Anti-obesity function by hypothalamic neurons projecting brainstem

2022 Fiscal Year Final Research Report

• Project/Area Number: 21K15206
• Research Category: Grant-in-Aid for Early-Career Scientists
• Allocation Type: Multi-year Fund
• Review Section: Basic Section 46030:Function of nervous system-related
• Research Institution: Hokkaido University
• Principal Investigator: Izawa Shuntaro 北海道大学, 獣医学研究院, 特別研究員(PD) (30897632)
• Project Period (FY): 2021-04-01 – 2023-03-31
• Keywords: 視床下部 / 抗肥満 / 代謝 / MCH

Outline of Final Research Achievements

Hypothalamic melanin-concentrating hormone (MCH) peptide robustly affects energy homeostasis. However, it is unclear whether and how MCH-producing neurons, which contain and release a variety of neuropeptides/transmitters, regulate energy expenditure in the central nervous system and peripheral tissues. We thus examined the regulation of energy expenditure by MCHneurons, focusing on interscapular brown adipose tissue (BAT) activity. MCH neuron-ablated mice exhibited reduced body weight, increased oxygen consumption, and increased BAT activity, which improved locomotor activity-independent energy expenditure. The medullary raphe nucleus (MRN) neurons were activated by MCHneuron ablation. Therefore, endogenous MCHneuron activity negatively modulates energy expenditure via BAT inhibition. MRN neurons might receive inhibitory input from MCH neurons to suppress BAT activity.

Free Research Field

神経科学

Academic Significance and Societal Importance of the Research Achievements

MCH受容体アンタゴニストは抗肥満薬としての可能性が複数の製薬会社から検証され、臨床試験においても効果が確認されている。しかし、抗肥満を誘導する神経メカニズムは不明で、また、悪夢や頻脈といった副作用から現在まで実用化には至っていない。本研究によりMCH神経がエネルギー消費節約に機能する神経回路が明らかになったことで、延髄縫線核をターゲットとし代謝に焦点を定めたMCHブロッカーの道が開ける可能性がある。