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Estrogen Controls Lipolysis by Up-Regulating 2A-Adrenergic Receptors Directly in Human Adipose Tissue through the Estrogen Receptor . Implications for the Female Fat Distribution

Department of Endocrinology and Metabolism (S.B.P., K.K., P.A.H., B.R.), Aarhus Amtssygehus, Aarhus University Hospital; Faculty of Health Sciences (B.R.), Aarhus University, DK-8000 Aarhus C., Denmark; and Department of Chemistry (J.A.K.), University of Illinois, Urbana, Illinois 61801

Address all correspondence and requests for reprints to: Steen B. Pedersen, M.D., Ph.D., Department of Endocrinology and Metabolism, Aarhus Amtssygehus, Aarhus University Hospital, DK-8000 Aarhus C., Denmark. E-mail: sbp{at}dadlnet.dk.

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 2A-adrenergic receptors in sc adipocytes. The increased number of 2A-adrenergic receptors caused an attenuated lipolytic response of epinephrine in sc adipocytes; in contrast, no effect of estrogen on 2A-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 2A-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 .

These findings demonstrate that estrogen attenuates the lipolytic response through up-regulation of the number of antilipolytic 2A-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.

This work was supported by the Danish Medical Research Council; The Institute of Experimental Clinical Research, Aarhus University, Aarhus University Research Foundation; the Novo Nordic Foundation; and Grant PHS 5R37 DK15556 from the National Institutes of Health (to J.A.K.).

Abbreviations: BMI, Body mass index; Ct, threshold cycle; dbcAMP, dibutryl cAMP; ER, estrogen receptor; HRT, hormone replacement therapy; HSL, hormone-sensitive lipase; LPL, lipoprotein lipase; PPT, 4,4',4''-(4-propyl-[¹H]-pyrazole-1,3,5-triyl)trisphenol; THC, R,R-5,11-diethyl-5,6,11,12-tetrahydrochrysene-2,8,-diol.

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