Pena Calderin Ernesto, Zheng Jing-Juan, Boyd Nolan L, Lynch Will, Sansbury Brian E, Spite Matthew, Hill Bradford G, Hellmann Jason
Center for Cardiometabolic Science, Christina Lee Brown Envirome Institute, Division of Environmental Medicine (E.P.C., J.-J.Z., N.L.B., W.L., B.E.S., B.G.H., J.H.), University of Louisville School of Medicine, KY.
Department of Physiology (E.P.C.), University of Louisville School of Medicine, KY.
Arterioscler Thromb Vasc Biol. 2025 Jul;45(7):1090-1110. doi: 10.1161/ATVBAHA.124.322234. Epub 2025 May 8.
Diet-induced white adipose tissue inflammation is associated with insulin resistance and metabolic perturbations. Conversely, exercise protects against the development of diet-induced chronic inflammation and insulin resistance independent of weight loss; however, the mechanisms remain largely unknown. We have recently shown that through adrenergic stimulation of macrophages, exercise promotes resolution of acute peritoneal inflammation by enhancing the biosynthesis of specialized proresolving lipid mediators. In this study, we sought to determine whether exercise stimulates proresolving pathways in adipose tissue and whether this response is modified by diet. Specifically, we hypothesized that exercise stimulates proresolving pathways by adrenergic signaling, which is inhibited by high-fat diet, priming the development of chronic inflammation in the adipose tissue.
To explore the dietary dependence of the proresolving effects of exercise, mice were fed either a control or high-fat diet for 2 weeks before, and throughout, a 4-week period of daily treadmill running. Glucose handling, body weight and composition, lipemia, and exercise performance were evaluated at the end of the feeding and exercise interventions. Likewise, changes in catecholamines and their biosynthetic enzymes were measured along with adipose tissue specialized proresolving lipid mediator levels and macrophage phenotype and abundance.
When compared with sedentary controls, macrophages isolated from mice exposed to 4 weeks of exercise display elevated expression of the specialized proresolving lipid mediator biosynthetic enzyme , while adipose tissue specialized proresolving lipid mediator levels and anti-inflammatory CD301 M2 macrophages increased. These changes were dependent upon diet as 6 weeks of feeding with high-fat diet abrogated the proresolving effect of exercise when compared with control diet-fed animals. Interestingly, exercise-induced epinephrine production was inhibited by high-fat diet, which diminished the expression of the epinephrine biosynthetic enzyme PNMT (phenylethanolamine N-methyltransferase) in adrenal glands.
Taken together, these results suggest that a diet high in fat diminishes the proresolving effects of exercise in the adipose tissue via decreasing the biosynthesis of catecholamines.
饮食诱导的白色脂肪组织炎症与胰岛素抵抗和代谢紊乱有关。相反，运动可预防饮食诱导的慢性炎症和胰岛素抵抗的发生，且与体重减轻无关；然而，其机制在很大程度上仍不清楚。我们最近发现，通过巨噬细胞的肾上腺素能刺激，运动可通过增强特异性促消退脂质介质的生物合成来促进急性腹膜炎症的消退。在本研究中，我们试图确定运动是否会刺激脂肪组织中的促消退途径，以及这种反应是否会受到饮食的影响。具体而言，我们假设运动通过肾上腺素能信号刺激促消退途径，而高脂饮食会抑制该信号，从而引发脂肪组织中慢性炎症的发展。
为了探究运动促消退作用对饮食的依赖性，在为期4周的每日跑步机跑步前及跑步期间，小鼠连续2周喂食对照饮食或高脂饮食。在喂食和运动干预结束时，评估葡萄糖处理能力、体重和组成、血脂以及运动表现。同样，测量儿茶酚胺及其生物合成酶的变化，以及脂肪组织特异性促消退脂质介质水平、巨噬细胞表型和丰度。
与久坐不动的对照组相比，从接受4周运动的小鼠中分离出的巨噬细胞显示，特异性促消退脂质介质生物合成酶的表达升高，而脂肪组织特异性促消退脂质介质水平和抗炎性CD301 M2巨噬细胞增加。这些变化取决于饮食，因为与喂食对照饮食的动物相比，高脂饮食喂养6周消除了运动的促消退作用。有趣的是，高脂饮食抑制了运动诱导的肾上腺素生成，这降低了肾上腺中肾上腺素生物合成酶PNMT（苯乙醇胺N-甲基转移酶）的表达。
综上所述，这些结果表明，高脂肪饮食通过减少儿茶酚胺的生物合成来减弱运动对脂肪组织的促消退作用。
