title: Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice.
abstract: Maternal obesity reduces adipogenic progenitor density in offspring adipose tissue. The ability of adipose tissue expansion in the offspring of obese mothers is limited and is associated with metabolic dysfunction of adipose tissue when challenged with a high-fat diet. Maternal obesity induces DNA demethylation in the promoter of zinc finger protein 423, which renders progenitor cells with a high adipogenic capacity. Maternal obesity demonstrates long-term effects on the adipogenic capacity of progenitor cells in offspring adipose tissue, demonstrating a developmental programming effect.
  
  
  
  Maternal obesity (MO) programs offspring obesity and metabolic disorders, although the underlying mechanisms remain poorly defined. Progenitor cells are the source of new adipocytes. The present study aimed to test whether MO epigenetically predisposes adipocyte progenitors in the fat of offspring to adipogenic differentiation and subsequent depletion, which leads to a failure of adipose tissue plasticity under positive energy balance, contributing to adipose tissue metabolic dysfunction. C57BL/6 female mice were fed either a control diet (10% energy from fat) or a high-fat diet (45% energy from fat) for 8 weeks before mating. Male offspring of control (Con) and obese (OB) dams were weaned onto a regular (Reg) or obesogenic (Obe) diet until 3 months of age. At weaning, male OB offspring had a higher expression of Zinc finger protein 423 (zfp423), a key transcription factor in adipogenesis, as well as lower DNA methylation of its promoter in progenitors of epididymal fat compared to Con offspring, which was correlated with enhanced adipogenic differentiation. At 3 months of age, progenitor density was 30.9 ± 9.7% lower in OB/Obe compared to Con/Obe mice, accompanied by a limited expansion of the adipocyte number when challenged with a high-energy diet. This difference was associated with lower DNA methylation in the zfp423 promoter in the epididymal fat of OB/Obe offspring, which was correlated with greater macrophage chemotactic protein-1 and hypoxia-inducible factor 1α expression. In summary, MO epigenetically limits the expansion capacity of offspring adipose tissue, providing an explanation for the adipose metabolic dysfunction of male offspring in the setting of MO.
authors.affiliation: Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USA.
authors.forename: Xingwei
authors.initials: X
authors.lastname: Liang
authors.affiliation: Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USA.
authors.forename: Qiyuan
authors.initials: Q
authors.lastname: Yang
authors.affiliation: Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USA.
authors.forename: Xing
authors.initials: X
authors.lastname: Fu
authors.affiliation: Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USA.
authors.forename: Carl J
authors.initials: CJ
authors.lastname: Rogers
authors.affiliation: Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USA.
authors.forename: Bo
authors.initials: B
authors.lastname: Wang
authors.affiliation: Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USA.
authors.forename: Hong
authors.initials: H
authors.lastname: Pan
authors.affiliation: School of Food Sciences, Washington State University, Pullman, WA, USA.
authors.forename: Mei-Jun
authors.initials: MJ
authors.lastname: Zhu
authors.affiliation: Wyoming Pregnancy and Life Course Health Centre, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USA.
authors.forename: Peter W
authors.initials: PW
authors.lastname: Nathanielsz
authors.affiliation: Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USA.|Beijing Advanced Innovation Centre for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China.
authors.forename: Min
authors.initials: M
authors.lastname: Du
mesh_terms: D000818:Animals; D016207:Cytokines / Q000235:genetics; D019175:DNA Methylation; D004268:DNA-Binding Proteins / Q000235:genetics / Q000378:metabolism; D044127:Epigenesis, Genetic; D005260:Female; D050152:Intra-Abdominal Fat / Q000166:cytology* / Q000378:metabolism; D008297:Male; D039382:Maternal Nutritional Physiological Phenomena; D008810:Mice, Inbred C57BL; D009765:Obesity; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013234:Stem Cells / Q000502:physiology*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism
chemical_list: D016207:Cytokines; D004268:DNA-Binding Proteins; C484557:Ebfaz protein, mouse; D012333:RNA, Messenger; D014157:Transcription Factors