Glucose Fattens Up Muscle

Both adipose tissue and muscle tissue contain stem cells that can differentiate into adipocytes. Because increased concentrations of circulating glucose are associated with increased adiposity, Aguiari et al . investigated whether glucose exposure was sufficient to drive stem cell differentiation. The authors exposed stem cells isolated from human adipose tissue or neonatal rat muscle to medium containing low (5.5 mM) or high (25 mM) concentrations of glucose and found that higher concentrations of glucose increased the proportion of cells adopting an adipocyte phenotype. High concentrations of glucose stimulated the production of reactive oxygen species and activation (translocation to the plasma membrane) of protein kinase Cβ (PKCβ). Addition of hydrogen peroxide to low glucose-containing medium stimulated differentiation of muscle-derived stem cells into adipocytes, whereas inhibition of PKCβ activity through RNAi techniques blocked differentiation of the muscle-derived stem cells into adipocytes. Overexpression of PKCβ increased the proportion of cells adopting the adipocyte phenotype. Adipose-derived stem cells differentiated on sponge supports in high-glucose-containing medium were successfully introduced into nude rats; the tissue became vascularized, and morphological characterization upon surgical removal revealed that this tissue contained adipocytes, preadipocytes, and capillaries. Thus, high circulating concentrations of glucose--a common cause of obesity and a condition associated with diabetes--may be a key factor causing not only the expansion of adipose tissue but also the differentiation of nonadipose tissue, such as muscle or (as has been previously reported) pancreatic β cells, into adipocytes. P. Aguiari, S. Leo, B. Zavan, V. Vindigni, A. Rimessi, K. Bianchi, C. Franzin, R. Cortivo, M. Rossato, R. Vettor, G. Abatangelo, T. Pozzan, P. Pinton, R. Rizzuto, High glucose induces adipogenic differentiation of muscle-derived stem cells. Proc. Natl. Acad. Sci. U.S.A 105 , 1226-1231 (2008). [Abstract] [Full Text]