Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice

Chen, Sing-Young and Telfser, Aiden J. and Olzomer, Ellen M. and Vancuylenberg, Calum S. and Zhou, Mingyan and Beretta, Martina and Li, Catherine and Alexopoulos, Stephanie J. and Turner, Nigel and Byrne, Frances L. and Santos, Webster L. and Hoehn, Kyle L. (2024) Beneficial effects of simultaneously targeting calorie intake and calorie efficiency in diet-induced obese mice. Clinical Science, 138 (4). pp.173-187. ISSN 0143-5221

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Link to published document: http://doi.org/10.1042/CS20231016

Abstract

Semaglutide is an anti-diabetes and weight loss drug that decreases food intake, slows gastric emptying, and increases insulin secretion. Patients begin treatment with low-dose semaglutide and increase dosage over time as efficacy plateaus. With increasing dosage, there is also greater incidence of gastrointestinal side effects. One reason for the plateau in semaglutide efficacy despite continued low food intake is due to compensatory actions whereby the body becomes more metabolically efficient to defend against further weight loss. Mitochondrial uncoupler drugs decrease metabolic efficiency, therefore we sought to investigate the combination therapy of semaglutide with the mitochondrial uncoupler BAM15 in diet-induced obese mice. Mice were fed high-fat western diet (WD) and stratified into six treatment groups including WD control, BAM15, low-dose semaglutide without or with BAM15, and high-dose semaglutide without or with BAM15. Combining BAM15 with either semaglutide dose decreased body fat and liver triglycerides, which was not achieved by any monotherapy, while high-dose semaglutide with BAM15 had the greatest effect on glucose homeostasis. This study demonstrates a novel approach to improve weight loss without loss of lean mass and improve glucose control by simultaneously targeting energy intake and energy efficiency. Such a combination may decrease the need for semaglutide dose escalation and hence minimize potential gastrointestinal side effects.

Item Type: Article
Subjects: R Medicine > R Medicine (General)
Depositing User: Repository Administrator
Date Deposited: 14 Dec 2024 01:34
Last Modified: 14 Dec 2024 01:34
URI: https://eprints.victorchang.edu.au/id/eprint/1506

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