EFFECT OF DIET ON ENERGY METABOLISM

肥胖（ob/ob）小鼠和肥胖大鼠下丘脑 刀削减成为肥胖，即使配对到他们各自的 对照 因此，这些动物消耗的能量必须比 正常 我们的总体目标是确定神经内分泌和 负责提高膳食效率的细胞因子 这些肥胖动物的能量保持能力。 实验 为了确定为什么肾上腺切除术能进一步阻断 肥胖症的发展在ob/ob小鼠喂食高淀粉饮食，但 而在喂食高葡萄糖或高脂肪饮食的ob/ob小鼠中则没有。 的影响 这些饮食治疗对胰岛素分泌的神经控制， 离体胰岛对甲状腺单向摄取的影响 激素和皮质酮的肝脏和大脑，对交感神经 心脏和棕色脂肪组织中的神经系统活动， 通过棕色脂肪组织上的去甲肾上腺素转换评估 产热能力，以及参与 热调节产热在假手术能量平衡中的作用 手术和肾上腺切除的ob/ob和瘦小鼠将 确定。 假设中枢神经系统 糖皮质激素的作用部位， 肥胖的ob/ob小鼠，高胰岛素血症是关键的 将在ob/ob小鼠中糖皮质激素诱导的肥胖的介导物 评估。 ob/ob小鼠和大鼠的选择性比较 下丘脑的刀切将有助于确定关键因素 这使得这些动物能够保持较高的饮食能量。 这些数据应该会增加我们对饮食的理解- 肥胖症发展中的依赖性代谢因素，以及 应有助于确定更好的营养方法科普 预防和控制肥胖。

Obese (ob/ob) mice and rats with obesity-producing hypothalamic knife-cuts become obese even if pairfed to their respective controls. These animals must therefore expend less energy than normal. Our overall goal is to identify neuroendocrine and cellular factors responsible for the enhanced efficiency of dietary energy retention in these obese animals. Experiments are proposed to determine why adrenalectomy blocks further development of obesity in ob/ob mice fed a high-starch diet, but not in ob/ob mice fed high-glucose or high-fat diets. Effects of these dietary treatments on neural control of insulin secretion by isolated pancreatic islets, on unidirectional uptake of thyroid hormones and corticosterone by liver and brain, on sympathetic nervous system activity in heart and brown adipose tissue as assessed by norepinephrine turnover, on brown adipose tissue thermogenic capacity, and on the involvement of thermoregulatory thermogenesis in energy balance in sham- operated and adrenalectomized ob/ob and lean mice will be ascertained. The hypotheses that the central nervous system is the site of glucorticoid action responsible for development of obesity in ob/ob mice, and that hyperinsulinemia is the critical mediator of glucorticoid-induced obesity in ob/ob mice will be evaluated. Selective comparisons between ob/ob mice and rats with hypothalamic knife-cuts will help identify the key factors that permit high retention of dietary energy in these animals. These data should increase our understanding of the diet- dependent metabolic factors in development of obesity, and should aid in defining improved nutritional approaches to cope with the prevention and control of obesity.