. (4.418 ± 1. 572) mmol/L, P =0. 020]. In contrary, it was lower in Telmisartan-treated human subcutaneous preadipocytes compared with Pioglitazone-treated ones [(5. 335 ± 1. 461) mmol/L vs. (7. 506 ± 1. 615)mmol/L, P < 0. 01]. Conclusions Compared with Pioglitazone, Telmisartan and Benazapril have stronger effects on human omental preadipocytes in differentiation and insulin sensitivity. This may suggests a potential benefit of RAS blockers on metabolic syndrome with characteristic intra-abdominal obesity. Key words: Renin-angiotensin system blockers; Thiasolidinedione; Preadipocytes; Cell differentiation; Insulin resistance