Involvement of nitric oxide and cyclooxygenase-derived metabolites as mediators of fish oil metabolic actions

Abstract

Omega 3 polyunsaturated fatty acids (n-3 PUFAs), found in the fish oil, attenuate obesity and associated metabolic complications such as inflammation, insulin resistance and hyperlipidemia in rodents. In a pilot study performed in diet induced obese mice, intake a diet produced with fish oil (HFn3) reduced body weight gain and improved glucose homeostasis. To elucidate the mechanisms underlying these HFn3 effects, we propose to investigate the involvement of nitric oxide (NO) and cyclooxygenase (Cox) metabolites, both of which enhanced by n-3 PUFAs, as mediators of HFn3 actions. For this, C57BL6/J mice fed during 8 weeks with a high fat diet produced with lard (HFD) to induce obesity will be either maintained in the same HFD diet, or fed with a isocaloric HFn3 diet associated or not treatment with either vehicle or NO synthase inhibitor N-É-nitro-l-arginina (LNNA 250 mg/L), or Cox inhibitor acetylsalicylic acid (aspirin, 5 mg/kg/day) in the drinking water during 4 weeks and evaluated for body weight and composition, energy expenditure, locomotor activity, food and water intakes, serum lipid and metabolite profile, glucose homeostasis (GTT, ITT and PTT), insulin signaling (Akt phosphorylation), inflammation and expression of NO synthase and Cox isoforms in adipose tissue and tail vasodilation.