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Menthol to Induce Non-shivering Thermogenesis via TRPM8/PKA Signaling for Treatment of Obesity

Journal of Obesity & Metabolic Syndrome 2021년 30권 1호 p.4 ~ 11
Sanders Owen Davis, Rajagopal Jayalekshmi Archa, Rajagopal Lekshmy,
소속 상세정보
 ( Sanders Owen Davis ) - Portland State University Department of Biology
 ( Rajagopal Jayalekshmi Archa ) - Dr. D. Y. Patil Medical College Department of Pathology
 ( Rajagopal Lekshmy ) - College of Physicians and Surgeons Oto-Rhino-Laryngology

Abstract


Increasing basal energy expenditure via uncoupling protein 1 (UCP1)-dependent non-shivering thermogenesis is an attractive therapeutic strategy for treatment of obesity. Transient receptor potential melastatin 8 (TRPM8) channel activation by cold and cold mimetics induces UCP1 transcription and prevents obesity in animals, but the clinical relevance of this relationship remains incompletely understood. A review of TRPM8 channel agonism for treatment of obesity focusing on menthol was undertaken. Adipocyte TRPM8 activation results in Ca2+ influx and protein kinase A (PKA) activation, which induces mitochondrial elongation, mitochondrial localization to lipid droplets, lipolysis, β-oxidation, and UCP1 expression. Ca2+-induced mitochondrial reactive oxygen species activate UCP1. In animals, TRPM8 agonism increases basal metabolic rate, non-shivering thermogenesis, oxygen consumption, exercise endurance, and fatty acid oxidation and decreases abdominal fat percentage. Menthol prevents high-fat diet-induced obesity, glucose intolerance, insulin resistance, and liver triacylglycerol accumulation. Hypothalamic TRPM8 activation releases glucagon, which activates PKA and promotes catabolism. TRPM8 polymorphisms are associated with obesity. In humans, oral menthol and other TRPM8 agonists have little effect. However, topical menthol appears to increase core body temperature and metabolic rate. A randomized clinical control trial of topical menthol in obese patients is warranted.

키워드

Obesity; Weight loss; Mitochondrial uncoupling proteins; Brown adipose tissue; Thermogenesis

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