Caloric restriction, physical exercise, and CB1 receptor blockade as an efficient combined strategy for bodyweight control and cardiometabolic status improvement in male rats

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.Spanish Ministry of Science, Innovation and UniversitiesEuropean Commission DEP2014-58296-R RTC-2017-6540-1 RTI2018-100934-B-I00European Commissio

Aerobic interval exercise improves parameters of Non Alcoholic Fatty Liver Disease (NAFLD) and other alterations of metabolic syndrome in obese Zucker rats.

Metabolic syndrome (MS) is a group of metabolic alterations that increase the susceptibility to cardiovascular disease and type 2 diabetes. Nonalcoholic fatty liver disease has been described as the liver manifestation of MS. We aimed to test the beneficial effects of an aerobic interval training (AIT) protocol on different biochemical, microscopic, and functional liver alterations related to the MS in the experimental model of obese Zucker rat. Two groups of lean and obese animals (6 weeks old) followed a protocol of AIT (4 min at 65%-80% of maximal oxygen uptake, followed by 3 min at 50%-65% of maximal oxygen uptake for 45-60 min, 5 days/week, 8 weeks of experimental period), whereas 2 control groups remained sedentary. Obese rats had higher food intake and body weight (P < 0.0001) and suffered significant alterations in plasma lipid profile, area under the curve after oral glucose overload (P < 0.0001), liver histology and functionality, and antioxidant status. The AIT protocol reduced the severity of alterations related to glucose and lipid metabolism and increased the liver protein expression of PPARγ, as well as the gene expression of glutathione peroxidase 4 (P < 0.001). The training protocol also showed significant effects on the activity of hepatic antioxidant enzymes, although this action was greatly influenced by rat phenotype. The present data suggest that AIT protocol is a feasible strategy to improve some of the plasma and liver alterations featured by the MS

Changes on metabolic parameters induced by acute cannabinoid administration (CBD, THC) in a rat experimental model of nutritional vitamin A deficiency

Introduction: Vitamin A deficiency can result from malnutrition, malabsorption of vitamin A, impaired vitamin metabolism associated with liver disease, or chronic debilitating diseases like HIV infection or cancer. Background & aims: Cannabis administration has been described as a palliative symptom management therapy in such pathological stages. Therefore, this research aimed to study the effects of acute administration of cannabidiol (CBD) or thetrahydrocannabinol (THC) on the levels of retinol in plasma and in the liver, and biochemical parameters related to lipid and glucose metabolism (cholesterolaemia, triglyceridemia and glycemia) in a rat experimental model of vitamin A deficiency. Methods: The experimental animal model of Vitamin A deficiency was developed during a 50-day experimental period in which rats consumed a vitamin A-free diet. Cannabidiol (10 mg/kg body weight) or thetrahydrocannabinol (5 mg/kg body weight) were administered intraperitoneally 2 hours prior to sacrifice of the animals. Results: The nutritional deficiency caused a significant decrease in plasmatic and liver contents of retinol and biochemical parameters of glycemic, lipidic, and mineral metabolism. Acute intraperitoneal administration of Cannabidiol and thetrahydrocannabinol did not improve the indices of vitamin A status in either control or vitamin A-deficient rats. However, it had a significant effect on specific biochemical parameters such as glucose, triglycerides, and cholesterol. Conclusion: Under our experimental conditions, the reported effects of cannabinoid administration on certain signs of nutritional vitamin A deficiency appeared to be mediated through mechanisms other than changes in retinol metabolism or its mobilization after the acute administration of such compounds

Bioavailability and biotransformation of linolenic acid from basil seed oil as a novel source of omega-3 fatty acids tested on a rat experimental model.

Basil is an aromatic herb with a high concentration of bioactive compounds. The oil extracted from its seeds is a good source of α-linolenic acid (ALA) and also provides substantial amounts of linoleic acid (LA). This study aimed to test the bioavailability of the oil derived from basil seeds and its effects on different physiological parameters using 7-15% dietary inclusion levels. Furthermore, the assimilation of LA and ALA and their transformation in long-chain polyunsaturated fatty acids (LC-PUFAs) have been studied. Digestive utilization of total fat from basil seed oil (BSO) was high and similar to that of olive oil used as a control. Consumption of BSO resulted in increased LA and ALA levels of the plasma, liver, and erythrocyte membrane. In addition, the transformation of LA to arachidonic acid (ARA) was decreased by the high dietary intake of ALA which redirected the pathway of the Δ-6 desaturase enzyme towards the transformation of ALA into eicosapentaenoic acid (EPA). No alterations of hematological and plasma biochemical parameters were found for the 7 and 10% dietary inclusion levels of BSO, whereas a decrease in the platelet count and an increase in total- and HDL-cholesterol as well as plasma alkaline phosphatase (ALP) were found for a 15% BSO dose. In conclusion, BSO is a good source of ALA to be transformed into EPA and decrease the precursor of the pro-inflammatory molecule ARA. This effect on the levels of EPA in different tissues offers potential for its use as a dietary supplement, novel functional food, or a constituent of nutraceutical formulations to treat different pathologies

The Combined Intervention with Germinated Vigna radiata and Aerobic Interval Training Protocol Is an Effective Strategy for the Treatment of Non-Alcoholic Fatty Liver Disease (NAFLD) and Other Alterations Related to the Metabolic Syndrome in Zucker Rats

Metabolic syndrome (MetS) is a group of related metabolic alterations that increase the risk of developing non-alcoholic fatty liver disease (NAFLD). Several lifestyle interventions based on dietary treatment with functional ingredients and physical activity are being studied as alternative or reinforcement treatments to the pharmacological ones actually in use. In the present experiment, the combined treatment with mung bean (Vigna radiata), a widely used legume with promising nutritional and health benefits that was included in the experimental diet as raw or 4 day-germinated seed flour, and aerobic interval training protocol (65–85% VO2 max) has been tested in lean and obese Zucker rats following a 2 × 2 × 2 (2 phenotypes, 2 dietary interventions, 2 lifestyles) factorial ANOVA (Analysis of Variance) statistical analysis. Germination of V. radiata over a period of four days originated a significant protein hydrolysis leading to the appearance of low molecular weight peptides. The combination of 4 day-germinated V. radiata and aerobic interval training was more efficient compared to raw V. radiata at improving the aerobic capacity and physical performance, hepatic histology and functionality, and plasma lipid parameters as well as reverting the insulin resistance characteristic of the obese Zucker rat model. In conclusion, the joint intervention with legume sprouts and aerobic interval training protocol is an efficient treatment to improve the alterations of glucose and lipid metabolism as well as hepatic histology and functionality related to the development of NAFLD and the MetS