Sex and Depot Differences in Adipocyte Insulin Sensitivity and Glucose Metabolism
Yazmin Macotela ,
Jeremie Boucher ,
Thien T. Tran and
C. Ronald Kahn
From Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts.
Corresponding author: C. Ronald Kahn, c.ronald.kahn{at}joslin.harvard.edu .
Abstract
OBJECTIVE To investigate how insulin sensitivity and glucose metabolism differ in adipocytes between different fat depots of male and
female mice and how sex steroids contribute to these differences.
RESEARCH DESIGN AND METHODS Adipocytes from intra-abdominal/perigonadal (PG) and subcutaneous (SC) adipose tissue from normal, castrated, or steroid-implanted
animals were isolated and analyzed for differences in insulin sensitivity and glucose metabolism.
RESULTS Adipocytes from both PG and SC depots of females have increased lipogenic rates compared with those from males. In females,
intra-abdominal PG adipocytes are more insulin-sensitive than SC adipocytes and more insulin-sensitive than male adipocytes
from either depot. When stimulated by low physiological concentrations of insulin, female PG adipocytes show a robust increase
in Akt and extracellular signal–related kinase (ERK) phosphorylation and lipogenesis, whereas male adipocytes show activation
only at higher insulin concentrations. Adipocytes from females have higher mRNA/protein levels of several genes involved in
glucose and lipid metabolism. After castration, adipocytes of male mice showed increased insulin sensitivity and increased
lipogenic rates, whereas adipocytes of females demonstrate decreased lipid production. Increasing estrogen above physiological
levels, however, also reduced lipid synthesis in females, whereas increasing dihydrotestosterone in males had no effect.
CONCLUSIONS There are major sex differences in insulin sensitivity in adipose tissue, particularly in the intra-abdominal depot, that
are regulated by physiological levels of sex steroids. The increased sensitivity to insulin and lipogenesis observed in adipocytes
from females may account for their lower level of insulin resistance and diabetes risk despite similar or higher fat content
than in males.
Footnotes
The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore
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Received August 1, 2008.
Accepted December 28, 2008.
Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work
is not altered. See http://creativecommons.org/licenses/by-nc-nd/3.0/ for details.
© 2009 by the American Diabetes Association....

Sex and Depot Differences in Adipocyte Insulin Sensitivity and Glucose Metabolism

10.2337/db08-1054