Study summary · research use only
Head-to-head comparison of BAM15, semaglutide, rosiglitazone, NEN, and calorie restriction on metabolic physiology in female db/db mice
Plain-language summary
Paraphrased from the published abstract below — not a verdict on whether anything works.
This study used female db/db mice, a rodent model of severe metabolic disease, to compare calorie restriction (CR), semaglutide, rosiglitazone, BAM15, and niclosamide ethanolamine (NEN) across measures of hyperglycaemia, liver fat, hypertriglyceridemia, and adiposity. BAM15 and CR were associated with greater improvements in body weight and liver steatosis compared with semaglutide, NEN, and rosiglitazone, while BAM15, semaglutide, and rosiglitazone were associated with greater improvement in glucose tolerance than CR and NEN. BAM15, CR, semaglutide, and rosiglitazone were all associated with reduced hypertriglyceridaemia. The authors describe this as a comprehensive head-to-head comparison of treatment strategies for metabolic disease in this mouse model, highlighting mitochondrial uncoupling as one approach addressing multiple aspects of metabolic disease.
Abstract
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.
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