Tannenbaum B M, Brindley D N, Tannenbaum G S, Dallman M F, McArthur M D, Meaney M J
Developmental Neuroendocrinology Laboratory, Douglas Hospital Research Center, Montreal, Canada.
Am J Physiol. 1997 Dec;273(6):E1168-77. doi: 10.1152/ajpendo.1997.273.6.E1168.
High-fat feeding induces insulin resistance and increases the risk for the development of diabetes and coronary artery disease. Glucocorticoids exacerbate this hyperinsulinemic state, rendering an individual at further risk for chronic disease. The present studies were undertaken to determine whether dietary fat-induced increases in corticosterone (B) reflect alterations in the regulatory components of the hypothalamic-pituitary-adrenal (HPA) axis. Adult male rats were maintained on a high-fat (20%) or control (4%) diet for varying periods of time. Marked elevations in light-phase spontaneous basal B levels were evident as early as 7 days after fat diet onset, and B concentrations remained significantly elevated up to 21 days after fat diet onset compared with controls. In contrast, there were no significant effects on any parameters of spontaneous growth hormone secretory profiles, thus providing support for the specificity of the effects on the HPA axis. In a second study, all groups of rats fed the high-fat diet for 1, 9, or 12 wk exhibited significantly elevated levels of plasma adrenocorticotropic hormone, B, fatty acid, and glucose before, during, and/or at 20, 60, and/or 120 min after the termination of a restraint stress. Furthermore 12-wk fat-fed animals showed a significant resistance to insulin compared with normally fed controls. There were no differences in negative feedback efficacy in high-fat-fed rats vs. controls. Taken together, these results suggest that dietary fat intake acts as a background form of chronic stress, elevating basal B levels and enhancing HPA responses to stress.
高脂喂养会诱发胰岛素抵抗，并增加患糖尿病和冠状动脉疾病的风险。糖皮质激素会加剧这种高胰岛素血症状态，使个体面临更高的慢性病风险。本研究旨在确定饮食脂肪诱导的皮质酮（B）增加是否反映了下丘脑 - 垂体 - 肾上腺（HPA）轴调节成分的改变。成年雄性大鼠分别以高脂（20%）或对照（4%）饮食喂养不同时间段。早在高脂饮食开始后7天，光期自发基础B水平就明显升高，与对照组相比，高脂饮食开始后21天内B浓度一直显著升高。相比之下，对自发生长激素分泌谱的任何参数均无显著影响，从而支持了对HPA轴影响的特异性。在第二项研究中，所有高脂饮食喂养1、9或12周的大鼠组在束缚应激终止前、期间和/或终止后20、60和/或120分钟时，血浆促肾上腺皮质激素、B、脂肪酸和葡萄糖水平均显著升高。此外，与正常喂养的对照组相比，高脂喂养12周的动物表现出明显的胰岛素抵抗。高脂喂养大鼠与对照组在负反馈效能方面没有差异。综上所述，这些结果表明饮食脂肪摄入作为一种慢性应激的背景形式，会升高基础B水平并增强HPA对应激的反应。
