Estrogen controls lipolysis by up-regulating alpha2A-adrenergic receptors directly in human adipose tissue through the estrogen receptor alpha. Implications for the female fat distribution

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Abdomen
  • Adipocytes / metabolism
  • Adipose Tissue / anatomy & histology
  • Adipose Tissue / drug effects
  • Adipose Tissue / metabolism*
  • Adrenergic alpha-Antagonists / metabolism
  • Estradiol / metabolism
  • Estradiol / pharmacology
  • Estrogen Receptor alpha
  • Estrogens / physiology*
  • Female
  • Humans
  • In Vitro Techniques
  • Lipolysis / drug effects
  • Lipolysis / physiology*
  • Lipoprotein Lipase / antagonists & inhibitors
  • RNA, Messenger / metabolism
  • Receptors, Adrenergic / genetics
  • Receptors, Adrenergic, alpha-2 / metabolism*
  • Receptors, Estrogen / physiology*
  • Sex Characteristics
  • Sterol Esterase / metabolism
  • Subcutaneous Tissue / metabolism
  • Up-Regulation
  • Yohimbine / metabolism


  • ADRA2A protein, human
  • Adrenergic alpha-Antagonists
  • Estrogen Receptor alpha
  • Estrogens
  • RNA, Messenger
  • Receptors, Adrenergic
  • Receptors, Adrenergic, alpha-2
  • Receptors, Estrogen
  • Yohimbine
  • Estradiol
  • Sterol Esterase
  • Lipoprotein Lipase