Peripheral leptin administration to ob/ob mice decreases the gene expression of hypothalamic mu opioid receptors

Abstract

Activation of mu opioid receptors make animals hyperphagic and increase their preference for a high fat diet. We have demonstrated that the gene and protein expression of this receptor population is significantly greater in the hypothalamus of obese animals. This warrants the consideration that the increased mu opioid receptors are potentiating the hyperphagia and the preference for a high fat diet that is associated with obesity. Utilizing ob/ob mice, we investigated the hypothesis that hypothalamic mu opioid receptors are increased in obesity due to an attenuation of leptin's anorexic effect. The gene expression of hypohtalamic mu opioid receptors was significantly greater in ob/ob mice compared to the control C57/B6 mice. Ob/ob mice given ad libitum access to a high fat diet for fourteen days gained more weight, were hyperphagic, had an increase in body fat, and a significantly greater gene expression of hypothalamic mu opioid receptors when compared to their low fat controls. When leptin was administered intraperitoneal (IP) to the ob/ob animals it resulted in a significant decrease in the gene expression of hypothalamic mu opioid receptors, body weight, food intake, and body fat percentage. Taken together, these data suggest that the development of leptin resistance in obese animals positively contributes to the increased gene expression of hypothalamic mu opioid receptors. DK R34‐32089