Mechanism of PHLDB1-mediated glycolipid metabolism and adipokine secretion in adipocytes

2022 Fiscal Year Final Research Report

• Project/Area Number: 20K08883
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Review Section: Basic Section 54040:Metabolism and endocrinology-related
• Research Institution: University of Yamanashi
• Principal Investigator: Tsuchiya Kyoichiro 山梨大学, 大学院総合研究部, 教授 (60451936)
• Project Period (FY): 2020-04-01 – 2023-03-31
• Keywords: インスリン抵抗性

Outline of Final Research Achievements

In wild-type mice, PHLDB1 protein was lowly expressed in skeletal muscle and liver and highly expressed in the adipocyte fraction of adipose tissue (periventricular and subcutaneous). PHLDB1 protein expression was decreased in adipose tissue of high-fat diet-induced obese mice. Systemic PHLDB1 knock-in mice had enhanced Akt phosphorylation in adipose tissue and not in liver after insulin administration compared to wild-type mice. Normal- and high-fat diet-loaded systemic PHLDB1 knock-in mice had improved glucose intolerance and insulin resistance without increased body weight and liver fat accumulation compared to control wild-type mice. Furthermore, similar phenotypes were observed in adipocyte-specific PHLDB1 knock-in mice.

Free Research Field

内分泌・代謝学

Academic Significance and Societal Importance of the Research Achievements

脂肪細胞における微小管捕捉因子の生理的意義は未知であり、糖脂質代謝のみならず、PHLDB1の細胞生物学的な意義を有すると考えられる。加えて、糖脂質代謝の改善を目的とした薬理学的手法による臓器選択的な分子制御を考慮する際にも、標的とする病態に関連する分子の臓器間差異に着目してアプローチする本研究手法は臨床医学的な意義も有すると考えられる。