Pedersen Steen B, Kristensen Kurt, Hermann Pernille A, Katzenellenbogen John A, Richelsen Bjørn
Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus University Hospital, Denmark.
J Clin Endocrinol Metab. 2004 Apr;89(4):1869-78. doi: 10.1210/jc.2003-031327.
Estrogen seems to promote and maintain the typical female type of fat distribution that is characterized by accumulation of adipose tissue, especially in the sc fat depot, with only modest accumulation of adipose tissue intraabdominally. However, it is completely unknown how estrogen controls the fat accumulation. We studied the effects of estradiol in vivo and in vitro on human adipose tissue metabolism and found that estradiol directly increases the number of antilipolytic alpha2A-adrenergic receptors in sc adipocytes. The increased number of alpha2A-adrenergic receptors caused an attenuated lipolytic response of epinephrine in sc adipocytes; in contrast, no effect of estrogen on alpha2A-adrenergic receptor mRNA expression was observed in adipocytes from the intraabdominal fat depot. These findings show that estrogen lowers the lipolytic response in sc fat depot by increasing the number of antilipolytic alpha2A-adrenergic receptors, whereas estrogen seems not to affect lipolysis in adipocytes from the intraabdominal fat depot. Using estrogen receptor subtype-specific ligands, we found that this effect of estrogen was caused through the estrogen receptor subtype alpha. These findings demonstrate that estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic alpha2A-adrenergic receptors only in sc and not in visceral fat depots. Thus, our findings offer an explanation how estrogen maintains the typical female sc fat distribution because estrogen seems to inhibit lipolysis only in sc depots and thereby shifts the assimilation of fat from intraabdominal depots to sc depots.
雌激素似乎促进并维持典型的女性脂肪分布类型，其特征是脂肪组织堆积，尤其是皮下脂肪储存部位，而腹部内脂肪组织堆积较少。然而，雌激素如何控制脂肪堆积尚完全未知。我们研究了雌二醇在体内和体外对人体脂肪组织代谢的影响，发现雌二醇直接增加皮下脂肪细胞中抗脂解的α2A - 肾上腺素能受体数量。α2A - 肾上腺素能受体数量增加导致皮下脂肪细胞中肾上腺素的脂解反应减弱；相反，在内脏脂肪储存部位的脂肪细胞中未观察到雌激素对α2A - 肾上腺素能受体mRNA表达有影响。这些发现表明，雌激素通过增加抗脂解的α2A - 肾上腺素能受体数量降低皮下脂肪储存部位的脂解反应，而雌激素似乎不影响内脏脂肪储存部位脂肪细胞的脂解。使用雌激素受体亚型特异性配体，我们发现雌激素的这种作用是通过雌激素受体亚型α引起的。这些发现表明，雌激素仅在皮下而非内脏脂肪储存部位通过上调抗脂解的α2A - 肾上腺素能受体数量来减弱脂解反应。因此，我们的发现解释了雌激素如何维持典型的女性皮下脂肪分布，因为雌激素似乎仅抑制皮下储存部位的脂解，从而将脂肪同化从腹部储存部位转移到皮下储存部位。
