Research Article: Perinatal phlorizin alleviates maternal high-fat diet-induced metabolic syndrome in female mouse offspring and is associated with modulation of the gut microbiota
Abstract:
Maternal obesity induces transgenerational metabolic syndrome (MS). The role of phlorizin (PHZ) in improving MS has been confirmed; however, the transgenerational metabolic benefits of PHZ in female offspring remain unclear. This study aimed to investigate whether perinatal PHZ intake could mitigate the adverse metabolic effects of maternal high-fat diet (HFD) in female offspring and to elucidate the role of the gut microbiota in mediating these transgenerational effects.
C57BL/6 mice with maternal HFD ± perinatal PHZ (0.8 g/kg diet) intervention were used. After weaning, Female offspring’s glucolipid metabolism, gut barrier, gut microbiota, and SCFAs were analyzed. Obesogenic dietary challenge and fecal microbiota transplantation (FMT) were implemented to verify microbiota mediation.
Maternal HFD induces metabolic abnormalities in female offspring, characterized by disrupted glucolipid metabolism during weaning and mild obesity. In adulthood, although these offspring did not display overt obesity, they exhibited gut microbial dysbiosis (increase Firmicutes/Bacteroidetes ratio and pro-inflammatory bacteria), accompanied by insulin resistance and impaired intestinal barrier function, along with a significantly increased obesity susceptibility. Maternal PHZ co-intervention ameliorated MS and restored gut microbial balance in adulthood, increased the abundance of SCFA-producing bacteria ( Akkermansia muciniphila and Blautia sp.), elevated fecal SCFAs and serum GLP1/2 levels, improved gut barrier integrity, alleviated inflammatory conditions, and reduced obesity susceptibility. To eliminate the protective effect of estrogen metabolism, antibiotic-treated (ABX) male mice were selected as the recipients for FMT. ABX male mice receiving FMT from PHZ-intervened female offspring could attenuate MS induced by receiving FMT from maternal HFD offspring via the gut microbiota–SCFA pathway.
Our findings suggested that maternal PHZ alleviates maternal HFD-induced transgenerational metabolic dysfunction in female offspring and is associated with modulation of the gut microbiota, positioning PHZ as a promising functional food component with transgenerational metabolic protective potential.
Introduction:
Maternal obesity induces transgenerational metabolic syndrome (MS). The role of phlorizin (PHZ) in improving MS has been confirmed; however, the transgenerational metabolic benefits of PHZ in female offspring remain unclear. This study aimed to investigate whether perinatal PHZ intake could mitigate the adverse metabolic effects of maternal high-fat diet (HFD) in female offspring and to elucidate the role of the gut microbiota in mediating these transgenerational effects.
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