Increased Adipose Tissue in Male and Female Estrogen receptor-α Knockout Mice

• Published in: Proceedings of the National Academy of Sciences - PNAS 2000-11, Vol.97 (23), p.12729-12734
• Main Authors: Heine, P. A., Taylor, J. A., Iwamoto, G. A., Lubahn, D. B., Cooke, P. S.
• Format: Article
• Language: English
• Subjects: Adipocytes; Adipocytes - cytology; Adipose Tissue - physiology; Adipose Tissue, Brown - physiology; Adipose tissues; Animals; Biochemistry; Biological Sciences; Body Weight; Cell Count; Energy Metabolism; Estrogen Receptor alpha; Estrogens; Female; Female animals; Glucose Tolerance Test; Insulin; Insulin - blood; Male; Male animals; Mice; Mice, Knockout; Obesity; Organ Size; Receptors, Estrogen - genetics; Receptors, Estrogen - physiology; Rodents; Tissues; Veterinary services; White adipose tissue
• ISSN: 0027-8424; 1091-6490
• DOI: 10.1073/pnas.97.23.12729

Estrogen regulates the amount of white adipose tissue (WAT) in females, but its role in males and whether WAT effects involve estrogen receptor-α (ERα ) or ERβ were unclear. We analyzed the role of ERα in WAT and brown adipose tissue by comparing these tissues in wild-type (WT) and ERα -knockout (α ERKO) male and female mice. Brown adipose tissue weight was similar in α ERKO and WT males at all ages. Progressive increases in WAT were seen in α ERKO males with advancing age. Epididymal, perirenal, and inguinal WAT weighed 139-185% more in α ERKO than in WT males by 270-360 days of age. Epididymal and perirenal adipocyte size was increased 20% in α ERKO males. Adipocyte number was 82-168% greater in fat pads of α ERKO vs. WT males. Compared with WT, 90-day-old α ERKO females had increases in fat pad weights (54-103%), adipocyte size, and number. Both α ERKO males and females had insulin resistance and impaired glucose tolerance, similar to humans lacking ERα or aromatase. Energy intake was equal in WT and α ERKO males, indicating that obesity was not induced by hyperphagia. In contrast, energy expenditure was reduced by 11% in α ERKO compared with WT males, indicating that altered energy expenditure may be important for the observed obesity. In summary, ERα absence causes adipocyte hyperplasia and hypertrophy, insulin resistance, and glucose intolerance in both sexes. These results are evidence that estrogen/ERα signaling is critical in female and male WAT; obesity in α ERKO males involves a mechanism of reduced energy expenditure rather than increased energy intake.