Hepatocyte-specific phgdh-deficient mice culminate in mild obesity, insulin resistance, and enhanced vulnerability to protein starvation

Momoko Hamano, Kayoko Esaki, Kazuki Moriyasu, Tokio Yasuda, Sinya Mohri, Kosuke Tashiro, Yoshio Hirabayashi, Shigeki Furuya

研究成果: Contribution to journalArticle査読

抄録

L-Serine (Ser) is synthesized de novo from 3-phosphoglycerate via the phosphorylated pathway committed by phosphoglycerate dehydrogenase (Phgdh). A previous study reported that feeding a protein-free diet increased the enzymatic activity of Phgdh in the liver and enhanced Ser synthesis in the rat liver. However, the nutritional and physiological functions of Ser synthesis in the liver remain unclear. To clarify the physiological significance of de novo Ser synthesis in the liver, we generated liver hepatocyte-specific Phgdh KO (LKO) mice using an albumin-Cre driver. The LKO mice exhibited a significant gain in body weight compared to Floxed controls at 23 weeks of age and impaired systemic glucose metabolism, which was accompanied by diminished insu-lin/IGF signaling. Although LKO mice had no apparent defects in steatosis, the molecular signatures of inflammation and stress responses were evident in the liver of LKO mice. Moreover, LKO mice were more vulnerable to protein starvation than the Floxed mice. These observations demonstrate that Phgdh-dependent de novo Ser synthesis in liver hepatocytes contributes to the maintenance of systemic glucose tolerance, suppression of inflammatory response, and resistance to protein starva-tion.

本文言語英語
論文番号3468
ジャーナルNutrients
13
10
DOI
出版ステータス出版済み - 10 2021

All Science Journal Classification (ASJC) codes

  • 食品科学
  • 栄養および糖尿病

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