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Existing experimental models insufficiently recapitulate \u201chuman-like\u201d obesity phenotypes, limiting the discovery of how severe obesity in pregnancy instructs vertical transmission of obesity. Here, via utility of thermoneutral housing and obesogenic diet feeding coupled to syngeneic mating of WT obese female and lean male mice on a C57BL\/6 background, we present a tractable, more \u201chuman-like\u201d approach to specifically investigate how maternal obesity contributes to offspring health. Using this model, we found that maternal obesity decreased neonatal survival, increased offspring adiposity, and accelerated offspring predisposition to obesity and metabolic disease. We also show that severe maternal obesity was sufficient to skew offspring microbiome and create a proinflammatory gestational environment that correlated with inflammatory changes in the offspring in utero and adulthood. Analysis of a human birth cohort study of mothers with and without obesity and their infants was consistent with mouse study findings of maternal inflammation and offspring weight gain propensity. Together, our results show that dietary induction of obesity in female mice coupled to thermoneutral housing can be used for future mechanistic interrogations of obesity and metabolic disease in pregnancy and vertical transmission of pathogenic traits.<\/jats:p>","DOI":"10.3390\/nu15234958","type":"journal-article","created":{"date-parts":[[2023,11,29]],"date-time":"2023-11-29T12:01:00Z","timestamp":1701259260000},"page":"4958","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Thermoneutral Housing Enables Studies of Vertical Transmission of Obesogenic Diet-Driven Metabolic Diseases"],"prefix":"10.3390","volume":"15","author":[{"given":"Jennifer L.","family":"Wayland","sequence":"first","affiliation":[{"name":"Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA"},{"name":"Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA"},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5225-801X","authenticated-orcid":false,"given":"Jessica R.","family":"Doll","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Matthew J.","family":"Lawson","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Traci E.","family":"Stankiewicz","sequence":"additional","affiliation":[{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4734-5597","authenticated-orcid":false,"given":"Jarren R.","family":"Oates","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA"},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Keisuke","family":"Sawada","sequence":"additional","affiliation":[{"name":"Immunology Graduate Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA"},{"name":"Medical Scientist Training Program, University of Cincinnati College of Medicine, Cincinnati, OH 45220, USA"},{"name":"Division of Immunobiology, Cincinnati Children\u2019s Hospital Medical Center, Cincinnati, OH 45229, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Michelle S. 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