
AbstractNesfatin-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.
Lipolysis, Calcium-Binding Proteins, Primary Cell Culture, Cell Differentiation, Mice, Transgenic, Nerve Tissue Proteins, Lipase, Mitochondrial Proton-Translocating ATPases, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Article, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Adipocytes, Brown, Phenotype, Gene Expression Regulation, Leucine, Animals, Nucleobindins, Phosphorylation, Gene Deletion
Lipolysis, Calcium-Binding Proteins, Primary Cell Culture, Cell Differentiation, Mice, Transgenic, Nerve Tissue Proteins, Lipase, Mitochondrial Proton-Translocating ATPases, Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha, Article, DNA-Binding Proteins, Mice, Inbred C57BL, Mice, Adipocytes, Brown, Phenotype, Gene Expression Regulation, Leucine, Animals, Nucleobindins, Phosphorylation, Gene Deletion
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