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BRIEF RESEARCH REPORT article

Front. Pharmacol.
Sec. Neuropharmacology
Volume 15 - 2024 | doi: 10.3389/fphar.2024.1487585
This article is part of the Research Topic The Interplay Between GABA and Glutamate in Systems Physiology and Pathophysiology View all articles

Synergistic effects of peripheral GABA and GABA-transaminase inhibitory drugs on food intake control and weight loss in high-fat dietinduced obese mice

Provisionally accepted
Tomoka Nagao Tomoka Nagao 1Jason Braga Jason Braga 1,2Siyi Chen Siyi Chen 1Masubon Thongngam Masubon Thongngam 3Maesaya Chartkul Maesaya Chartkul 4Noriyuki Yanaka Noriyuki Yanaka 1Thanutchaporn Kumrungsee Thanutchaporn Kumrungsee 1*
  • 1 Hiroshima University, Hiroshima, Japan
  • 2 Cavite State University, Indang, Philippines
  • 3 Kasetsart University, Bangkok, Thailand
  • 4 Bangkok Chanthaburi Hospital, Chanthaburi, Thailand

The final, formatted version of the article will be published soon.

    Background: Developing anti-obesity interventions targeting appetite or food intake, the primary driver of obesity, remains challenging. Here, we demonstrated that dietary γ-aminobutyric acid (GABA) with GABA-degradation inhibitory drugs could be an anti-obesity intervention possessing strong food intake-suppressive and weight-loss effects.Methods: High-fat (HF)-diet-induced obese mice were divided into six groups receiving either the HF diet or the 2% GABA-HF diet with daily administration of PBS or the GABA-degradation inhibitory drugs, vigabatrin and ethanolamine-O-sulfate (EOS). In 24-h fast-induced refeeding, lean mice with a basal diet were used, and food intake was measured from 0.5 to 24 h after refeeding.Results: Coadministration of the 2% GABA-HF diet with vigabatrin or EOS significantly decreased food intake (-53%, -35%) and body weight (-22%, -16%) within 11 days in obese mice, along with a marked increase in plasma GABA levels. Mice receiving dietary GABA alone or the drugs alone exhibited no such effects. Hypothalamic GABA levels increased in drug-treated mice, regardless of diet. At 0.5 h after refeeding, food intake was similar in all groups. However, at 0.5 h, plasma GABA levels were markedly increased only in mice receiving coadministration of dietary GABA and the drugs, and their food intake was completely inhibited for over 6 h, while mice in other groups gradually increased their food intake. Conclusion: Combining dietary GABA with GABA-degradation inhibitory drugs effectively suppresses food intake and promotes weight loss in obese mice, primarily through increased plasma GABA availability. These findings may advance the development of food intake-controlling strategies for obesity management.

    Keywords: GABA, GABA-T, food intake, Obesity, Weight Loss, Semaglutide, Appetite, Vigabatrin

    Received: 28 Aug 2024; Accepted: 24 Sep 2024.

    Copyright: © 2024 Nagao, Braga, Chen, Thongngam, Chartkul, Yanaka and Kumrungsee. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Thanutchaporn Kumrungsee, Hiroshima University, Hiroshima, Japan

    Disclaimer: All claims expressed in this article are solely those of the authors and do not necessarily represent those of their affiliated organizations, or those of the publisher, the editors and the reviewers. Any product that may be evaluated in this article or claim that may be made by its manufacturer is not guaranteed or endorsed by the publisher.