Effects of cannabinoid modulation on hypothalamic nesfatin-1 and insulin resistance.

Both nesfatin-1 and cannabinoid systems involved in the regulation of sleep, metabolism, and food intake. The relationship between cannabinoid system and nesfatin-1 levels remains to be elucidated. This study investigated nesfatin-1 and insulin resistance in 72-h rapid eye movement (REM) sleep-deprived mice under the effects of cannabinoid, and cannabinoid receptors CB1R and CB2R blocking. Sixty mice were exposed to 72-h sleep deprivation. Groups and drug administrations were as follows: Group 1 (control) received injection of vehicle. Group 2 received WIN 55,212,2. Group 3 received AM251 (CB1R antagonist) followed by WIN 55,212,2 injection. Group 4 received SR144528 (CB2R antagonist) followed by WIN 55,212,2 injection. Group 5 received only AM251. Group 6 received only SR144528. Blood samples were collected 1 h after drug administration and prepared for biochemical measurements. Glucose levels were measured by glucometer, whereas insulin and nesfatin-1 levels were measured by ELISA. Central nesfatin-1 was also assessed using immunohistochemistry. One-way analysis of variance together with post hoc Tukey's test was used for inter-group comparisons. Serum nesfatin-1 levels were comparable in all study groups. Brain nesfatin-1 immune-positive cell count was lower in WIN group compared to controls. The administration of CB1R or CB2R antagonist prevented reduction in nesfatin-1-positive cell count. Insulin resistance was higher in WINCB2 and CB2 groups than in control and WINCB1 groups. Cannabinoid treatment reduced nesfatin-1 immunoreactivity in the central nervous system and this effect was prevented by either CB1R or CB2R antagonist pretreatment. Insulin resistance might be related to CB2 receptor activation which was independent from central nesfatin-1 immunoreactivity.