Increased expression of mu opioid receptors in animals susceptible to diet-induced obesity

Stimulation of mu opioid receptors preferentially increases the intake of a high fat diet. In this paper we investigated whether there was a difference in the expression of mu opioid receptors between animals susceptible (Osborne–Mendel) or resistant (S5B/Pl) to obesity induced by eating a high fat diet. Immunohistochemical studies demonstrated that Osborne–Mendel rats eating a chow diet had an increased number of mu opioid receptors in the arcuate nucleus when compared to S5B/Pl rats. These immunohistochemical findings were supported by Real Time-PCR which demonstrated that the mRNA level of mu opioid receptors was also increased in the hypothalamus of Osborne–Mendel rats compared to S5B/Pl rats. Low doses of the mu opioid receptor agonist DAMGO [d-Ala2-N-Me-Phe4-Glycol5]-enkephalin administered to Osborne–Mendel rats caused a significant increase in the preference for a diet high in fat. The same doses of DAMGO switched the diet preference of S5B/Pl rats to high fat but did not significantly increase food intake. The combination of these findings suggests that the increased levels of hypothalamic mu opioid receptors in Osborne–Mendel rats may contribute to their preference for a diet high in fat and increase their susceptibility to becoming obese.