|ZHOU, ZHOU - Michigan State University|
|NEUPANE, MANISH - Michigan State University|
|ZHOU, HUI REN - Michigan State University|
|WU, DAYONG - Tufts University|
|CHANG, CHIA-CHENG - Michigan State University|
|MOUSTAID-MOUSSA, NAIMA - University Of Tennessee|
Submitted to: Nutrition and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/17/2012
Publication Date: 12/5/2012
Citation: Zhou, Z., Neupane, M., Zhou, H., Wu, D., Chang, C., Moustaid-Moussa, N., Claycombe, K.J. 2012. Leptin differentially regulates STAT3 activation in the ob/ob mice adipose mesenchymal stem cells. Nutrition and Metabolism. 9:109.
Interpretive Summary: Genetically obese ob/ob mice have significantly higher adipose tissue weight as well as significantly increased numbers of differentiated fat cells. Increasing numbers of recent studies have shown that adult stem cells that are isolated from adipose tissue can differentiate into adipocytes which then can lead to increased adipocyte cell numbers, adipose tissue weight, and consequently obesity. However, currently no data are available to discern whether the number of adipose tissue stem cells is increased in ob/ob mice proportionally to their adipose tissue weight. Furthermore, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice. Thus, the objective of this work was to investigate if obesity associated hormones such as leptin that is injected to leptin deficient ob/ob mice increases adipose stem cell number and mRNA levels for an adipose tissue inflammatory marker such as MCP-1. The second objective of this study is to characterize adipose stem cells and their leptin signaling pathways. Identification of adipose stem cells which increase their numbers and inflammation with obesity as well as identifying the signaling pathway regulators of inflammation and obesity may help in the development of anti-obesity target strategies.
Technical Abstract: Leptin-deficient genetically obese ob/ob mice exhibit adipocyte hypertrophy and hyperplasia as well as elevated adipose tissue and systemic inflammation. Studies have shown that multipotent stem cells isolated from adult adipose tissue can differentiate into adipocytes ex vivo and thereby contribute toward increased adipocyte cell numbers, obesity, and inflammation. Currently, information is lacking regarding regulation of adipose stem cell numbers as well as leptin-induced inflammation and its signaling pathway in ob/ob mice. Thus, the objective of this work was to 1. investigate if leptin injection into ob/ob mice increases adipose stem cell number and mRNA levels for an adipose tissue inflammatory marker such as MCP-1; and 2. to characterize adipose stem cells and their leptin signaling pathways. We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice. 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 (STAT) 3 Ser727 but not STAT3 Tyr705 phosphorylation, suggesting differential regulation of MCP-1 gene expression under basal and leptin-stimulated conditions in adipose stem cells. Taken together, these studies demonstrate that leptin differentially activates STAT3 protein in adipose stem cells, 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.