Department of Physiology, Institute of Nutrition and Food Technology (INyTA), Centre for Biomedical Research, Centre for Research in Sport and Health (IMUDS), Universidad de Granada, Avda. del Conocimiento S/N. Armilla (18100), Granada, Spain.
Department of Pharmacology, School of Pharmacy, Biohealth Research Institute, Centre for Biomedical Research, Universidad de Granada, Granada, Spain.
Sci Rep. 2021 Feb 19;11(1):4286. doi: 10.1038/s41598-021-83709-9.
Obesity is critically associated with the development of insulin resistance and related cardiovascular and kidney diseases. Several strategies for weight loss have been developed but most of them exhibit a post-intervention rebound effect. Here, we aimed to design combined weight-loss strategies of caloric restriction, physical exercise, and administration of a CB1 receptor blocker to inhibit food intake that also accomplish the objectives of lost-weight maintenance and improvement of cardiovascular and renal function. Diet-induced obesity (DIO) was generated in Sprague Dawley rats for 12 weeks to test the effects of single or combined strategies (i.e. caloric restriction, mixed training protocol, and/or administration of appetite suppressant) on caloric intake, body weight, cardiovascular and renal functionality resulting from a weight-loss intervention period of 3 weeks followed by 6 weeks of weight maintenance. Consumption of a high-fat diet (HFD) caused a significant increase in body weight (5th week of the experimental period) and led to the development of insulin resistance, cardiovascular, and renal alterations. The different interventions tested, resulted in a significant body weight loss and improved glucose metabolism, aerobic capacity, electrocardiographic parameters, vascular expression of adhesion molecules and inflammatory mediators, and renal functionality, reaching values similar to the control normocaloric group or even improving them. Successful maintenance of lost weight was achieved along a 6-week maintenance period in addition to adequate health status. In conclusion, the weight-loss and maintenance intervention strategies tested were efficient at reversing the obesity-related alterations in body weight, glucose metabolism, aerobic capacity, cardiovascular and renal functionality. The beneficial action was very consistent for caloric restriction and physical exercise, whereas administration of a CB1 receptor blocker complemented the effects of the prior interventions in some parameters like body weight or aerobic capacity, and showed specific actions in renal status, increasing glomerular filtration rate and diuresis. Overall, the novelty of our study relies on the easy implementation of combined strategies for effective weight management that resulted in significant health benefits.
肥胖与胰岛素抵抗以及相关的心脑血管和肾脏疾病的发生发展密切相关。目前已经开发了几种减肥策略，但大多数都表现出干预后的反弹效应。在这里，我们旨在设计一种联合减肥策略，包括热量限制、体育锻炼和给予 CB1 受体阻滞剂以抑制食欲，从而达到减肥和维持、改善心脑血管和肾功能的目标。通过对 Sprague Dawley 大鼠进行为期 12 周的饮食诱导肥胖（DIO），测试单一或联合策略（即热量限制、混合训练方案和/或给予食欲抑制剂）对热量摄入、体重、心血管和肾功能的影响，这些策略是在为期 3 周的减肥干预期后进行的，随后进行 6 周的体重维持期。高脂肪饮食（HFD）的摄入导致体重显著增加（实验期第 5 周），并导致胰岛素抵抗、心血管和肾脏改变的发生。测试的不同干预措施导致体重显著减轻，并改善葡萄糖代谢、有氧能力、心电图参数、血管黏附分子和炎症介质的表达以及肾功能，达到接近对照正常热量组的水平，甚至改善了这些指标。在 6 周的维持期内，成功地维持了减轻的体重，同时保持了良好的健康状态。总之，所测试的减肥和维持干预策略在逆转与肥胖相关的体重、葡萄糖代谢、有氧能力、心血管和肾功能改变方面是有效的。热量限制和体育锻炼的有益作用非常一致，而给予 CB1 受体阻滞剂在一些参数（如体重或有氧能力）上补充了先前干预措施的作用，并在肾脏状态方面显示出特定的作用，增加肾小球滤过率和利尿作用。总的来说，我们研究的新颖之处在于易于实施联合策略以有效进行体重管理，从而带来显著的健康益处。
