Obesity is critically related with the development of metabolic and pathophysiological alterations among which non-alcoholic fatty liver disease (NAFLD) is of especial relevance. Although there are numerous strategies to successfully treat obesity, the prevention of weight regain still remains challenging for individuals who have undergone weight loss programs. In such context, diet and physical activity are considered essential for the regulation of body weight and lipid metabolism. In this study, rats were fed a high-fat diet (HFD) to induce obesity and alterations in hepatic lipid metabolism. Obese rats were then treated with single or combined strategies of caloric restriction, physical exercise, and/or pharmacological treatment with an appetite suppressant, to lose weight, reverse the obesity-related alterations in hepatic morphology and lipid metabolism and maintain the beneficial effects of the interventions used. HFD induced excess body weight, hepatic steatosis, altered fatty acid profile, dysregulated gene expression of lipogenic and lipolytic enzymes, as well as plasma markers of liver damage, and modifications in liver antioxidant enzyme activity. Such alterations were ameliorated by caloric restriction in combination with a mixed training protocol and/or food-intake inhibitor administration during a weight loss intervention period of 3 weeks, and the beneficial effects remained after 6 weeks of weight maintenance, with some interesting interactions observed. In conclusion, weight loss strategies assayed were efficient at correcting the obesogenic action of a HFD and related alterations in hepatic functionality through different molecular mechanisms. The beneficial effects were also evident along the post-intervention maintenance period to avoid body weight regain.

肥胖与代谢和病理生理变化的发展至关重要，其中非酒精性脂肪性肝病（NAFLD）特别相关。尽管有许多成功治疗肥胖症的策略，但是对于已经进行了减肥计划的个人而言，如何防止体重恢复仍然是一项挑战。在这种情况下，饮食和体育活动被认为对调节体重和脂质代谢至关重要。在这项研究中，给大鼠喂食高脂饮食（HFD）以诱导肥胖症和肝脂质代谢改变。然后，对肥胖大鼠进行热量限制，体育锻炼和/或使用食欲抑制剂进行药物治疗的单一或联合策略，以减轻体重，逆转肥胖相关的肝形态和脂质代谢变化，并保持所用干预措施的有益效果。HFD会导致体重过重，肝脂肪变性，改变的脂肪酸谱，生脂酶和脂解酶的基因表达失调以及肝损伤的血浆标志物以及肝抗氧化酶活性的改变。在三周的减肥干预期间，通过热量限制与混合训练方案和/或食物摄入抑制剂的给药相结合，可以改善这种改变，并且在维持体重6周后仍保持有益效果，并观察到一些有趣的相互作用。结论，通过不同的分子机制，所测定的减肥策略可有效纠正HFD的致肥胖作用以及肝功能的相关改变。在干预后维持期间避免体重恢复的有益效果也很明显。