Recent studies have shown a role of inflammation in muscle atrophy and sarcopenia. However, no anti-inflammatory pharmacotherapy has been established for the treatment of sarcopenia. Here, we investigate the potential role of PPARα and its ligands on inflammatory response and PGC-1α gene expression in LPS-treated C2C12 myotubes. Knockdown of PPARα, whose expression was upregulated upon differentiation, augmented IL-6 or TNFα gene expression. Conversely, PPARα overexpression or its activation by ligands suppressed 2-h LPS-induced cytokine expression, with pemafibrate attenuating NF-κB or STAT3 phosphorylation. Of note, reduction of PGC-1α gene expression by LPS treatment for 24 hours was partially reversed by fenofibrate. Our data demonstrate a critical inhibitory role of PPARα in inflammatory response of C2C12 myotubes and suggest a future possibility of PPARα ligands as a candidate for anti-inflammatory therapy against sarcopenia.
PPAR alpha , Sarcopenia , Anti-Inflammatory Agents/metabolism , Lipopolysaccharides/metabolism , Muscle Fibers, Skeletal/metabolism , NF-kappa B/metabolism , PPAR alpha/metabolism , Sarcopenia/metabolism , Animals , Mice
Smoking cessation increases body weight. The underlying mechanisms, however, have not been fully understood. We here report an establishment of a mouse model that exhibits an augmented body weight gain after nicotine withdrawal. High fat diet-fed mice were infused with nicotine for two weeks, and then with vehicle for another two weeks using osmotic minipumps. Body weight increased immediately after nicotine cessation and was significantly higher than that of mice continued on nicotine. Mice switched to vehicle consumed more food than nicotine-continued mice during the first week of cessation, while oxygen consumption was comparable. Elevated expression of orexigenic agouti-related peptide was observed in the hypothalamic appetite center. Pair-feeding experiment revealed that the accelerated weight gain after nicotine withdrawal is explained by enhanced energy intake. As a showcase of an efficacy of pharmacologic intervention, exendin-4 was administered and showed a potent suppression of energy intake and weight gain in mice withdrawn from nicotine. Our current model provides a unique platform for the investigation of the changes of energy regulation after smoking cessation.
Nicotine/adverse effects , Substance Withdrawal Syndrome/pathology , Weight Gain , Agouti-Related Protein/metabolism , Animals , Calorimetry , Cell Respiration/drug effects , Disease Models, Animal , Energy Intake/drug effects , Exenatide/pharmacology , Feeding Behavior/drug effects , Gene Expression Regulation/drug effects , Hypothalamus/metabolism , Male , Mice, Inbred C57BL , RNA, Messenger/genetics , RNA, Messenger/metabolism , Substance Withdrawal Syndrome/genetics , Weight Gain/drug effects , Weight Gain/genetics
