Glutamine deficiency induces lipolysis in adipocytes.

Glutamine is the most abundant amino acid in the body, and adipose tissue is one of the glutamine-producing organs. Glutamine has important and unique metabolic functions; however, its effects in adipocytes are still unclear. 3T3-L1 adipocytes produced and secreted glutamine dependent on glutamine synthetase, but preadipocytes did not. The inhibition of glutamine synthetase by l-methionine sulfoximine (MSO) impaired the differentiation of preadipocytes to mature adipocytes, and this inhibitory effect of MSO was rescued by exogenous glutamine supplementation. Glutamine concentrations were low, and Atgl gene expression was high in epididymal white adipose tissues of fasting mice in vivo. In 3T3-L1 adipocytes, glutamine deprivation induced Atgl expression and increased glycerol concentration in culture medium. Atgl expression is regulated by FoxO1, and glutamine deprivation reduced FoxO1 phosphorylation (Ser256), indicating the activation of FoxO1. These results demonstrate that glutamine is necessary for the differentiation of preadipocytes and regulates lipolysis through FoxO1 in mature adipocytes.