Maternal high calorie diet induces mitochondrial dysfunction and senescence phenotype in subcutaneous fat of newborn mice

Mitochondrial dysfunction, inflammation and senescence-like features are observed in adipose depots in aging and obesity. Herein, we evaluated how maternal high calorie diet (HCD) may impact on subcutaneous adipose tissue (sAT) of the newborn mice. Adult C57BL/6J mice were randomly divided in three groups: normal calorie diet (NCD), HCD and HCD supplemented with niacin 8 weeks before mating. Mothers and pups were then sacrificed and metabolic and molecular analyses were carried out on sAT. HCD induced mitochondria dysfunction in mothers without inflammation and senescence, whereas in pups we also revealed the occurrence of senescent phenotype. The mitochondrial dysfunction-associated senescence in pups was accompanied by a drop in NAD(+)/NADH ratio and alteration in the NAD(+)-dependent enzymes PARP1 and SIRT1. Importantly, maternal dietary supplementation with niacin during gestation and lactation restrained NAD(+)/NADH decrease imposed by HCD limiting inflammatory cytokine production and senescence phenotype in newborn sAT. Given the fundamental role of sAT in buffering nutrient overload and avoiding pathogenic ectopic fat accumulation, we suggest that NAD(+) boosting strategies during maternal HCD could be helpful in limiting sAT dysfunction in newborn.