Heine P A, Taylor J A, Iwamoto G A, Lubahn D B, Cooke P S
Departments of Veterinary Biosciences and Kinesiology, University of Illinois, Urbana, IL 61802, USA.
Proc Natl Acad Sci U S A. 2000 Nov 7;97(23):12729-34. 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-alpha (ERalpha) or ERbeta were unclear. We analyzed the role of ERalpha in WAT and brown adipose tissue by comparing these tissues in wild-type (WT) and ERalpha-knockout (alphaERKO) male and female mice. Brown adipose tissue weight was similar in alphaERKO and WT males at all ages. Progressive increases in WAT were seen in alphaERKO males with advancing age. Epididymal, perirenal, and inguinal WAT weighed 139-185% more in alphaERKO than in WT males by 270-360 days of age. Epididymal and perirenal adipocyte size was increased 20% in alphaERKO males. Adipocyte number was 82-168% greater in fat pads of alphaERKO vs. WT males. Compared with WT, 90-day-old alphaERKO females had increases in fat pad weights (54-103%), adipocyte size, and number. Both alphaERKO males and females had insulin resistance and impaired glucose tolerance, similar to humans lacking ERalpha or aromatase. Energy intake was equal in WT and alphaERKO males, indicating that obesity was not induced by hyperphagia. In contrast, energy expenditure was reduced by 11% in alphaERKO compared with WT males, indicating that altered energy expenditure may be important for the observed obesity. In summary, ERalpha absence causes adipocyte hyperplasia and hypertrophy, insulin resistance, and glucose intolerance in both sexes. These results are evidence that estrogen/ERalpha signaling is critical in female and male WAT; obesity in alphaERKO males involves a mechanism of reduced energy expenditure rather than increased energy intake.
雌激素调节雌性动物体内白色脂肪组织（WAT）的数量，但其在雄性动物中的作用以及WAT效应是否涉及雌激素受体α（ERα）或雌激素受体β尚不清楚。我们通过比较野生型（WT）和ERα基因敲除（αERKO）雄性和雌性小鼠的这些组织，分析了ERα在WAT和棕色脂肪组织中的作用。在所有年龄段，αERKO雄性小鼠的棕色脂肪组织重量与WT雄性小鼠相似。随着年龄增长，αERKO雄性小鼠的WAT逐渐增加。到270 - 360日龄时，αERKO雄性小鼠的附睾、肾周和腹股沟WAT重量比WT雄性小鼠重139 - 185%。αERKO雄性小鼠的附睾和肾周脂肪细胞大小增加了20%。αERKO雄性小鼠脂肪垫中的脂肪细胞数量比WT雄性小鼠多82 - 168%。与WT相比，90日龄的αERKO雌性小鼠的脂肪垫重量（增加54 - 103%）、脂肪细胞大小和数量均增加。αERKO雄性和雌性小鼠均有胰岛素抵抗和葡萄糖耐量受损，类似于缺乏ERα或芳香化酶的人类。WT和αERKO雄性小鼠的能量摄入相等，这表明肥胖不是由摄食过多引起的。相反，与WT雄性小鼠相比，αERKO雄性小鼠的能量消耗减少了11%，这表明能量消耗的改变可能是观察到的肥胖的重要原因。总之，缺乏ERα会导致两性脂肪细胞增生和肥大、胰岛素抵抗和葡萄糖不耐受。这些结果证明雌激素/ERα信号在雌性和雄性WAT中至关重要；αERKO雄性小鼠的肥胖涉及能量消耗减少而非能量摄入增加的机制。
