Exercise training cycles persistently improve glucose homeostasis and alters hepatic fatty acid oxidation

Abstract

Obesity is a metabolic disease associated with a lower capacity for fatty acid oxidation (FAO) that contributes to insulin resistance and reduces metabolic fuel flexibility. Conversely, the long-term consequences of obesity can be reversed through exercise training. While studies suggest that exercise elicits long-lasting and persistent adaptations in muscle akin to an “exercise memory”, how a hepatic memory is established remains unknown. This is key given that beneficial adaptations to the exercised muscle cannot occur without support from the liver. Thus, we hypothesize that exercise training elicits a hepatic “exercise memory” that persists after exercise cessation and is accentuated by retaining to improve metabolic health and FAO. Here, we used male SEDentary (static cages; SED) and exercise-TRAINed (wheel running, TRAIN) chow-fed mice and investigated how exercise impacts whole body glucose homeostasis (glucose tolerance test [GTT], insulin tolerance test [ITT], pyruvate tolerance test [PTT]) and hepatic FAO following training (4wks), detraining (8wk), and retraining (12wk) in three independent cohorts. Exercise training reduced adiposity ( p<0.01) and improved glucose tolerance (GTT) ( p<0.05), compared to SED. Metabolic improvements in TRAIN mice were accompanied by higher gene expression of FAO enzyme Hadha ( p<0.05). Further, improvements to adiposity and glucose handling disappear after detraining. Nevertheless, after detraining, TRAIN mice had a higher expression of lipid uptake ( Lpl, p<0.05), mitochondrial function ( Sdha, Sdhb, p< 0.05), and FAO genes ( Acadvl, p=0.053). Following retraining, we observed a significant enhancement of basal glucose ( p<0.05) and a main effect of exercise training on glucose homeostasis (GTT, ITT, PTT) across timepoints (factorial ANOVA p< 0.001). However, mitochondrial and FAO gene expression ( Sdha, Sdhb, p<0.05, Acadvl, p=0.053) were reduced with retraining in TRAIN mice, compared to SED. In conclusion, we observed that exercise training improves glucose homeostasis, which is further potentiated through exercise retraining. This effect was accompanied by dynamic changes in expression of genes related to mitochondrial function, FAO, and lipid uptake. Our data may suggest a dynamic reprogramming of hepatic fatty acid handling with training, that may persist with detraining, and can be enhanced with retraining. Funding was provided by the University of Illinois Urbana-Champaign. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.