Abstract 5537: Inhibition of Pancreatic Lipase and the Renin Angiotensin System Synergistically Decreases Body Fat

Abstract

We have recently demonstrated that mice lacking renin are lean, and excrete more fat in the feces, which is associated with less than 20 % expression of pancreatic lipase and colipase. Treating wild type (WT) mice with an angiotensin receptor blocker losartan (ARB) or an angiotensin converting enzyme (ACE) inhibitor enalapril does not affect body weight, body fat, fecal fat excretion and pancreatic lipase expression, although their colipase expression in the pancreas is decreased to the low levels of the Ren1c −/− mice. Because colipase is necessary for activation of lipase, we hypothesized that inhibition of both pancreatic lipase and colipase by combination of ARB or ACE inhibitor and lipase inhibitor (orlistat) more effectively decreases body weight and body fat than either of them alone. Treating WT mice with both losartan (0.45g/L in drinking water) and orlistat (200 mg/kg diet) for two weeks reduced the body fat significantly more than mice treated with losartan alone or orlistat alone (control 12.5±1.42 %, losartan 8.7±1.9 %, orlistat 3.8±0.8 %, losartan + orlistat 0.2±2.5 %). The fecal fat content in mice treated with losartan and orlistat is also significantly higher than that of mice treated with losartan alone or orlistat alone (control 46.1±6.2 mg/day, losartan 32.0±4.0 mg/day, orlistat 137.1±9.6 mg/day, losartan + orlistat 186.0±39.6 mg/day). We conclude that inhibiting pancreatic lipase and colipase by using combination of lipase inhibitor and ARB or ACE inhibitor is a promising treatment of the metabolic syndrome. This research has received full or partial funding support from the American Heart Association, Mid-Atlantic Affiliate (Maryland, North Carolina, South Carolina, Virginia & Washington, DC).