Singer Kanakadurga, Maley Nidhi, Mergian Taleen, DelProposto Jennifer, Cho Kae Won, Zamarron Brian F, Martinez-Santibanez Gabriel, Geletka Lynn, Muir Lindsey, Wachowiak Phillip, Demirjian Chaghig, Lumeng Carey N
From the Department of Pediatrics and Communicable Disease,
From the Department of Pediatrics and Communicable Disease.
J Biol Chem. 2015 May 22;290(21):13250-62. doi: 10.1074/jbc.M114.634568. Epub 2015 Apr 13.
Women of reproductive age are protected from metabolic disease relative to postmenopausal women and men. Most preclinical rodent studies are skewed toward the use of male mice to study obesity-induced metabolic dysfunction because of a similar protection observed in female mice. How sex differences in obesity-induced inflammatory responses contribute to these observations is unknown. We have compared and contrasted the effects of high fat diet-induced obesity on glucose metabolism and leukocyte activation in multiple depots in male and female C57Bl/6 mice. With both short term and long term high fat diet, male mice demonstrated increased weight gain and CD11c(+) adipose tissue macrophage content compared with female mice despite similar degrees of adipocyte hypertrophy. Competitive bone marrow transplant studies demonstrated that obesity induced a preferential contribution of male hematopoietic cells to circulating leukocytes and adipose tissue macrophages compared with female cells independent of the sex of the recipient. Sex differences in macrophage and hematopoietic cell in vitro activation in response to obesogenic cues were observed to explain these results. In summary, this report demonstrates that male and female leukocytes and hematopoietic stem cells have cell-autonomous differences in their response to obesity that contribute to an amplified response in males compared with females.
与绝经后女性和男性相比，育龄期女性免受代谢性疾病的影响。由于在雌性小鼠中观察到类似的保护作用，大多数临床前啮齿动物研究倾向于使用雄性小鼠来研究肥胖诱导的代谢功能障碍。肥胖诱导的炎症反应中的性别差异如何导致这些观察结果尚不清楚。我们比较并对比了高脂肪饮食诱导的肥胖对雄性和雌性C57Bl/6小鼠多个部位葡萄糖代谢和白细胞激活的影响。短期和长期高脂肪饮食下，尽管脂肪细胞肥大程度相似，但雄性小鼠与雌性小鼠相比体重增加更多，且CD11c(+)脂肪组织巨噬细胞含量更高。竞争性骨髓移植研究表明，与雌性细胞相比，肥胖诱导雄性造血细胞对循环白细胞和脂肪组织巨噬细胞的贡献更大，且与受体性别无关。观察到巨噬细胞和造血细胞在体外对致肥胖信号的激活存在性别差异，从而解释了这些结果。总之，本报告表明，雄性和雌性白细胞及造血干细胞在对肥胖的反应中存在细胞自主性差异，这导致雄性与雌性相比反应更强。
