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

TY - JOUR

T1 - Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice

AU - Chen, Sing-Young

AU - Beretta, Martina

AU - Olzomer, Ellen M.

AU - Alexopoulos, Stephanie J.

AU - Shah, Divya P.

AU - Byrne, Frances L.

AU - Salamoun, Joseph M.

AU - Garcia, Christopher J.

AU - Smith, Greg C.

AU - Larance, Mark

AU - Philp, Andrew

AU - Turner, Nigel

AU - Santos, Webster L.

AU - Cantley, James

AU - Hoehn, Kyle L.

N1 - Copyright:© 2023 The Authors. Published by Elsevier B.V.

PY - 2024/1

Y1 - 2024/1

N2 - 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.

AB - 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.

KW - Mitochondrial uncoupling

KW - Diabetes

KW - Obesity

KW - GLP-1

KW - Calorie restriction

UR - https://www.scopus.com/pages/publications/85172989886

U2 - 10.1016/j.bbadis.2023.166908

DO - 10.1016/j.bbadis.2023.166908

M3 - Article

C2 - 37793464

SN - 0925-4439

VL - 1870

JO - BBA - Molecular Basis of Disease

JF - BBA - Molecular Basis of Disease

IS - 1

M1 - 166908

ER -