Capsaicin Induces Metabolic Gene Expression in C2C12 Myotubes

PURPOSE: Capsaicinoids may possess thermic effects resulting in increased energy expenditure, leading some to consume concentrated capsaicin supplements for weight loss. Capsaicin has been shown to activate select molecular targets contributing to increased metabolism, however the effects of capsaicin on many molecular targets have yet to be determined. This study investigated the effects of capsaicin on metabolic gene expression in cultured skeletal muscle. METHODS: C2C12 myotubes were treated with either DMSO control or capsaicin at 0.25μM, 0.5μM, 1.0μM, or 2μM for 24 hours. Gene expression of several regulators of mitochondrial biogenesis and oxidative metabolism including peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), nuclear respiratory factor 1 (NRF1), and mitochondrial transcription factor A (TFAM) were measured via qRT-PCR. Mitochondrial content was quantified via fluorescence which was confirmed visually using fluorescent microscopy. Cellular lipid content was determined by oil red o colorimetric staining. RESULTS: Gene expression experiments identified capsaicin at 0.5μM to be the most optimal concentration for inducing myotube mitochondrial biogenesis. Specifically, capsaicin at 0.5μM significantly elevated PGC-1α (18.6 fold ±14.5), NRF1 (4.6 fold ±1.7), and TFAM (5.0 fold ±2.3) gene expression following 24-hour treatment. Cells treated with capsaicin at 0.5μM also exhibited significantly greater mitochondrial staining (7.5% ±4.5%). Moreover, capsaicin induced the expression of several related metabolic genes such as Forkhead Box O1 (Foxo1) and Sirtuin 3 (Sirt3). Lastly, despite unaltered peroxisome proliferator-activated receptor gamma (PPARγ) expression, capsaicin-treated cells exhibited significantly reduced lipid content suggesting lipid oxidation may be enhanced following capsaicin treatment. CONCLUSION: Capsaicin appears to stimulate several genes which govern mitochondrial biogenesis and cellular energetics. These findings suggest capsaicin may provide metabolic benefits, however, these data require verification at the protein and functional level.