Endocrine Abstracts

Exercise training and liraglutide have been shown to be effective in promoting weight loss, improving glycemic control, and regulating blood lipid levels, especially in animal models and patients with obesity and diabetes. However, their combined effects on body composition, glucose, and lipid metabolism in healthy aging models have not been studied yet. In this study, we used apparently healthy middle-aged (16-month-old) female Wistar rats that underwent ovariectomy (Ovx) to mimic human menopause. The Ovx was performed under isoflurane anesthesia (3%) with ketoprofen analgesia (5 mg/day). Two weeks after the surgery, the Ovx rats were randomly assigned to four groups: sedentary control (SC; received 0.3 ml/day normal saline subcutaneously), liraglutide (L; received 0.3ml Saxenda ®, Novo Nordisk A/S, Denmark, at a dose of 0.186 mg/kg body mass/day subcutaneously), exercise strength-endurance training (E; ladder-climbing with 25-50% body weight load 3 times/week), and liraglutide + exercise (L+E) groups. The treatment lasted for seven weeks, with an additional two weeks of adaptation to exercise or liraglutide treatment. Compared to the sedentary control group, the L+E group showed the most significant weight loss (P<0.05) and reduction in relative retroperitoneal adipose tissue weight (g/100g body mass). The relative weight of the slow-twitch soleus muscle increased (P<0.05) in the L+E group, while the relative weight of the mixed (fast/slow)-twitch gastrocnemius muscle remained unchanged. The serum glucose area under the curve (AUC) following the intraperitoneal glucose tolerance test was lower only in the E group. Conversely, liraglutide treatment mainly contributed to the reduction of total cholesterol, triglycerides, and non-high density lipoprotein (HDL) concentrations in serum compared to exercise alone, which was similar to the effects of the combined E + L treatment. Our findings suggest that in apparently healthy middle-aged Ovx rats, the combination of liraglutide treatment and exercise had the most significant synergistic effects on weight loss, reduction of adipose tissue, soleus muscle activation and improvement in body composition. The improved lipid profiles were mainly due to liraglutide treatment, while exercise alone enhanced glycemic control, indicating their diverse impacts on metabolic parameters in this model.