While a high-fat diet when compared to low-fat diet is known to produce 
overeating and health complications, less is known about the effects produced by 
fat-rich diets differing in their specific composition of fat. This study 
examined the effects of a high-fat diet containing relatively high levels of 
saturated compared to unsaturated fatty acids (HiSat) to a high-fat diet with 
higher levels of unsaturated fatty acids (USat). A HiSat compared to USat meal 
caused rats to consume more calories in a subsequent chow test meal. The HiSat 
meal also increased circulating levels of triglycerides (TG) and expression of 
the orexigenic peptides, galanin (GAL) in the hypothalamic paraventricular 
nucleus (PVN) and orexin (OX) in the perifornical lateral hypothalamus (PFLH). A 
similar increase in TG levels and PVN GAL and PFLH OX was also seen in rats 
given chronic access to the HiSat compared to USat diet, while neuropeptide Y 
(NPY) and agouti-related protein (AgRP) in the arcuate nucleus showed decreased 
expression. The importance of TG in producing these changes was supported by the 
finding that the TG-lowering medication gemfibrozil as compared to vehicle, when 
peripherally administered before consumption of a HiSat meal, significantly 
decreased the expression of OX, while increasing the expression of NPY and AgRP. 
These findings substantiate the importance of the fat composition in a diet, 
indicating that those rich in saturated compared to unsaturated fatty acids may 
promote overeating by increasing circulating lipids and specific hypothalamic 
peptides, GAL and OX, known to preferentially stimulate the consumption of a 
fat-rich diet.