Co-Administration of Nitrite and Conjugated Linoleic Acid Attenuates Cardiac Dysfunction in Leptin Deficient Mice.

PIELL KM, SALVATORE SR, BONACCI G, SCHOPFER FJ, AND COLE MP

Atlanta, GA

Congreso; 18th Annual Meeting of the Society for Free Radical Biology and Medicine (SFRBM); 2011

Society for Free Radical Biology and Medicine (SFRBM)

Nitrite-derived oxidative inflammatory reactions lead to nitration of unsaturated fatty acids. Nitrated fatty acids (NO2-FA) are electrophilic and mediate anti-inflammatory actions through modulation of lipid receptors and transcription factors, such as PPAR-, conferring adaptive changes in metabolic and inflammatory status resulting in alteration of gene expression. It was hypothesized that co-administration of conjugated linoleic acid (cLA) + nitrite would attenuate left ventricular (LV) cardiac dysfunction in leptin deficient (ob/ob) mice. Echocardiography was used to image a significant decrease in percent fractional shortening (%FS) in aged ob/ob mice, as compared to WT (19.4±8.8% vs. 34.6±6.5%, p=0.0005). Following treatment with cLA (20mg/kg/d) via osmotic mini-pump + nitrite (50ppm drinking water), re-imaging of ob/ob mice demonstrated a significant improvement in LV function, comparable to that of WT (p=0.02). There was no change in weight gain (6 week treatment) in ob/ob or WT mice across treatment groups. Measurement of plasma cLA using electrospray ionizationtandem mass spectrometry (ESI MS/MS) revealed that ob/ob mice have increased levels than that of WT (59.9􀁲28.2nM vs.32.9±15.5nM). Chemiluminescence quantification demonstrated that plasma nitrate levels were lower in ob/ob mice compared to WT (3.5±1.1M vs. 40.5±14.5M, p=0.0057), however plasma nitrate increased in nitrite- and nitrite + cLA-treated animals. Administration of nitrite + cLA increased the protein expression of HSP70 in both WT and ob/ob cardiac tissue, while PPAR- was inversely affected across genotypes. Altogether, these findings support that co-delivery of nitrite + cLA modulates lipid metabolism and stress signaling pathways in vivo, similar to NO2-FA mediated cell signaling, providing cardiac tissue protection in leptin deficient mice.