3,5-Dimethyl-2,4,6-trimethoxychalcone Lessens Obesity and MAFLD in Leptin-Deficient ob/ob Mice

• Published in: International journal of molecular sciences Vol. 25; no. 18; p. 9838
• Main Authors: Gaigé, Stéphanie, Abysique, Anne, Barbouche, Rym, Tonetto, Alain, Di Maio, Attilio, Robin, Maxime, Lormier, Anh-Tuan, Troadec, Jean-Denis
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 11.09.2024; MDPI
• Subjects: Animals; Anti-Obesity Agents - chemistry; Anti-Obesity Agents - pharmacology; Body mass index; Causes of; Chalcones - chemistry; Chalcones - pharmacology; Development and progression; Diet therapy; Eating - drug effects; Fatty acids; Fatty liver; Food; Glucose; Health aspects; Hypothalamus; Leptin; Leptin - metabolism; Life Sciences; Liver - drug effects; Liver - metabolism; Liver diseases; Male; Metabolism; Mice; Mice, Inbred C57BL; Mice, Obese; Mutation; Obesity; Obesity - drug therapy; Obesity - metabolism; Overweight; Physiological aspects; Polyphenols; Public health; France; chalcone; liver; brainstem; leptin; steatosis; hypothalamus; food intake
• ISSN: 1422-0067; 1661-6596; 1422-0067
• DOI: 10.3390/ijms25189838

Chalcones constitute an important group of natural compounds abundant in fruits and comestible plants. They are a subject of increasing interest because of their biological activities, including anti-diabetic and anti-obesity effects. The simple chalcone structural scaffold can be modified at multiple sites with different chemical moieties. Here, we generated an artificial chalcone, i.e., 3,5-dimethyl-2,4,6-trimethoxychalcone (TriMetChalc), derived from 2′,4′-Dihydroxy-6′-methoxy-3′,5′-dimethylchalcone (DMC). DMC is a major compound of Cleistocalyx operculatus, a plant widely used in Asia for its anti-hyperglycemic activity. Using ob/ob mice as an obesity model, we report that, after 3 weeks of per os administration, TriMetChalc modified food intake through the specific activation of brain structures dedicated to the regulation of energy balance. TriMetChalc also decreased weight gain, glucose intolerance, and hepatic steatosis. Moreover, through extensive liver lipidomic analysis, we identified TriMetChalc-induced modifications that could contribute to improving the liver status of the animals. Hence, TriMetChalc is a chalcone derivative capable of reducing food intake and the addition of glucose intolerance and hepatic steatosis in a mouse model of obesity. In light of these results, we believe that TriMetChalc action deserves to be more deeply evaluated over longer treatment periods and/or in combination with other chalcones with protective effects on the liver.