Excessive gestational weight gain (EGWG) closely associates with postpartum obesity. However, the causal role of EGWG in postpartum obesity has not been experimentally verified. The objective of this study was to determine whether and how EGWG causes long-term postpartum obesity.
C57BL/6 mice were fed with high-fat diet during gestation (HFFDG) or control chow, then their body composition and energy metabolism were monitored after delivery.
We found that HFFDG significantly increased gestational weight gain. After delivery, adiposity of HFFDG-treated mice (Preg-HF) quickly recovered to the levels of controls. However, 3 months after parturition, Preg-HF mice started to gain significantly more body fat even with regular chow. The increase of body fat of Preg-HF mice was progressive with aging and by 9 months after delivery had increased 2-fold above the levels of controls. The expansion of white adipose tissue (WAT) of Preg-HF mice was manifested by hyperplasia in visceral fat and hypertrophy in subcutaneous fat. Preg-HF mice developed low energy expenditure and UCP1 expression in interscapular brown adipose tissue (iBAT) in later life. Although blood estrogen concentrations were similar between Preg-HF and control mice, a significant decrease in estrogen receptor α (ERα) expression and hypermethylation of the ERα promoter was detected in the fat of Preg-HF mice 9 months after delivery. Interestingly, hypermethylation of ERα promoter and low ERα expression were only detected in adipocyte progenitor cells in both iBAT and WAT of Preg-HF mice at the end of gestation.
These results demonstrate that HFFDG causes long-term postpartum obesity independent of early postpartum fat retention. This study also suggests that HFFDG adversely programs long-term postpartum energy metabolism by epigenetically reducing estrogen signaling in both BAT and WAT.
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This work was supported by NIH grants HD069634 (J.S.), DK095132 (J.S.), HD007186 (W.W.H.Jr), HD068372(W.W.H.Jr), UL1TR001082(W.W.H.Jr), and American Diabetes grant 1–16-IBS-272 (J.S.). JS is the guarantor of this work and, as such, had full access to all of the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.
LQ, KC, JSW, SL, HG and GSF contributed research data. LQ, WWHJr. and JS contributed to research design and manuscript preparation.