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.