Endocannabinoids and nitric oxide effect on high-fat food consumption in young rats

Abstract

Childhood obesity has become an increasingly prevalent disease worldwide, predisposing children and adolescents to physiological and psychological health complications, extending into adult years. Generally, weight gain is a result of a prolonged imbalance of food intake and energy expenditure. Further investigation of pathways affecting appetite regulation is required to develop safer, effective treatments for obesity. Two signals of interest are endocannabinoids (eCBs) and nitric oxide (NO), which have been shown to regulate food intake in adult animals. Research in young animals is limited, but it has been suggested that these neurotransmitters have different age-dependent effects on appetite in rats fed a standard diet. The current investigation was undertaken in fasted and non-fasted rats fed a high-fat diet, to gain insight into the effect of inhibiting or exciting eCB and NO pathways on palatable food consumption. In the first condition, young Sprague-Dawley rats were fasted for 24 hours, assigned randomly to a drug treatment or control group, and were refed for a 2-hour period, after which they were sacrificed and perfused. Food consumption data and accompanying body weight data were collected from each trial. In fasted animals, inhibiting the production of nitric oxide was shown to significantly reduce food intake and body weight, and blocking cannabinoid receptors also resulted in a significant decrease in food consumption compared to a control group receiving saline injections. In subsequent trials in non-fasted animals, blocking cannabinoid receptors resulted in a significant decrease in body weight compared to control animals. Results demonstrated that the manipulation of eCB and NO pathways in young rats fed a high-fat diet differed in their effects when compared to standard diet fed animals. These results confirm that further investigation is needed in non-fasted animals, as well as animals chronically exposed to a high-fat diet, to understand the physiological response of these pathways to drug interference.