OBJECTIVE: To compare the effects of diet restriction and semaglutide treatment on body composition (BC), energy expenditure (EE), and metabolic adaptation (MA) in Göttingen Minipigs as a model for human obesity.
METHODS: Diet-induced obese Göttingen Minipigs were divided into three groups (n=8): a control group receiving vehicle and fed, a group treated with the GLP-1 receptor agonist (GLP-1RA) semaglutide and fed, and a diet-restricted group receiving vehicle and weight-matched the semaglutide group. BC, EE, and plasma parameters were measured at baseline and after 10 weeks; tissue mitochondrial respiration and myosin conformation were measured after 10 weeks. ad libitum ad libitum
RESULTS: Diet-restricted minipigs gained 6.8 % (p<0.01) more body fat compared to semaglutide, mediated by a greater loss of fat-free mass (4.3 kg, p<0.05) and a tendency for a higher fat mass gain (p=ns). Diet restriction led to significantly decreased EE compared to the control group (-273 kcal/day, p<0.05), but no differences between groups were observed when adjusting EE for changes in BC. Energy balance modeling revealed significant MA in the diet-restricted animals (p<0.01) compared to both control and semaglutide groups. Diet restriction was further associated with decreased proton leak and resting myosin ATP consumption in muscle.
CONCLUSIONS: Semaglutide treatment improved BC and EE outcomes compared to diet restriction despite similar weight trajectories. Furthermore, semaglutide treatment prevented specific energy-conserving changes in tissues, thus highlighting novel mechanisms regulating energy balance during GLP-1RA treatment.
