Differences in Hematopoietic Stem Cells Contribute to Sexually Dimorphic Inflammatory Responses to High Fat Diet Induced Obesity [Immunology]

April 13th, 2015 by Singer, K., Maley, N., Mergian, T., DelProposto, J., Cho, K. W., Zamarron, B. F., Martinez-Santibanez, G., Geletka, L., Muir, L., Wachowiak, P., Demirjian, C., Lumeng, C. N.

Women of reproductive age are protected from metabolic disease relative to post-menopausal women and men. Most preclinical rodent studies are skewed towards 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 (HFD) 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 HFD, male mice demonstrated increased weight gain and CD11c+ adipose tissue macrophage content compared to 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 to 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 HSCs have cell autonomous differences in their response to obesity that contributes to an amplified response in males compared to females.
  • Posted in Journal of Biological Chemistry, Publications
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