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Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease

Title
Downregulation of PHGDH expression and hepatic serine level contribute to the development of fatty liver disease
Author
전대원
Keywords
3-Phosphoglycerate dehydrogenase (PHGDH); Serine; High-fat diet; Non-alcoholic fatty liver disease (NAFID); NRF2; SIRT1
Issue Date
2020-01
Publisher
W B SAUNDERS CO-ELSEVIER INC
Citation
METABOLISM-CLINICAL AND EXPERIMENTAL, No. 102, article no. 154000
Abstract
Objective: Supplementation with serine attenuates alcoholic fatty liver by regulating homocysteine metabolism and lipogenesis. However, little is known about scrine metabolism in fatty liver disease (FLD). We aimed to investigate the changes in serine biosynthetic pathways in humans and animal models of fatty liver and their contribution to the development of FLD. Methods: High-fat diet (HFD)-induced steatosis and methionine-choline-defident diet-induced steatohepatitis animal models were employed. Human serum samples were obtained from patients with FU) whose proton density fat fraction was estimated by magnetic resonance imaging. 3-Phosphoglycerate dehydrogenase (Phgdh)-knockout mouse embryonic fibroblasts (MEF) and transgenic mice overexpressing Phgdh (Tg-phgdh) were used to evaluate the role of serine metabolism in the development of FLD. Results: Expression of Phgdh was markedly reduced in the animal models. There were significant negative correlations of the serum serine with the liver fat fraction, serum alanine transaminase, and triglyceride levels among patients with FLD. Increased lipid accumulation and reduced NAD(+) and SIRT1 activity were observed in Phgdh-knockout MEF and primary hepatocytes incubated with free fatty adds; these effects were reversed by overexpression of Phgdh. Tg-Phgdh mice showed significantly reduced hepatic triglyceride accumulation compared with wild-type littermates fed a HID, which was accompanied by increased SIRT1 activity and reduced expression of lipogenic genes and proteins. Conclusions: Human and experimental data suggest that reduced Phgdh expression and serine levels are closely associated with the development of RD. (C) 2019 Elsevier Inc. All rights reserved.
URI
https://www.sciencedirect.com/science/article/pii/S002604951930215X?via%3Dihubhttps://repository.hanyang.ac.kr/handle/20.500.11754/155341
ISSN
0026-0495; 1532-8600
DOI
10.1016/j.metabol.2019.154000
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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