Angiotensin Receptor Blocker ameliorates hyperlipidemia and increases lipid utilization in a rat model of metabolic syndrome

Abstract

CD36 and lipoprotein lipase (LPL) are essential proteins involved in lipid mobilization and triglyceride storage in various cell types, including adipocytes. Accumulation of excess lipids in non‐adipose tissues leads to cell dysfunction, potentially cell death, and ultimately insulin resistance. Furthermore, activation of the renin‐angiotensin system (RAS) is implicated in the manifestation of metabolic syndrome, for which dyslipidemia is an associated factor. To address our hypothesis that blockade of the angiotensin II receptor (AT1) can improve lipid utilization, we measured body mass, retroperitoneal mass, adipose lipase activity, CD36 and LPL expression in five groups of rats; 1) Long‐Evans Tokushima Otsuka (LETO) normal diet (ND) (n=6), 2) Otsuka Long‐Evans Tokushima Fatty (OLETF) ND (n=8), 3) OLETF high‐fat diet (HFD, 62% fat in food) (n=8), 4) OLETF + angiotensin receptor blocker (ARB) (10 mg olmesartan/kg/d 6 wk) (n=8), and 5) OLETF HFD + ARB (n=7). Body mass increased 38% in OLETF relative to LETO; ARB decreased it by 20% relative to OLETF, and HFD+ARB decreased it by 37% relative to HFD. ARB decreased retroperitoneal fat 16% in relation to OLETF, and ARB+HFD decreased it 72% compared to HFD. CD36 decreased in response to a HFD and lipase activity increased with ARB treatment. Results suggest that AT1 activation increases lipid utilization, therefore, ameliorating the development of hyperlipidemia from a high fat diet.Support or Funding InformationUC Leadership and Excellence through Advanced Degrees (UC LEADS) United States Department of Agriculture (USDA)