Whole brain concentrations of
3-hydroxybutyrate,
glutamate and
gamma-aminobutyric acid (
GABA) have been measured in two strains of rats with differing susceptibility to
obesity. S 5B/Pl rats are resistant to developing
obesity when eating a high-fat diet, whereas Osborne-Mendel rats readily develop
obesity when eating the same diet. We tested the hypotheses that brain
3-hydroxybutyrate,
glutamate and
GABA differ between S 5B/Pl rats and Osborne-Mendel rats, and that these substrates/
neuroregulators are altered when eating a high-fat diet primarily in S 5B/Pl (resistant) rats. Blood and brain
3-hydroxybutyrate concentrations were higher in S 5B/Pl rats than in Osborne-Mendel rats (p less than 0.05) but diet effects were not significant. Brain
glutamate concentration, like
3-hydroxybutyrate, was higher in S 5B/Pl rats than in Osborne-Mendel rats (p less than 0.01) and was not affected by adding fat to the diet. Brain
GABA differed only slightly between strains but increased after adding fat to the diet (p less than 0.05) in both strains with a greater increase occurring in S 5B/Pl rats. The brains of S 5B/Pl rats are chronically exposed to higher levels of
3-hydroxybutyrate and
glutamate than are those of Osborne-Mendel rats. Thus,
3-hydroxybutyrate is a potential signal in the regulation of
body weight. Brain
GABA increases with fat feeding, especially in S 5B/Pl rats, suggesting that the ability to adjust to an energy dense diet may be through suppression of food intake by elevated brain
GABA.