Fisler J S, Shimizu H, Bray G A
Department of Medicine, School of Medicine, University of Southern California, Los Angeles 90033.
Physiol Behav. 1989 Mar;45(3):571-7. doi: 10.1016/0031-9384(89)90075-9.
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.
在两种对肥胖易感性不同的大鼠品系中，测量了全脑3-羟基丁酸、谷氨酸和γ-氨基丁酸（GABA）的浓度。S 5B/Pl大鼠在食用高脂饮食时对肥胖具有抗性，而奥斯本-孟德尔大鼠在食用相同饮食时则容易肥胖。我们检验了以下假设：S 5B/Pl大鼠和奥斯本-孟德尔大鼠的脑3-羟基丁酸、谷氨酸和GABA存在差异，并且这些底物/神经调节剂在主要是S 5B/Pl（抗性）大鼠食用高脂饮食时会发生改变。S 5B/Pl大鼠的血液和脑3-羟基丁酸浓度高于奥斯本-孟德尔大鼠（p小于0.05），但饮食影响不显著。脑谷氨酸浓度与3-羟基丁酸一样，S 5B/Pl大鼠高于奥斯本-孟德尔大鼠（p小于0.01），且不受饮食中添加脂肪的影响。脑GABA在品系间仅略有差异，但在两个品系中饮食添加脂肪后均增加（p小于0.05），S 5B/Pl大鼠增加幅度更大。与奥斯本-孟德尔大鼠相比，S 5B/Pl大鼠的大脑长期暴露于更高水平的3-羟基丁酸和谷氨酸中。因此，3-羟基丁酸是体重调节中的一个潜在信号。脑GABA随着脂肪喂养而增加，尤其是在S 5B/Pl大鼠中，这表明适应能量密集型饮食的能力可能是通过升高脑GABA来抑制食物摄入实现的。
