Abnormal energy metabolism induced by hypothalamic low-graded inflammation

2017 Fiscal Year Final Research Report

• Project/Area Number: 15K07442
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Food science
• Research Institution: Tokyo University of Pharmacy and Life Science
• Principal Investigator: TAKAHASHI Yuji 東京薬科大学, 生命科学部, 教授 (20154875)
• Project Period (FY): 2015-04-01 – 2018-03-31
• Keywords: ストレス応答 / 視床下部 / 肥満 / 転写因子 / 代謝異常 / 内分泌撹乱化学物質 / 遺伝子欠損マウス

Outline of Final Research Achievements

This research was planned to clarify how stress responsive transcription factor ATF5 could participate in energy metabolism abnormality due to low-graded inflammation of the hypothalamus using ATF5-deffective mouse and hypothalamic immortalized cells. It was demonstrated that ATF5 was induced by endoplasmic reticulum stress detected in the hypothalamus because of obesity, and that ATF5 also mediated signals associating with ER-stress initiated mitochondrial stress from the mitochondria to the nucleus. ATF5-knockout mice demonstrated the low body-weight both in a normal meal feeding and in the high-fat meal feeding. In addition, exposure of hypothalamus cells to tributyltin, an endocrine-disrupting chemical, caused an inflammatory response leading to mitochondrial fragmentation and the repression of the appetite inhibitor α MSH. These results suggest that ATF5 could play an important role in low-graded inflammation and the obese development through the hypothalamus malfunction.

Free Research Field

環境分子生理学