title: Differences in Hematopoietic Stem Cells Contribute to Sexually Dimorphic Inflammatory Responses to High Fat Diet-induced Obesity.
abstract: 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.
authors: From the Department of Pediatrics and Communicable Disease, ksinger@umich.edu.
authors: Kanakadurga
authors: K
authors: Singer
authors: From the Department of Pediatrics and Communicable Disease.
authors: Nidhi
authors: N
authors: Maley
authors: From the Department of Pediatrics and Communicable Disease.
authors: Taleen
authors: T
authors: Mergian
authors: From the Department of Pediatrics and Communicable Disease.
authors: Jennifer
authors: J
authors: DelProposto
authors: the Soonchunhyang Institute of Medi-bio Science (SIMS), Soonchunhyang University, Cheonan-si, Chungcheongnam-do 330-930, Korea, and.
authors: Kae Won
authors: KW
authors: Cho
authors: From the Department of Pediatrics and Communicable Disease, the Graduate Program in Immunology, and.
authors: Brian F
authors: BF
authors: Zamarron
authors: the Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors: Gabriel
authors: G
authors: Martinez-Santibanez
authors: From the Department of Pediatrics and Communicable Disease.
authors: Lynn
authors: L
authors: Geletka
authors: From the Department of Pediatrics and Communicable Disease.
authors: Lindsey
authors: L
authors: Muir
authors: the College of Literature, Sciences, and Arts, University of Michigan, Ann Arbor, Michigan 48103.
authors: Phillip
authors: P
authors: Wachowiak
authors: the College of Literature, Sciences, and Arts, University of Michigan, Ann Arbor, Michigan 48103.
authors: Chaghig
authors: C
authors: Demirjian
authors: From the Department of Pediatrics and Communicable Disease, the Graduate Program in Immunology, and the Graduate Program in Cellular and Molecular Biology, University of Michigan Medical School, Ann Arbor, Michigan 48109.
authors: Carey N
authors: CN
authors: Lumeng
mesh_terms: D000273:Adipose Tissue / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D000818:Animals; D015415:Biomarkers / Q000032:analysis; D001786:Blood Glucose / Q000378:metabolism*; D002478:Cells, Cultured; D003114:Colony-Forming Units Assay; D059305:Diet, High-Fat / Q000009:adverse effects*; D005260:Female; D005434:Flow Cytometry; D005951:Glucose Tolerance Test; D006412:Hematopoietic Stem Cells / Q000166:cytology* / Q000378:metabolism; D007150:Immunohistochemistry; D007249:Inflammation / Q000150:complications / Q000276:immunology* / Q000473:pathology; D008055:Lipids / Q000032:analysis; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D038042:Myelopoiesis / Q000502:physiology; D009765:Obesity / Q000209:etiology* / Q000378:metabolism / Q000473:pathology; D012737:Sex Factors; D015430:Weight Gain
chemical_list: D015415:Biomarkers; D001786:Blood Glucose; D008055:Lipids
keywords: adipose tissue; adipose tissue inflammation; diet-induced obesity; hematopoiesis; inflammation; metabolism; metainflammation; obesity; sexually dimorphic