Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice.

Metabolic disorders such as type 2 diabetes, fatty liver disease, hyperlipidemia, and obesity commonly co-occur but clinical treatment options do not effectively target all disorders. Calorie restriction, semaglutide, rosiglitazone, and mitochondrial uncouplers have all demonstrated efficacy against one or more obesity-related metabolic disorders, but it currently remains unclear which therapeutic strategy best targets the combination of hyperglycaemia, liver fat, hypertriglyceridemia, and adiposity. Herein we performed a head-to-head comparison of 5 treatment interventions in the female db/db mouse model of severe metabolic disease. Treatments included ∼60 % calorie restriction (CR), semaglutide, rosiglitazone, BAM15, and niclosamide ethanolamine (NEN). Results showed that BAM15 and CR improved body weight and liver steatosis to levels superior to semaglutide, NEN, and rosiglitazone, while BAM15, semaglutide, and rosiglitazone improved glucose tolerance better than CR and NEN. BAM15, CR, semaglutide, and rosiglitazone all had efficacy against hypertriglyceridaemia. These data provide a comprehensive head-to-head comparison of several key treatment strategies for metabolic disease and highlight the efficacy of mitochondrial uncoupling to correct multiple facets of the metabolic disease milieu in female db/db mice.
Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Kyle Hoehn reports financial support was provided by National Institutes of Health and National Health and Medical Research Council. Kyle Hoehn reports a relationship with Uncoupler Therapeutics, Inc. that includes: board membership and equity or stocks. Kyle Hoehn reports a relationship with Life Biosciences, Inc. that includes: equity or stocks. Kyle Hoehn has a patent via University of Virginia. Webster Santos reports financial support was provided by National Institutes of Health. Webster Santos reports a relationship with Uncoupler Therapeutics, Inc. that includes: board membership and equity or stocks. Webster Santos reports a relationship with Life Biosciences, Inc. that includes: equity or stocks.
(Copyright © 2023 The Authors. Published by Elsevier B.V. All rights reserved.)