Molecular Neurophysiology Laboratory, Department of Neurosciences Research, National Institute of Psychiatry Ramón de la Fuente Muñiz, Mexico City, Mexico.
J Neuroendocrinol. 2017 Nov;29(11). doi: 10.1111/jne.12541.
Negative energy balance promotes physiological adaptations that ensure the survival of animals. The hypothalamic-pituitary-thyroid axis regulates basal energy expenditure and its down-regulating adaptation to negative energy balance is well described: in fasting, the serum content of thyrotrophin (TSH) and thyroid hormones (TH) decreases, enhancing the survival odds of individuals. By contrast, dehydration-induced anorexic (DIA) rats present an impaired hypothalamic-pituitary-thyroid (HPT) axis adaptation despite their negative energy balance: increased circulating TSH levels. The implication of cocaine- and amphetamine-regulated transcript (CART), an anorexic peptide, in HPT axis function impairment and food-avoidance behaviour displayed by DIA animals is unknown. Because CART is co-expressed with the peptide that regulates the HPT axis in hypophysiotrophic paraventricular nucleus (PVN) neurones (TSH-releasing hormone), we analysed CART expression and possible implications with respect to high TSH levels of DIA animals. We examined whether changes in CART expression from the lateral hypothalamic area (LHA) and arcuate nucleus (ARC) could participate in food-avoidance of DIA rats. DIA and forced-food restricted (FFR) animals reduced their body weight and food intake. FFR rats had a down-regulation of their HPT axis (reduced serum TH and TSH content), whereas DIA animals had reduced TH but increased TSH levels. CART mRNA expression in the ARC decreased similarly between experimental groups and diminished in anterior, medial PVN and in LHA of FFR animals, whereas DIA animals showed unchanged levels. This impaired CART mRNA expression in the anterior PVN and LHA could be related to the aberrant feeding behaviour of DIA rats but not to their deregulated HPT axis function.
负能平衡促进了生理适应，确保了动物的生存。下丘脑-垂体-甲状腺轴调节基础能量消耗，其对负能平衡的下调适应已有很好的描述：在禁食时，促甲状腺素（TSH）和甲状腺激素（TH）的血清含量下降，增强了个体的生存几率。相比之下，脱水诱导的厌食（DIA）大鼠尽管处于负能平衡状态，但下丘脑-垂体-甲状腺（HPT）轴的适应能力受损：循环 TSH 水平增加。可卡因和安非他命调节转录物（CART），一种厌食肽，在 DIA 动物的 HPT 轴功能障碍和避免进食行为中的作用尚不清楚。因为 CART 与调节腺垂体促甲状腺激素释放激素的肽共同表达于下丘脑室旁核（PVN）神经元中，我们分析了 CART 表达及其对 DIA 动物高 TSH 水平的可能影响。我们检查了来自外侧下丘脑区域（LHA）和弓状核（ARC）的 CART 表达变化是否可能参与 DIA 大鼠的食物回避。DIA 和强制进食限制（FFR）动物的体重和食物摄入量减少。FFR 动物的 HPT 轴受到下调（血清 TH 和 TSH 含量降低），而 DIA 动物的 TH 降低但 TSH 水平升高。ARC 中的 CART mRNA 表达在实验组之间相似地减少，在 FFR 动物的前、中 PVN 和 LHA 中减少，而 DIA 动物的表达水平不变。这种前 PVN 和 LHA 中 CART mRNA 表达的受损可能与 DIA 大鼠异常的进食行为有关，但与它们失调的 HPT 轴功能无关。
