The mechanism of high fat diet induced neural inflammation and obese

2018 Fiscal Year Final Research Report

• Project/Area Number: 16K09761
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Metabolomics
• Research Institution: University of Miyazaki
• Principal Investigator: Sakoda Hideyuki 宮崎大学, 医学部, 講師 (50376464)
• Project Period (FY): 2016-04-01 – 2019-03-31
• Keywords: グレリン / 肥満 / 摂食中枢 / 自律神経 / 炎症

Outline of Final Research Achievements

In mice, ghrelin’s orexigenic activity was abolished after 2-4 weeks HFD, consistent with the timing of accumulation and activation of macrophages and microglia in the nodose ganglion and hypothalamus. Calorie-restricted weight loss restored ghrelin responsiveness and alleviated the upregulation of macrophage/microglia activation markers and inflammatory cytokines.
Aged mice easily gained weight during short-term HFD feeding, and required many days to adapt their energy intake. One-day HFD in aged mice induced inflammation in the distal colon, but not in the nodose ganglion or hypothalamus. The anorexic effect of GLP-1 was attenuated in aged mice. mRNA expression of the gene encoding the GLP-1 receptor in the nodose ganglion was significantly lower in aged mice than in young mice. These findings suggest that adaptation of energy intake regulation was attenuated in aged mice, causing them to become obese in response to short-term HFD feeding.

Free Research Field

糖尿病

Academic Significance and Societal Importance of the Research Achievements

過栄養や糖代謝異常による慢性炎症が、迷走神経節や視床下部にも及び、ペプチド受容体の発現低下から摂食行動の異常に至る分子機序を明らかにした。加齢によって自律神経を介する摂食調節機構が減弱し高脂肪食による肥満を生じやすくなる可能性が示唆された。