Ainslie D A, Morris M J, Wittert G, Turnbull H, Proietto J, Thorburn A W
Department of Medicine, University of Melbourne, Parkville, Victoria, Australia.
Int J Obes Relat Metab Disord. 2001 Nov;25(11):1680-8. doi: 10.1038/sj.ijo.0801806.
Altered fat distribution is a consequence of menopause, but the mechanisms responsible are unknown. Estrogen insufficiency in humans can be modeled using ovariectomized rats. We have shown that increased adiposity in these rats is due to reduced physical activity and transient hyperphagia, and can be reversed with 17beta-estradiol treatment. The aims of this study were to examine whether this altered energy balance is associated with circulating leptin insufficiency, central leptin insensitivity, decreased hypothalamic leptin receptor (Ob-Rb) expression, and/or increased hypothalamic neuropeptide Y (NPY).
Plasma leptin levels, adipose tissue ob gene expression, energy balance responses to i.c.v. leptin, hypothalamic Ob-Rb expression and NPY concentration in five separate hypothalamic regions were measured in adult female rats after either ovariectomy or sham operations.
Obesity was not associated with hypoleptinemia or decreased ob gene expression in ovariectomized rats; however, it was associated with insensitivity to central leptin administration. Food intake was less suppressed and spontaneous physical activity was less stimulated by leptin. This was not due to decreased hypothalamic Ob-Rb expression. NPY concentration in the paraventricular nucleus of the hypothalamus was elevated in the ovariectomized rats, consistent with leptin insensitivity; however this effect was transient and disappeared as body fat and leptin levels increased further and hyperphagia normalized.
Impaired central leptin sensitivity and overproduction of NPY may contribute to excess fat accumulation caused by estrogen deficiency.
脂肪分布改变是绝经的一个后果，但其相关机制尚不清楚。人类雌激素不足可通过切除卵巢的大鼠来模拟。我们已经表明，这些大鼠肥胖程度增加是由于身体活动减少和短暂性摄食过多所致，并且用17β-雌二醇治疗可使其逆转。本研究的目的是检查这种能量平衡改变是否与循环中瘦素不足、中枢性瘦素不敏感、下丘脑瘦素受体（Ob-Rb）表达降低和/或下丘脑神经肽Y（NPY）增加有关。
对成年雌性大鼠进行卵巢切除或假手术后，测量其血浆瘦素水平、脂肪组织ob基因表达、对脑室内注射瘦素的能量平衡反应、下丘脑Ob-Rb表达以及五个不同下丘脑区域的NPY浓度。
肥胖与卵巢切除大鼠的低瘦素血症或ob基因表达降低无关；然而，它与对中枢给予瘦素不敏感有关。瘦素对食物摄入的抑制作用较小，对自发身体活动的刺激作用也较小。这并非由于下丘脑Ob-Rb表达降低所致。卵巢切除大鼠下丘脑室旁核中的NPY浓度升高，这与瘦素不敏感一致；然而，这种作用是短暂的，随着体脂和瘦素水平进一步升高以及摄食过多恢复正常，该作用消失。
中枢性瘦素敏感性受损和NPY产生过多可能导致雌激素缺乏引起的脂肪过度堆积。
