Fatty Acid Oxidation and Triacylglycerol Hydrolysis Are Enhanced Following Chronic Leptin Treatment in Rats

Leptin acutely increases fatty acid (FA) oxidation and triacylglycerol (TG) hydrolysis, and decreases TG esterification in oxidative rodent muscle. However, the effects of chronic leptin administration on FA metabolism in skeletal muscle have not been examined. We hypothesized that chronic leptin treatment would enhance TG hydrolysis as well as the capacity to oxidize FA in soleus (SOL) muscle. Female Sprague-Dawley rats were infused for 2 wks with leptin (LEPT; 0.5mg/kg/d) using subcutaneously implanted mini-osmotic pumps. Control (AD-S) and pairfed (PF-S) animals received saline-filled implants. Subsequently, FA metabolism was monitored for 45 min in isolated, resting and contracting (20 tetani/min) SOL muscles, using pulse-chase procedures. Food intake (-33 ± 2%, p<0.01) and body mass (-12.5 ± 4%, p=0.01) were reduced in both LEPT and PF-S animals. Leptin levels were elevated (+418% ± 7%, p<0.001) in treated animals, but reduced in PF-S animals (-73% ± 8%, p<0.05) relative to controls. At rest, TG hydrolysis was increased in leptin treated rats (1.8 ± 2.2, AD-S vs. 23.5 ± 8.1 nmol/g wet wt., LEPT; p<0.001). In contracting SOL muscles, TG hydrolysis (1.5 ± 0.6, AD-S. vs. 3.6 ± 1.0 μmol/g wet wt, LEPT; p=0.02) and palmitate oxidation (18.3 ± 6.7, AD-S vs. 45.7 ± 9.9 nmol/g wet wt, LEPT; p<0.05) were both significantly increased by leptin treatment. Chronic leptin treatment had no effect on TG esterification either at rest or during contraction. Markers of overall (citrate synthase, CS) and FA (hydroxy-acyl-CoA dehydrogenase, β-HAD) oxidative capacity were unchanged with leptin treatment. Protein expression of hormone sensitive lipase (HSL) was also unaltered following leptin treatment. Thus, leptin-induced increases in lipolysis are likely due to HSL activation (i.e. phosphorylation). Increased FA oxidation secondary to chronic leptin treatment is not due to an