Effects of a High‐Fat Diet and Strain on Hypothalamic Gene Expression in Rats

Objective: This study was designed to investigate whether dietary fat and genetic background might differentially alter the expression of hypothalamic genes involved in food intake. Research Methods and Procedures: Three‐month‐old Osborne‐Mendel (OM) and S5B/Pl rats were fed either a high‐fat or a low‐fat diet for 14 days. mRNA for neuropeptide Y (NPY), corticotrophin‐releasing hormone, NPY Y‐1 receptor and Y‐5 receptor, and serotonin 2c (5‐HT2c) receptors were measured using Northern blotting or ribonuclease protection assays. Results: OM rats showed an increased expression of NPY and corticotrophin‐releasing hormone compared with S5B/Pl rats. The expression of NPY‐Y1 and ‐Y5 receptor mRNA was significantly higher in the hypothalamus of OM rats compared with S5B/Pl rats. The expression of 5HT‐2c receptor mRNA was significantly reduced in both strains of rats eating a high‐fat diet when compared with the animals eating the low‐fat diet. Discussion: These data suggest that over activity of the NPY system may contribute to the development of obesity in OM rats and that expression of the 5HT‐2c receptor gene may be modulated by dietary fat.