Abstract
Nesfatin-1, an 82 amino acid gastric peptide, is involved in regulation of food uptake and in multiple metabolic activities. Whether nesfatin-1 modulates the differentiation and lipid metabolism of brown adipocytes remains unknown. In the present study, we found that nesfatin-1 mRNA and protein were detectable in isolated brown adipocytes and gradually decreased during differentiation (95% CI 0.6057 to 1.034, p = 0.0001). The decrease in nesfatin-1 was associated with a significant reduction in p-S6. Exposure to nesfatin-1 promoted differentiation of brown adipocytes as revealed by a significant increase in UCP1 mRNA (p = 0.03) and lipolysis-related ATGL mRNA (p = 0.04). Nesfatin-1 attenuated phosphorylation of S6K and S6 during brown adipocyte differentiation. Activation of mTOR by leucine or deletion of TSC1 decreased expression of brown adipocyte-related genes UCP1, UCP3, PGC1α and PRDM16, as well as COX8B and ATP5B. Both leucine and TSC1 deletion blocked nesfatin-1-induced up-regulation of UCP1, PGC1α, COX8B and ATP5B in differentiated brown adipocytes. In conclusion, nesfatin-1 promotes the differentiation of brown adipocytes likely through the mTOR dependent mechanism.
Highlights
Nesfatin-1, an 82 amino acid gastric peptide, is involved in regulation of food uptake and in multiple metabolic activities
To investigate whether the expression of nesfatin-1 changes during the differentiation of brown adipocytes, differentiation of primary brown adipocytes was induced as described in the methods section, and levels of nesfatin-1 mRNA were detected at 8 h, 1, 2, and 4 days
The present study demonstrates that nesfatin-1 is present in brown adipocytes and that nesfatin-1 promotes differentiation of primary brown adipocytes likely through the mechanistic target of rapamycin (mTOR) dependent mechanism
Summary
Nesfatin-1, an 82 amino acid gastric peptide, is involved in regulation of food uptake and in multiple metabolic activities. Exposure to nesfatin-1 promoted differentiation of brown adipocytes as revealed by a significant increase in UCP1 mRNA (p = 0.03) and lipolysis-related ATGL mRNA (p = 0.04). Activation of mTOR by leucine or deletion of TSC1 decreased expression of brown adipocyte-related genes UCP1, UCP3, PGC1α and PRDM16, as well as COX8B and ATP5B Both leucine and TSC1 deletion blocked nesfatin-1-induced up-regulation of UCP1, PGC1α, COX8B and ATP5B in differentiated brown adipocytes. In addition to anorexic effect, nesfaitn-1 has been reported to regulate lipid metabolism, insulin secretion and glucose homeostasis, stress responses, and reproduction[9]. These actions are proposed to be mediated through a central mechanism, with the stomach as the main source of circulating nesfatin-1. Nesfatin-1 promotes the brown adipocyte phenotype, in part by inhibiting mTOR signaling
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