Curcumin Modulates Hippocampal Cannabinoid Receptor Expression in Mice Fed High-Fat and High-Fructose Diets

Abstract

Background: High-fat and high-fructose diets induce obesity and may cause physiological stress and alter the expression of cannabinoid receptor type 1 (CB1R) and cannabinoid receptor type 2 (CB2R). Curcumin may ameliorate these changes. Objectives: This study investigated the effects of curcumin on the modulation of the hippocampal endocannabinoid system in C57BL/6 mice under high-fat and high-fructose dietary conditions. Methods: A total of 42 5-week-old male C57BL/6 mice were fed for 14 weeks a (1) standard diet (SD), (2) SD plus fructose (SD+Fr), (3) SD plus curcumin and fructose (SD+C+Fr), (4) high-fat diet (HFD), (5) HFD plus curcumin (HFD+C), (6) HFD plus fructose (HFD+Fr), or (7) HFD plus curcumin and fructose (HFD+C+Fr). Results: At the end of treatment, mice in the HFD+Fr group had significantly greater body weight gain than those in the SD group (P < 0.05). Curcumin significantly attenuated weight gain in the HFD+C and HFD+C+Fr groups compared with their respective non-curcumin HFD groups (P < 0.05). Curcumin reduced CB1R and CB2R expression in HFD+C compared with that in HFD, whereas it increased CB1R and CB2R expression in HFD+C+Fr compared with that in HFD+Fr (P < 0.05). Hippocampal anandamide (AEA) was lower in HFD+Fr than in SD (P = 0.049) and in HFD+C than in HFD (P = 0.04). Hippocampal 2-arachidonoylglycerol (2-AG) was lower in HFD+Fr than in SD (P = 0.041) and in HFD+C than in both HFD (P = 0.032) and SD (P = 0.012). The decreases in AEA and 2-AG in HFD+C+Fr relative to SD were not statistically significant. Conclusions: High-fat and high-fructose diets increased body weight gain and altered hippocampal AEA and 2-AG levels, along with CB1R and CB2R expression. Curcumin attenuated hypercaloric diet-induced weight gain and modulated cannabinoid receptor expression in a diet-dependent manner, reducing receptor expression under high-fat conditions while increasing it under combined high-fat and fructose exposure. These findings indicate that diet-induced changes in endocannabinoid ligands are accompanied by selective alterations in receptor expression, particularly CB2R, and that curcumin modulates this system according to the metabolic context.