Alternate-Day Modified Fasting Shifts Metabolically Unhealthy Obesity to Metabolically Healthy Obesity in Obese Rats

Alternate-day fasting is an emerging strategy for caloric restriction and treatment of obesity. We aimed to assess the effects of alternate-day modified fasting (ADMF) on adipose tissue dysfunction and hepatic insulin signaling pathway, inflammation, and oxidative stress in diet-induced obesity rats. Wistar male rats (n=18) were divided equally into three groups: control (regular chow), high-fat diet (HFD), and HFD+ADMF groups. Animals underwent assessments of weekly body weight, glucose tolerance tests, serum biochemical markers, and adiponectin, insulin, and leptin were assessed. Hepatic tissue was assessed for 1) insulin receptors and insulin signaling pathway, 2) inflammatory and oxidative profiles, and 3) histopathological changes, and pancreatic tissue was assessed for histopathological changes. In HFD-fed animals, ADMF decreased body weight and improved glucose tolerance. ADMF restored hepatic and adipose tissue insulin sensitivity and ameliorated inflammatory and oxidative stress profiles and histopathological changes in hepatic tissue. ADMF also restored the normal function of adipose tissue. In conclusion, ADMF changes metabolically unhealthy obesity to metabolically healthy obesity despite maintaining a high-fat diet feeding in rats through improving adipose tissue dysfunction and modulation of the hepatic insulin signaling pathway, inflammation, and oxidative stress.

隔日禁食是一种新兴的热量限制与肥胖治疗策略。本研究旨在评估改良型隔日禁食（alternate-day modified fasting, ADMF）对饮食诱导肥胖大鼠脂肪组织功能障碍、肝脏胰岛素信号通路、炎症反应及氧化应激的影响。我们将18只雄性Wistar大鼠随机均分为3组：对照组（普通饲料喂养）、高脂饮食（high-fat diet, HFD）组及HFD+ADMF组。对所有大鼠开展每周体重监测、葡萄糖耐量试验，并检测血清生化指标以及脂联素、胰岛素与瘦素水平。分别对肝组织进行以下3项检测：1）胰岛素受体及胰岛素信号通路情况；2）炎症与氧化应激状态；3）组织病理学变化；同时对胰腺组织进行病理学检查。研究结果显示，在高脂饮食喂养的大鼠中，ADMF可降低体重并改善葡萄糖耐量。ADMF能够恢复肝组织与脂肪组织的胰岛素敏感性，改善肝组织的炎症、氧化应激状态及病理学变化，同时还可恢复脂肪组织的正常功能。综上，尽管大鼠仍维持高脂饮食喂养，ADMF可通过改善脂肪组织功能障碍、调节肝脏胰岛素信号通路、炎症反应及氧化应激，将代谢不健康肥胖转化为代谢健康肥胖。