Opioids

Humans can develop or be trained to like or dislike various foods by repeated exposure. The effect of this repeated exposure can lead to enhanced liking or even craving for a particular food. This is particularly true for sweet foods and fatty foods, the typical snack or junk foods, and appears to be centered in the nucleus [Page 561]accumbens and ventreal pallidum where opioids appear to increase the liking or craving mechanism. It is also likely that interconnection with other brain regions enhances this effect. The hypothalamus regulates short-term and long-term dietary intake by the synthesis of neuropeptides that have an orexigenic, increased eating effect, or anorectic, decreased eating effect.

When food is consumed, peripheral neuropeptides such as cholecystokinin, ghrelin, peptide YY, amylin, and bombesin provide feedback to the central nervous system to control gastrointestinal motility, enzyme secretion, and nutrient absorption in the short term, while leptin and insulin regulate nutrient absorption and storage in the long term. This complicated mechanism may help in the selection of foods, for example, sweet or fatty foods to satisfy one's opioid receptors.

Animal research has found that in obese mice and rats that a diaryl ether derivative of nicotinamide, a mu-opioid receptor antagonist has an anorectic effect. This was particularly pronounced in animals with deficient mu-opioid receptors. Antagonism of kappa-opioid receptors in rats led to decreased food intake, decreased energy expended, decreased core temperature, and a slight reduction in body weight, but the weight loss was directly related to decreased intake not as increased activity or metabolic rate. Rat studies have demonstrated that a high-fat diet can induce obesity and is associated with increased hypothalamic mu-opioid receptors. When these rats were infused with a mu-opioid agonist, they had higher systolic blood pressure and heart rates, a common finding in obesity. When they were infused with a mu-opioid antagonist, there was no increase in blood pressure or heart rate. The same has been shown for kappa-opioid receptors.

Human research suggests that endogenous opioids have a role in glucoregulation and the pathogenesis of obesity. These may be linked to the metabolic changes seen in obesity, insulin resistance, and polycystic ovary syndrome. Altered opioid levels seen in hyperinsulinemia and the increased opioid activity in postmenopausal women combined with increased central body fat distribution further suggest a role for opioids and selected foods in the obesity epidemic.