Effects of Endogenous PPAR Agonist Nitro-Oleic Acid on Metabolic Syndrome in Obese Zucker Rats.

Nitroalkene derivatives of nitro-oleic acid (OA-NO(2)) are endogenous lipid products with novel signaling properties, particularly the activation of PPARs. The goal of this proposal was to examine the therapeutic potential of this OA-NO(2) in treatment of obesity and obesity-related conditions in obese Zucker rats. The animals were randomly divided to receive OA-NO(2), oleic acid (OA), both at 7.5 mug/kg/d, or vehicle ethanol via osmotic mini-pumps for 2 weeks. Following OA-NO(2) treatment, food intake was decreased as early as the first day and this effect appeared to persist throughout the experimental period. At day 14, body weight gain was significantly reduced by OA-NO(2) treatment. This treatment significantly reduced plasma triglyceride and almost normalized plasma free fatty acid and significantly increased plasma high-density lipid (HDL). The plasma TBARS and proteinuria were paralelly decreased. In contrast, none of these parameters were affected by OA treatment. After 14 days of OA-NO(2) treatment, hematocrit, a surrogate of fluid retention associated with PPARgamma agonists, remained unchanged. Together, these data demonstrated that OA-NO(2) may offer an effective and safe therapeutic intervention for obesity and obesity-related conditions.