ArticleDiabetes, obesity & metabolism2026
Exercise Resistance in Obese Male NZO Mice Manifests as Local Muscle Remodelling Without Glycaemic Improvements.
Article in Diabetes, obesity & metabolism, 2026. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 1 paper.
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1 citing paper in PubMed.
- Exercise Resistance in Obese Male NZO Mice Manifests as Local Muscle Remodelling Without Glycaemic Improvements.Diabetes, obesity & metabolism · 2026Article
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19 authors.
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Abstract
aimsExercise improves glycaemic control, yet some individuals show limited benefit, termed exercise resistance. We investigated tissue-specific adaptations to chronic exercise in a polygenic model of obesity-driven type 2 diabetes (T2D). MATERIALS AND
methodsMale New Zealand Obese (NZO) mice were fed a high-fat diet and underwent 6 weeks of interval treadmill training. Physical capacity, body composition, glucose metabolism, skeletal muscle and liver glycogen and triglycerides, mitochondrial function, transcriptomics and systemic metabolites were assessed.
resultsThe training regime had a positive impact on several physiological parameters, including increased physical capacity (18%, p < 0.01), skeletal muscle AMPK phosphorylation (25%, p < 0.05), complex I-linked respiration (67%, p < 0.05) and transcriptomic enrichment of muscle contraction pathways in trained versus sedentary NZO mice. However, body weight, fat mass, fasting glycaemia, insulin-stimulated glucose uptake, AKT phosphorylation and GLUT4 abundance remained unaltered. Plasma branched-chain amino acids (BCAAs) and ketone bodies (3.3-fold higher in trained, p < 0.05) increased, hepatic triglycerides rose (25%, p < 0.001) with hepatic glycogen depletion (37%, p < 0.05) and caloric intake was slightly higher.
conclusionsInterval training induced muscle-specific remodelling and enhanced physical capacity without improving systemic insulin sensitivity. Persistent adiposity, exacerbated hepatic steatosis and elevated circulating BCAAs may contribute to limited glycaemic improvement, with altered energy balance as a possible confounder. Consequently, the NZO model offers translational insight into tissue-uncoupled exercise resistance observed in human polygenic obesity and T2D heterogeneity.
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