The combination of exercise and liraglutide synergistically enhanced metabolic insulin actions and reduced vascular oxidative stress and inflammation in rats with early diet-induced obesity.
Does the combination of liraglutide and exercise improve vascular and metabolic insulin actions in adult male rats with early diet-induced obesity?
Early combination of exercise and a GLP-1 receptor agonist synergistically prevents vascular and metabolic insulin resistance in a preclinical model of diet-induced obesity.
Inflammation-induced vascular insulin resistance is an early event in diet-induced obesity and contributes to metabolic insulin resistance. To examine whether exercise and glucagon-like peptide 1 (GLP-1) receptor agonism, alone or in combination, modulate vascular and metabolic insulin actions during obesity development, we performed a euglycemic insulin clamp in adult male rats after 2 weeks of high-fat diet feeding with either access to a running wheel (exercise), liraglutide, or both. Rats exhibited increased visceral adiposity and blunted microvascular and metabolic insulin responses. Exercise and liraglutide alone each improved muscle insulin sensitivity, but their combination fully restored insulin-mediated glucose disposal rates. The combined exercise and liraglutide intervention enhanced insulin-mediated muscle microvascular perfusion, reduced perivascular macrophage accumulation and superoxide production in the muscle, attenuated blood vessel inflammation, and improved endothelial function, along with increasing endothelial nucleus translocation of NRF2 and increasing endothelial AMPK phosphorylation. We conclude that exercise and liraglutide synergistically enhance the metabolic actions of insulin and reduce vascular oxidative stress and inflammation in the early stage of obesity development. Our data suggest that early combination use of exercise and GLP-1 receptor agonism might be an effective strategy in preventing vascular and metabolic insulin resistance and associated complications during the development of obesity. ARTICLE HIGHLIGHTS: Inflammation-induced vascular insulin resistance occurs early in diet-induced obesity and contributes to metabolic insulin resistance. We examined whether exercise and GLP-1 receptor agonism, alone or in combination, modulate vascular and metabolic insulin actions during obesity development. We found that exercise and liraglutide synergistically enhanced the metabolic actions of insulin and reduced perimicrovascular macrophage accumulation, vascular oxidative stress, and inflammation in the early stage of obesity development. Our data suggest that early combination use of exercise and a GLP-1 receptor agonist might be an effective strategy in preventing vascular and metabolic insulin resistance and associated complications during the development of obesity.
Liu et al. (Wed,) conducted a other in Early diet-induced obesity. Exercise, liraglutide, or both vs. High-fat diet alone was evaluated on Vascular and metabolic insulin actions (euglycemic insulin clamp). The combination of exercise and liraglutide synergistically enhanced metabolic insulin actions and reduced vascular oxidative stress and inflammation in rats with early diet-induced obesity.
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