We hypothesised that maternal diet-induced-obesity has adverse consequences for offspring energy expenditure and susceptibility to obesity in adulthood, and that the prebiotic polydextrose (PDX) would prevent the consequences of programming by maternal obesity.
Female mice were fed a control (Con) or obesogenic diet (Ob) for 6 weeks prior to mating and throughout pregnancy and lactation. Half the obese dams were supplemented with 5% PDX (ObPDX) in drinking water throughout pregnancy and lactation. Offspring were weaned onto standard chow. At 3 and 6 months, offspring energy intake (EI) and energy expenditure (EE by indirect calorimetry) were measured, and a glucose-tolerance test performed. Offspring of control (OffCon), obese (OffOb) and PDX supplemented (OffObP) dams were subsequently challenged for 3 weeks with Ob, and energy balanced reassessed. Potential modifiers of offspring energy balance including gut microbiota and biomarkers of mitochondrial activity were also evaluated.
Six-month-old male OffOb demonstrated increased bodyweight (BW, P < 0.001) and white adipose tissue mass (P < 0.05), decreased brown adipose tissue mass (BAT, P < 0.01), lower night-time EE (P < 0.001) versus OffCon, which were prevented in OffObP. Both male and female OffOb showed abnormal glucose-tolerance test (peak [Glucose] P < 0.001; AUC, P < 0.05) which was prevented by PDX. The Ob challenge resulted in greater BW gain in both male and female OffOb versus OffCon (P < 0.05), also associated with increased EI (P < 0.05) and reduced EE in females (P < 0.01). OffObP were protected from accelerated BW gain on the OB diet compared with controls, associated with increased night-time EE in both male (P < 0.05) and female OffObP (P < 0.001). PDX also prevented an increase in skeletal muscle mtDNA copy number in OffOb versus OffCon (P < 0.01) and increased the percentage of Bacteroides cells in faecal samples from male OffObP relative to controls.
Maternal obesity adversely influences adult offspring energy balance and propensity for obesity, which is ameliorated by maternal PDX treatment with associated changes in gut microbiota composition and skeletal muscle mitochondrial function.
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This work was supported by a BBSRC industrial CASE studentship (BB/G017093/1) with Tate & Lyle PLC; Tommy’s Charity; European Union 7th Framework Programme (FP7/2007–2013) project EarlyNutrition under grant agreement No. 289346, Medical Research Council UK; Newton Fund (Partnership Project grant) RCUK-CONACYT Research Partnerships MR/N029259/1. Polydextrose was provided by Tate & Lyle. This study also received support from the NIHR Biomedical Research Centre based at Guy’s and St Thomas’ NHS Foundation Trust and King’s College London. The views expressed in this publication are those of the author and not necessarily those of the NHS, the NIHR, or the Department of Health.
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Maragkoudaki, X., Naylor, M., Papacleovoulou, G. et al. Supplementation with a prebiotic (polydextrose) in obese mouse pregnancy improves maternal glucose homeostasis and protects against offspring obesity. Int J Obes 44, 2382–2393 (2020). https://doi.org/10.1038/s41366-020-00682-5