Supplementation with a prebiotic (polydextrose) in obese mouse pregnancy improves maternal glucose homeostasis and protects against offspring obesity.

OBJECTIVES: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 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.

Maternal obesity programs offspring nonalcoholic fatty liver disease by innate immune dysfunction in mice.

UNLABELLED: The global prevalence of obesity-induced liver disease (nonalcoholic fatty liver disease; NAFLD) is rising. Suggested causes include a role for in utero influences of maternal obesity compounded by the availability of energy-dense foods throughout postnatal life. Using a physiologically relevant model, we investigated the role of the innate immune system in liver injury induced by maternal obesity followed by a postnatal obesogenic diet. Female C57BL/6J mice were fed a standard or obesogenic diet before and throughout pregnancy and during lactation. Female offspring were weaned onto a standard or obesogenic diet at 3 weeks postpartum. Biochemical and histological indicators of dysmetabolism, NAFLD and fibrosis, analysis of profibrotic pathways, liver innate immune cells, and reactive oxygen species (ROS) were investigated at 3, 6, and 12 months. Female offspring exposed to a postweaning obesogenic diet (OffCon-OD) demonstrated evidence of liver injury, which was exacerbated by previous exposure to maternal obesity (OffOb-OD), as demonstrated by raised alanine aminotransferase, hepatic triglycerides, and hepatic expression of interleukin (IL)-6, tumor necrosis factor alpha, transforming growth factor beta, alpha smooth muscle actin, and collagen (P < 0.01). Histological evidence of hepatosteatosis and a more-robust NAFLD phenotype with hepatic fibrosis was observed at 12 months in OffOb-OD. A role for the innate immune system was indicated by increased Kupffer cell numbers with impaired phagocytic function and raised ROS synthesis (P < 0.01), together with reduced natural killer T cells and raised interleukin (IL)-12 and IL-18. CONCLUSION: Maternal obesity in the context of a postnatal hypercalorific obesogenic diet aggressively programs offspring NAFLD associated with innate immune dysfunction, resulting in a comprehensive phenotype that accurately reflects the human disease.