Leptin differentially regulate STAT3 activation in ob/ob mouse adipose mesenchymal stem cells
1 Department of Food Science and Human Nutrition, Michigan State University, East Lansing, Michigan, MI 48824, USA
2 Comparative Medicine and Integrative Biology Graduate Program, College of Veterinary Medicine, Michigan State University, East Lansing, MI, 48824, USA
3 Nutritional Immunology Laboratory, JM USDA HNRC at Tufts University, Boston, MA, 02111, USA
4 Department of Pediatrics and Human Development, Michigan State University, East Lansing, MI, 48824, USA
5 Department of Animal Science, and University of Tennessee Obesity Research Cente, University of Tennessee, Knoxville, TN, 37996, USA
6 Current affiliation: Dana-Farber Cancer Institute, Harvard Medical School, Boston, MA, 02135, USA
7 USDA-ARS, Grand Forks Human Nutrition Research Center, 2420 2nd Ave. N., Stop 9034, Grand Forks, ND 58203, USA
Nutrition & Metabolism 2012, 9:109 doi:10.1186/1743-7075-9-109Published: 5 December 2012
Leptin-deficient ob/ob 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 ex vivo 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 ob/ob mice.
Using leptin deficient ob/ob mice, we investigated whether leptin injection into ob/ob 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.
We report here that adipose stem cell number is significantly increased following leptin injection in ob/ob mice and with treatment of isolated stem cells with leptin in vitro. 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.
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.