Dietary fat stimulates endogenous enkephalin and dynorphin in the paraventricular nucleus: role of circulating triglycerides.

The opioid peptides enkephalin (ENK) and dynorphin (DYN), when injected into the hypothalamus, are known to stimulate feeding behavior and preferentially increase the ingestion of a high-fat diet. Studies of another peptide, galanin (GAL), with similar effects on feeding demonstrate that a high-fat diet, in turn, can stimulate the expression of this peptide in the hypothalamus. The present study tested different diets and variable periods of high- vs. low-fat diet consumption to determine whether the opioid peptides respond in a similar manner as GAL. In six experiments, the effects of dietary fat on ENK and DYN were examined in three hypothalamic areas: the paraventricular nucleus (PVN), perifornical hypothalamus (PFH), and arcuate nucleus (ARC). The results demonstrated that the ingestion of a high-fat diet increases gene expression and peptide levels of both ENK and DYN in the hypothalamus. The strongest and most consistent effect is seen in the PVN. In this nucleus, ENK and DYN are increased by 50-100% after 1 wk, 1 day, 60 min, and even 15 min of high-fat diet consumption. While showing some effect in the PFH, these peptides in the ARC are considerably less responsive, exhibiting no change in response to the briefer periods of diet intake. This effect of dietary fat on PVN opioids can be observed with diets equal in caloric density and palatability and without a change in caloric intake, body weight, fat pad weight, or levels of insulin or leptin. The data reveal a strong and consistent association between these peptides and a rise in circulating levels of triglycerides, supporting a role for these lipids in the fat-induced stimulation of opioid peptides in the PVN, similar to GAL.