Department of Psychiatry, McKnight Brain Institute, University of Florida, 1149 Newell Dr, Gainesville, FL 32611, USA.
Pharmacol Biochem Behav. 2013 Jan;103(3):573-81. doi: 10.1016/j.pbb.2012.10.012. Epub 2012 Oct 27.
Leptin is an adiposity hormone that plays an important role in regulating food intake and energy homeostasis. This study investigated the effects of a high-fat (HF) and a low-fat, high-carbohydrate/sugar (LF) diet on leptin sensitivity in the ventral tegmental area (VTA) in rats. The animals were exposed to a HF or LF diet for 16 weeks. Then the effects of intra-VTA leptin (150 and 500 ng/side, unilateral dose) on food intake and body weights were investigated while the animals were maintained on the HF or LF diet. Long-term exposure to the HF or LF diet led to similar body weight gain in these groups. The HF-fed animals consumed a smaller amount of food by weight than the LF-fed animals but both groups consumed the same amount of calories. The bilateral administration of leptin into the VTA decreased food intake (72 h) and body weights (48 h) to a similar degree in the HF and LF-fed animals. When the HF-fed animals were ranked by body weight gain it was shown that the diet-induced obese rats (HF-fed DIO, upper quartile for weight gain) were less sensitive to the effects of leptin on food intake and body weights than the diet-resistant rats (HF-fed DR, lower quartile for weight gain). A control experiment with fluorescent Cy3-labeled leptin showed that leptin did not spread beyond the borders of the VTA. This study indicates that leptin sensitivity in the VTA is the same in animals that are exposed to a HF or LF diet. However, HF-fed DIO rats are less sensitive to the effects of leptin in the VTA than HF-fed DR rats. Leptin resistance in the VTA might contribute to overeating and weight gain when exposed to a HF diet.
瘦素是一种脂肪激素，在调节食物摄入和能量平衡方面起着重要作用。本研究探讨了高脂肪（HF）和低脂肪、高碳水化合物/糖（LF）饮食对大鼠腹侧被盖区（VTA）瘦素敏感性的影响。动物暴露于 HF 或 LF 饮食 16 周。然后，在动物继续接受 HF 或 LF 饮食的情况下，研究了 VTA 内瘦素（150 和 500ng/侧，单侧剂量）对食物摄入和体重的影响。长期暴露于 HF 或 LF 饮食导致这些组的体重增加相似。HF 喂养的动物摄入的食物量比 LF 喂养的动物少，但两组摄入的热量相同。双侧 VTA 内给予瘦素可使 HF 和 LF 喂养的动物的食物摄入量（72 小时）和体重（48 小时）相似下降。当按体重增加对 HF 喂养的动物进行排序时，表明饮食诱导肥胖的大鼠（HF 喂养 DIO，体重增加的上四分位数）对瘦素对食物摄入和体重的影响的敏感性低于饮食抵抗的大鼠（HF 喂养 DR，体重增加的下四分位数）。用荧光 Cy3 标记的瘦素进行的对照实验表明，瘦素没有扩散到 VTA 的边界之外。本研究表明，暴露于 HF 或 LF 饮食的动物 VTA 中的瘦素敏感性相同。然而，HF 喂养 DIO 大鼠对 VTA 中瘦素的作用的敏感性低于 HF 喂养 DR 大鼠。VTA 中的瘦素抵抗可能导致暴露于 HF 饮食时过度进食和体重增加。
