Diet‐dependent modulation of hippocampal expression of endocannabinoid signaling‐related proteins in cannabinoid antagonist‐treated obese rats

Abstract

Diet-induced obesity produces changes in endocannabinoid signaling (ECS), influencing the regulation of energy homeostasis. Recently, we demonstrated that, in high-fat-diet-fed rats, blockade of CB1 receptor by AM251 not only reduced body weight but also increased adult neurogenesis in the hippocampus, suggesting an influence of diet on hippocampal cannabinoid function. To further explore the role of hippocampal ECS in high-fat-diet-induced obesity, we investigated whether the immunohistochemical expression of the enzymes that produce (diacylglycerol lipase alpha and N-acyl phosphatidylethanolamine phospholipase D) and degrade (monoacylglycerol lipase and fatty acid amino hydrolase) endocannabinoids may be altered in the hippocampus of AM251 (3 mg/kg)-treated rats fed three different diets: standard diet (normal chow), high-carbohydrate diet (70% carbohydrate) and high-fat diet (60% fat). Results indicated that AM251 reduced caloric intake and body weight gain, and induced a modulation of the expression of ECS-related proteins in the hippocampus of animals exposed to hypercaloric diets. These effects were differentially restricted to either the 2-arachinodoyl glycerol or anandamide signaling pathways, in a diet-dependent manner. AM251-treated rats fed the high-carbohydrate diet showed a reduction of the diacylglycerol lipase alpha : monoacylglycerol lipase ratio, whereas AM251-treated rats fed the high-fat diet showed a decrease of the N-acyl phosphatidylethanolamine phospholipase D : fatty acid amino hydrolase ratio. These results are consistent with the reduced levels of hippocampal endocannabinoids found after food restriction. Regarding the CB1 expression, AM251 induced specific changes focused in the CA1 stratum pyramidale of high-fat-diet-fed rats. These findings indicated that the cannabinoid antagonist AM251 modulates ECS-related proteins in the rat hippocampus in a diet-specific manner. Overall, these results suggest that the hippocampal ECS participates in the physiological adaptations to different caloric diets.

A moderate diet restriction during pregnancy alters the levels of endocannabinoids and endocannabinoid-related lipids in the hypothalamus, hippocampus and olfactory bulb of rat offspring in a sex-specific manner

“…We also evaluated the endocannabinoid levels in the hippocampus, a brain structure involved in modulating emotional responses and where the endocannabinoid system plays an important role in memory formation and neurogenesis associated to metabolism-dependent mechanisms [29, 73]. Intriguingly, we found increased hippocampal levels of AA and 2-AG at birth in male offspring from calorie-restricted dams, which is opposite to the findings in the hypothalamus.…”

Maternal Caloric Restriction Implemented during the Preconceptional and Pregnancy Period Alters Hypothalamic and Hippocampal Endocannabinoid Levels at Birth and Induces Overweight and Increased Adiposity at Adulthood in Male Rat Offspring

“…It has been shown that circuits connecting hippocampus and hypothalamus are involved in the control of the hedonic aspects of eating (Petrovich, 2013) and that hippocampal endocannabinoid levels can be altered according to different types of diet (Rivera et al, 2012). For instance, decreased levels of hippocampal endocannabinioids have been reported after exposing young animals to prolonged starvation (Hanus et al, 2003).…”

Evaluation of plasma-free endocannabinoids and their congeners in abstinent cocaine addicts seeking outpatient treatment: impact of psychiatric co-morbidity

“…A six‐point external calibration curve prepared in the mobile phase (10:90, A : B) and spiked with 0.4–25 ng of NAEs and 0.8–50 ng of acyl‐glycerols was used for the quantification (Rivera et al . 2013a).…”