Journal article
Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice
The Journal of physiology, Vol.594(15), pp.4453-4466
08/01/2016
Handle:
https://hdl.handle.net/2376/109153
PMCID: PMC4967739
PMID: 27060371
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.
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Details
- Title
- Maternal obesity epigenetically alters visceral fat progenitor cell properties in male offspring mice
- Creators
- Xingwei Liang - Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USAQiyuan Yang - Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USAXing Fu - Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USACarl J Rogers - Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USABo Wang - Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USAHong Pan - Washington Centre for Muscle Biology and Department of Animal Sciences, Washington State University, Pullman, WA, USAMei-Jun Zhu - School of Food Sciences, Washington State University, Pullman, WA, USAPeter W Nathanielsz - Wyoming Pregnancy and Life Course Health Centre, Department of Animal Science, University of Wyoming, Laramie, Wyoming, USAMin Du - Beijing Advanced Innovation Centre for Food Nutrition and Human Health, College of Food Science & Nutritional Engineering, China Agricultural University, Beijing, China
- Publication Details
- The Journal of physiology, Vol.594(15), pp.4453-4466
- Academic Unit
- Animal Sciences, Department of
- Publisher
- England
- Grant note
- R01 HD067449 / NICHD NIH HHS R21 AG049976 / NIA NIH HHS
- Identifiers
- 99900547355801842
- Language
- English
- Resource Type
- Journal article