Leptin differentially regulate STAT3 activation in <it>ob/ob</it> mouse adipose mesenchymal stem cells

• Main Authors: Zhou Zhou, Neupane Manish, Zhou Hui, Wu Dayong, Chang Chia-Cheng, Moustaid-Moussa Naima, Claycombe Kate J
• Format: Article
• Language: English
• Published: BMC 2012-12-01
• Series: Nutrition & Metabolism
• Subjects: Obesity; Adipose stem cell; Leptin
• Online Access: http://www.nutritionandmetabolism.com/content/9/1/109

<p>Abstract</p> <p>Background</p> <p>Leptin-deficient <it>ob/ob</it> mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes <it>ex vivo</it> and thereby contribute toward increased adipocyte cell numbers, obesity, and inflamm ation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in <it>ob/ob</it> mice.</p> <p>Methods</p> <p>Using leptin deficient <it>ob/ob</it> mice, we investigated whether leptin injection into <it>ob/ob</it> mice increases adipose stem cell numbers and adipose tissue inflammatory marker MCP-1 mRNA and secretion levels. We also determined leptin mediated signaling pathways in the adipose stem cells.</p> <p>Results</p> <p>We report here that adipose stem cell number is significantly increased following leptin injection in <it>ob/ob</it> mice and with treatment of isolated stem cells with leptin <it>in vitro</it>. Leptin also up-regulated MCP-1 secretion in a dose- and time-dependent manner. We further showed that increased MCP-1 mRNA levels were due to increased phosphorylation of Signal Transducer and Activator of Transcription 3 (STAT3) Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells.</p> <p>Conclusions</p> <p>Taken together, these studies demonstrate that leptin increases adipose stem cell number and differentially activates STAT3 protein resulting in up-regulation of MCP-1 gene expression. Further studies of mechanisms mediating adipose stem cell hyperplasia and leptin signaling in obesity are warranted and may help identify novel anti-obesity target strategies.</p>