Chronic Leptin Administration Down-Regulates Rat Skeletal Muscle Pyruvate Dehydrogenase Activity

• Published in: Canadian journal of applied physiology 2003-01, Vol.28, p.S60-S60
• Main Authors: Grant, S C, Slack, J P, Armstrong, S P, Steinberg, G R, Dyck, D J, Peters, S J
• Format: Article
• Language: English
• ISSN: 1066-7814

Elevated plasma leptin concentrations stimulate skeletal muscle fatty acid oxidation; however, the precise mechanism(s) involved remain unclear. Chronically elevated leptin levels decrease plasma insulin, so the purpose of this study was to examine the effect of leptin on PDH activation and PDH kinase (PDK) activity with and without normal levels of insulin. Rats were infused with: leptin (L); insulin (I); leptin + insulin (L+I); or saline (control [C]). They were pair fed (PF) for 4 days. PDHa activity decreased significantly in the L group compared to C and I (0.10 plus or minus 0.02 vs. 0.42 plus or minus 0.10 and 0.97 plus or minus 0.19 mmol/min/kg), but this effect was reversed when normal insulin levels were maintained (L+I). PDK activity appeared to increase in L compared to C (p = 0.067). Results suggest that increased PDK activity and decreased carbohydrate oxidation through PDH contributes to the increase in fat oxidation observed with elevated plasma leptin concentrations. However, leptin-induced down-regulation of carbohydrate metabolism was opposed by normal insulin concentrations.