Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Department of Metabolic Medicine, Osaka University Graduate School of Medicine, Suita, Osaka, Japan; Department of Adipose Management, Osaka University Graduate School of Medicine, Suita, Osaka, Japan.
Biochem Biophys Res Commun. 2021 Dec 31;585:155-161. doi: 10.1016/j.bbrc.2021.11.043. Epub 2021 Nov 13.
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.
谷氨酰胺是体内最丰富的氨基酸，脂肪组织是产生谷氨酰胺的器官之一。谷氨酰胺具有重要而独特的代谢功能；然而，其在脂肪细胞中的作用尚不清楚。3T3-L1 脂肪细胞通过谷氨酰胺合成酶产生和分泌谷氨酰胺，但前脂肪细胞则不会。L-蛋氨酸亚砜（MSO）抑制谷氨酰胺合成酶会损害前脂肪细胞向成熟脂肪细胞的分化，而外源性补充谷氨酰胺可以挽救 MSO 的这种抑制作用。在体内禁食小鼠的附睾白色脂肪组织中，谷氨酰胺浓度较低，Atgl 基因表达较高。在 3T3-L1 脂肪细胞中，谷氨酰胺剥夺诱导 Atgl 表达并增加培养基中的甘油浓度。Atgl 的表达受 FoxO1 调控，谷氨酰胺剥夺会降低 FoxO1 磷酸化（Ser256），表明 FoxO1 的激活。这些结果表明，谷氨酰胺是前脂肪细胞分化所必需的，并且通过成熟脂肪细胞中的 FoxO1 调节脂肪分解。
