NITRIC OXIDE SYNTHASE INHIBITION DOES NOT ALTER HEPTATIC MITOCHONDRIAL FUNCTION IN NONALCOHOLIC FATTY LIVER DISEASE
R.D. Sheldon, J. Padilla, M.H. Laughlin, FACSM, R.S. Rector. Departments of Internal Medicine-Gastroenterology and Hepatology, Nutrition and Exercise Physiology, and Biomedical Science, University of Missouri, Columbia, MO, and Harry S Truman Memorial VA Hospital, Columbia, MO.
Nitric oxide (NO) is a complex modulator of mitochondrial content and function. In insulin resistance, constitutive NO production is reduced and it is unknown whether this contributes to hepatic mitochondrial dysfunction in nonalcoholic fatty liver disease (NAFLD). Purpose: To test the hypothesis that endogenous NO production abatement with a non-selective NO synthase inhibitor (L-NAME) would reduce hepatic mitochondrial content and function in lean Long-Evans Tokushima Otsuka (LETO) rats and obese, insulin resistant Otsuka Long-Evans Tokushima Fatty (OLETF) rats. Methods: OLETF and LETO rats (16 weeks) received either control or L-NAME (65-70 mg/kg/day) containing drinking water (n=10/group) for 4 weeks. Animals were sacrificed following a 12-hour fast and blood and liver were obtained. Hepatic mitochondria were isolated and fatty acid oxidation (FAO) and respiration were assessed. Results: L-NAME treatment significantly (p < 0.05) reduced serum NO metabolites (NOx) and reduced food intake in both LETO and OLETF rats. Additionally, L-NAME treated OLETF rats, relative to control OLETFs, had significantly reduced percent body fat (24.5% vs. 27.6%) and fasting plasma insulin (22.4±3.1 vs. 32.0±3.8 ng/mL). L-NAME did not alter hepatic mitochondrial respiration, FAO, oxidative phosphorylation complex (OXPHOS I-V) protein content, or PGC-1α protein content. Conclusion: Under the conditions of this study, while systemic NO synthase inhibition reduced circulating NOx levels, there was no observed effects on hepatic mitochondrial content or function in a lean or obese condition. Further work is needed to elucidate the role of NO in mediating mitochondrial function in NAFLD.
This work is supported by a Molecular Life Sciences Fellowship (RDS), NIH grant HL-36088 (MHL), and a VHA-CDA2 BX001299-02 Grant (RSR).
Sheldon, RD; Padilla, J; Laughlin, MH FACSM; and Rector, RS
"NITRIC OXIDE SYNTHASE INHIBITION DOES NOT ALTER HEPTATIC MITOCHONDRIAL FUNCTION IN NONALCOHOLIC FATTY LIVER DISEASE,"
International Journal of Exercise Science: Conference Proceedings:
1, Article 56.
Available at: http://digitalcommons.wku.edu/ijesab/vol11/iss1/56
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