Glutamine deficiency suppresses adipogenic differentiation in vitro

Abstract

Glutamine (Gln) is the major source of energy in cells after glucose and has recently been shown to be an important carbon source for de novo lipogenesis1. To investigate whether Gln status affects adipocyte differentiation, mouse mesenchymal stem cells (MSCs) were subjected to Gln deprivation during differentiation and compared with MSCs differentiated in Gln-supplemented medium (5, 10, and 20 mM). Gln deprivation decreased adipogenic differentiation and lipid droplet formation, intracellular Gln concentration and gene expression for classic adipogenic markers including PPARγ. Also, glutamine restriction suppressed gene expression of isocitrate dehydrogenase 1 (IDH1), an enzyme that produces citrate for lipid synthesis. In contrast, Gln supplementation promoted adipogenic differentiation in a dose-dependent manner. These results suggest that the Gln pathway may have a previously overlooked role in adipogenesis. The underlying mechanism involving the Gln-IDH1 pathway may represent a potential therapeutic strategy to treat excessive lipid accumulation and, consequently, obesity.