Abstract
Leptin administration enhances lipid oxidation in skeletal muscle. Nevertheless, direct and chronic effect of leptin has not been well characterized. Here, we measured the effect of leptin on skeletal muscles and their signaling pathways using differentiated C(2)C(12) myotubes and primary myotube cultures. Differentiated myotubes expressed both the short and long forms of leptin receptors. Leptin increased lipid oxidation in myotubes in a concentration- and time-dependent manner, with significant induction of lipid oxidation occurring after 6 h. Actinomycin D completely blocked leptin-induced lipid oxidation. Leptin significantly increased phosphorylation of JAK2 and STAT3 in myotubes, and leptin-induced lipid oxidation was abolished by treatment with a JAK2 inhibitor or STAT3 siRNA. We then used mouse myotubes to measure these effects under physiological conditions. Leptin increased lipid oxidation, which again was blocked by a JAK2 inhibitor and STAT3 siRNA. These results suggest that the JAK2/STAT3 signaling pathway may underlie the chronic effects of leptin on lipid oxidation in skeletal muscles.
MeSH terms
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Animals
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Blotting, Western
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Cadherins / genetics
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Cadherins / metabolism
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Cells, Cultured
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Ion Channels / genetics
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Ion Channels / metabolism
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Janus Kinase 2 / antagonists & inhibitors
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Janus Kinase 2 / genetics
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Janus Kinase 2 / metabolism
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Leptin / pharmacology*
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Lipid Peroxidation / drug effects*
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Male
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Mice
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Mice, Inbred C57BL
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Mitochondrial Proteins / genetics
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Mitochondrial Proteins / metabolism
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Muscle Fibers, Skeletal / cytology
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Muscle Fibers, Skeletal / drug effects*
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Muscle Fibers, Skeletal / metabolism
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Muscle, Skeletal / cytology
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Muscle, Skeletal / drug effects*
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Muscle, Skeletal / metabolism*
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Oxidation-Reduction
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Phosphorylation / drug effects
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RNA, Messenger / genetics
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RNA, Messenger / metabolism
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RNA, Small Interfering / pharmacology
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STAT3 Transcription Factor / antagonists & inhibitors
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STAT3 Transcription Factor / genetics
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STAT3 Transcription Factor / metabolism
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Signal Transduction
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Uncoupling Protein 2
Substances
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Cadherins
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Ion Channels
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Leptin
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Mitochondrial Proteins
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RNA, Messenger
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RNA, Small Interfering
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STAT3 Transcription Factor
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Stat3 protein, mouse
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Uncoupling Protein 2
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M-cadherin
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Jak2 protein, mouse
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Janus Kinase 2