Nesfatin-1 promotes brown adipocyte phenotype.
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.
Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
Yuexin
Y
Wang
Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Ziru
Z
Li
Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
Xinyu
X
Zhang
Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
Xinxin
X
Xiang
Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.
Yin
Y
Li
Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Michael W
MW
Mulholland
Department of Physiology and Pathophysiology, Peking University Health Science Center and Key Laboratory of Molecular Cardiovascular Science, Ministry of Education, Beijing 100191, China.|Department of Surgery, University of Michigan Medical Center, Ann Arbor, MI 48109, USA.
Weizhen
W
Zhang
D052437:Adipocytes, Brown / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D002454:Cell Differentiation / Q000187:drug effects*; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D017353:Gene Deletion; D005786:Gene Expression Regulation; D007930:Leucine / Q000494:pharmacology; D008049:Lipase / Q000235:genetics / Q000378:metabolism; D008066:Lipolysis / Q000187:drug effects* / Q000235:genetics; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D025261:Mitochondrial Proton-Translocating ATPases / Q000235:genetics / Q000378:metabolism; D009419:Nerve Tissue Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D000080866:Nucleobindins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha / Q000235:genetics / Q000378:metabolism; D010641:Phenotype; D010766:Phosphorylation / Q000187:drug effects; D061251:Primary Cell Culture; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D038744:Ribosomal Protein S6 Kinases, 90-kDa / Q000235:genetics / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects* / Q000235:genetics; D058570:TOR Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins / Q000235:genetics / Q000378:metabolism; D000071256:Uncoupling Protein 1 / Q000235:genetics / Q000378:metabolism; D000217:Acyltransferases
D002135:Calcium-Binding Proteins; D004268:DNA-Binding Proteins; D007930:Leucine; D008049:Lipase; D025261:Mitochondrial Proton-Translocating ATPases; D009419:Nerve Tissue Proteins; D000080866:Nucleobindins; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D012333:RNA, Messenger; D038744:Ribosomal Protein S6 Kinases, 90-kDa; D058570:TOR Serine-Threonine Kinases; D014157:Transcription Factors; D000077004:Tuberous Sclerosis Complex 1 Protein; D025521:Tumor Suppressor Proteins; D000071256:Uncoupling Protein 1; C000630651:Nucb1 protein, mouse; C485290:Ppargc1a protein, mouse; C521133:Prdm16 protein, mouse; C000624651:Tsc1 protein, mouse; C000604372:Ucp1 protein, mouse; C546843:mTOR protein, mouse; C512964:Rps6ka1 protein, mouse; C494445:PNPLA2 protein, mouse; D000217:Acyltransferases; C530489:ATP5b protein, mouse