Umeå Neurosteroid Research Center, Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, SE-901 85 Umeå, Sweden.
Umeå Neurosteroid Research Center, Department of Clinical Sciences, Obstetrics and Gynecology, Umeå University, SE-901 85 Umeå, Sweden.
Front Neuroendocrinol. 2018 Jan;48:70-77. doi: 10.1016/j.yfrne.2017.07.002. Epub 2017 Jul 8.
Obesity is strongly associated with ill health, primarily caused by consumption of excessive calories, and promoted (inter alia) by gamma-amino-butyric-acid (GABA) stimulating food intake by activating GABA receptors (primarily with α3 and α2 subunits) in the hypothalamic arcuate nucleus and paraventricular nucleus. Allopregnanolone is a potent positive GABA receptor modulating steroid (GAMS). As reviewed here, elevated allopregnanolone levels are associated with increases in food intake, preferences for energy-rich food, and obesity in humans and other mammals. In women with polycystic ovarian disease, high serum allopregnanolone concentrations are linked to uncontrolled eating, and perturbed sensitivity to allopregnanolone. Increases in weight during pregnancy also correlate with increases in allopregnanolone levels. Moreover, Prader-Willis syndrome is associated with massive overeating, absence of a GABA receptor (with compensatory >12-, >5- and >1.5-fold increases in α4, γ2, and α1, α3 subunits), and increases in the α4, βx, δ receptor subtype, which is highly sensitive to allopregnanolone. GABA and positive GABA-A receptor modulating steroids like allopregnanolone stimulates food intake and weight gain.
肥胖与健康不良密切相关，主要是由于摄入过多卡路里引起的，并且（除其他外）通过激活下丘脑弓状核和室旁核中的 GABA 受体（主要与 α3 和 α2 亚基结合）来促进食物摄入，从而促进肥胖。别孕烯醇酮是一种有效的正 GABA 受体调节性甾体（GAMS）。正如这里所综述的，升高的别孕烯醇酮水平与人类和其他哺乳动物的食物摄入量增加、对富含能量的食物的偏好以及肥胖有关。在多囊卵巢疾病的女性中，高血清别孕烯醇酮浓度与不受控制的饮食和对别孕烯醇酮的敏感性改变有关。怀孕期间体重增加也与别孕烯醇酮水平的增加相关。此外，普拉德-威利综合征与大量暴饮暴食、缺乏 GABA 受体（代偿性增加 12 倍、5 倍和 1.5 倍以上的 α4、γ2 和 α1、α3 亚基）以及对别孕烯醇酮高度敏感的 α4、βx、δ 受体亚型增加有关。GABA 和正 GABA-A 受体调节性甾体如别孕烯醇酮可刺激食物摄入和体重增加。
