Abstract：
Obesity is caused by an imbalance between energy intake and energy expenditure. This study aimed to determine the effects and mechanisms of 2\',4\'-dihydroxy-6\'-methoxy-3\',5\'-dimethylchalcone (DMC) on exercise tolerance in high-fat diet (HFD)-fed mice. Male C57BL/6J mice were randomly divided into two categories (7 groups [n = 8]): sedentary (control [CON], HFD, 200 mg/kg DMC, and 500 mg/kg DMC) and swimming (HFD, 200 mg/kg DMC, and 500 mg/kg DMC). Except the CON group, all other groups were fed HFD with or without DMC intervention for 33 days. The swimming groups were subjected to exhaustive swimming (three sessions/week). Changes in swimming time, glucolipid metabolism, body composition, biochemical indicators, histopathology, inflammation, metabolic mediators, and protein expression were assessed. DMC combined with regular exercise improved endurance performance, body composition, glucose and insulin tolerance, lipid profile, and the inflammatory state in a dose-dependent manner. Further, DMC alone or combined with exercise could restore normal tissue morphology, reduce fatigue-associated markers, and boost whole-body metabolism and the protein expression of phospho-AMP-activated protein kinase alpha/total-AMP-activated protein kinase alpha (AMPK), sirtuin-1 (SIRT1), peroxisome-proliferator-activated receptor gamma coactivator 1alpha (PGC-1α), and peroxisome proliferator-activated receptor alpha in the muscle and adipose tissues of HFD-fed mice. DMC exhibits antifatigue effects by regulating glucolipid catabolism, inflammation, and energy homeostasis. Furthermore, DMC exerts a synergistic exercise-related metabolic effect via the AMPK-SIRT1-PGC-1α signaling pathway, suggesting that DMC is a potential natural sports supplement with mimicked or augmented exercise effects for obesity prevention.
摘要：
肥胖是由能量摄入和能量消耗之间的不平衡引起的。本研究旨在确定2'的作用和机制，4\'-二羟基-6\'-甲氧基-3\'，5'-二甲基查耳酮（DMC）对高脂饮食（HFD）喂养小鼠运动耐量的影响。雄性C57BL/6J小鼠随机分为两类（7组[n=8]）：久坐（对照[CON]，HFD,200mg/kgDMC，和500毫克/千克DMC）和游泳（HFD，200mg/kgDMC，和500mg/kgDMC)。除了CON组,所有其他组接受有或无DMC干预的HFD喂养33天.游泳组进行力竭游泳（三个疗程/周）。游泳时间的变化，糖脂代谢，身体成分,生化指标,组织病理学,炎症,代谢介质，和蛋白质表达进行评估。DMC结合定期锻炼提高耐力表现，身体成分,葡萄糖和胰岛素耐量，血脂谱,和炎症状态呈剂量依赖性。Further,DMC单独或联合运动可恢复正常组织形态，减少疲劳相关标记，并促进全身代谢和磷酸化AMP激活的蛋白激酶α/总AMP激活的蛋白激酶α（AMPK）的蛋白表达，sirtuin-1(SIRT1)，过氧化物酶体增殖物激活受体γ辅激活因子1α（PGC-1α），HFD喂养小鼠的肌肉和脂肪组织中的过氧化物酶体增殖物激活受体α。DMC通过调节糖脂分解代谢表现出抗疲劳作用，炎症,和能量稳态。此外，DMC通过AMPK-SIRT1-PGC-1α信号通路发挥协同运动相关代谢作用,这表明DMC是一种潜在的天然运动补充剂，具有模仿或增强的运动效果，可预防肥胖。
