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Diabetes 52:268-276, 2003
© 2003 by the American Diabetes Association, Inc.

Sexual Differentiation, Pregnancy, Calorie Restriction, and Aging Affect the Adipocyte-Specific Secretory Protein Adiponectin

Terry P. Combs1, Anders H. Berg1, Michael W. Rajala1, Simon Klebanov2, Puneeth Iyengar1, José C. Jimenez-Chillaron3, Mary Elizabeth Patti3, Sabra L. Klein4, Robert S. Weinstein5, and Philipp E. Scherer1,6

1 Department of Cell Biology, Albert Einstein College of Medicine, Bronx, New York
2 Obesity Research Center, Saint Luke’s-Roosevelt Hospital Center, Columbia University College of Physicians and Surgeons, New York, New York
3 Research Division, Joslin Diabetes Center, Boston, Massachusetts
4 W. Harry Feinstone Department of Molecular Microbiology & Immunology, Johns Hopkins Bloomberg School of Public Health, Baltimore, Maryland
5 Bone Morphometry Laboratory, Division of Endocrinology and Metabolism, Center for Osteoporosis and Metabolic Bone Diseases, Department of Internal Medicine, and the Central Arkansas Veterans Healthcare System, University of Arkansas for Medical Sciences, Little Rock, Arkansas
6 Diabetes Research and Training Center, Albert Einstein College of Medicine, Bronx, New York

Adiponectin or adipocyte complement-related protein of 30 kDa (Acrp30) is a circulating protein produced exclusively in adipocytes. Circulating Acrp30 levels have been associated with insulin sensitivity in adult mice and humans, yet the Acrp30 profile over the lifespan and its hormonal regulation in vivo have not been previously described. Hence, we set forth to determine whether hormonal and metabolic changes associated with sexual maturation, reproduction, aging, and calorie restriction affect Acrp30. In mice, Acrp30 levels increase during sexual maturation by 4-fold in males and 10-fold in females. Neonatal castration (CX) allows Acrp30 of adults to reach female levels. CX in adults does not lead to female Acrp30 levels unless glucocorticoid exposure is elevated simultaneously by implant. Ovariectomy of infant mice does not interfere with the pubertal rise of Acrp30. However, ovariectomy in adults increases Acrp30. Estrogen suppressed Acrp30 in mice and 3T3-L1 adipocytes. In parallel to changes in estrogen action, Acrp30 decreased in late gestation but increased in both calorie-restricted and old (anovulatory) mice. The reduction of Acrp30 in lactating dams is consistent with a suppressive effect of prolactin and a stimulating effect of bromocriptine. In summary, Acrp30 levels in serum are under complex hormonal control and may play a key role in determining systemic insulin sensitivity under the respective conditions.


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