Deletion of PHGDH in adipocytes improves glucose intolerance in diet-induced obese mice

Journal Article · Sat Sep 15 04:00:00 EDT 2018 · Biochemical and Biophysical Research Communications

DOI:https://doi.org/10.1016/J.BBRC.2018.08.180· OSTI ID:23134227

Okabe, Keisuke ^[1]; Usui, Isao ^[2]; Yaku, Keisuke ^[1]; Hirabayashi, Yoshio ^[3]; Tobe, Kazuyuki ^[2]; Nakagawa, Takashi ^[1]

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1. Department of Metabolism and Nutrition, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, 930-0194 (Japan)
2. First Department of Internal Medicine, Graduate School of Medicine and Pharmaceutical Science for Research, University of Toyama, Toyama, 930-0194 (Japan)
3. Neuronal Circuit Mechanisms Research Group, RIKEN Brain Science Institute, Saitama, 351-0198 (Japan)

Highlights: • PHGDH is abundantly expressed in mature adipocytes of white adipose tissue. • Adipocyte-specific PHGDH KO mice exhibit normal adipose tissue development. • Adipocyte-specific PHGDH KO mice exhibit improved glucose tolerance upon obesity. • Serine-deficient diet feeding also exhibits favorable effects on glucose metabolism. Serine is a nonessential amino acid and plays an important role in cellular metabolism. In mammalian serine biosynthesis, 3-phosphoglycerate dehydrogenase (PHGDH) is considered a rate-limiting enzyme and is required for normal development. Although the biological functions of PHGHD in the nervous system have been intensively studied, its function in adipose tissue is unknown. In this study, we found that PHGDH is abundantly expressed in mature adipocytes of white adipose tissue. We generated an adipocyte-specific PHGDH knockout mouse (PHGDH FKO) and used it to investigate the role of serine biosynthesis in adipose tissues. Although PHGDH FKO mice had no apparent defects in adipose tissue development, these mice ameliorated glucose intolerance upon diet-induced obesity. Additionally, we found that the serine levels increase drastically in the adipose tissues of obese wild type mice, whereas no significant rise was observed in PHGDH FKO mice. Furthermore, wild type mice fed a serine-deficient diet also exhibited better glucose tolerance. These results suggest that PHGDH-mediated serine biosynthesis has important roles in adipose tissue glucose metabolism and could be a therapeutic target for diabetes in humans.

• OSTI ID: 23134227
• Journal Information: Biochemical and Biophysical Research Communications, Journal Name: Biochemical and Biophysical Research Communications Journal Issue: 1 Vol. 504; ISSN 0006-291X; ISSN BBRCA9
• Country of Publication: United States
• Language: English

Related Subjects

60 APPLIED LIFE SCIENCES
ADIPOSE TISSUE
BIOSYNTHESIS
GLUCOSE
METABOLIC DISEASES
METABOLISM
MICE
NERVOUS SYSTEM
OXIDOREDUCTASES
SERINE