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Maternal high calorie diet induces mitochondrial dysfunction and senescence phenotype in subcutaneous fat of newborn
Daniele Lettieri-Barbato1,2, Fabiana D'Angelo1, Francesca Sciarretta1
1Department of Biology, University of Rome Tor Vergata, Rome, Italy.
Insights
Maternal high-calorie diets harm newborn adipose tissue, causing mitochondrial dysfunction and senescence. Niacin supplementation during pregnancy and lactation protected newborns from these effects by boosting NAD+ levels.
Area of Science:
- Metabolic Research
- Developmental Biology
- Nutritional Science
Background:
- Aging and obesity are linked to mitochondrial dysfunction, inflammation, and senescence in adipose tissue.
- Maternal diet during gestation and lactation significantly influences offspring metabolic health.
- Subcutaneous adipose tissue (sAT) plays a crucial role in nutrient buffering and preventing ectopic fat accumulation.
Purpose of the Study:
- To investigate the impact of maternal high-calorie diet (HCD) on the subcutaneous adipose tissue (sAT) of newborn mice.
- To assess the protective effects of niacin supplementation on HCD-induced alterations in newborn sAT.
- To explore the role of NAD+ metabolism in HCD-induced sAT dysfunction in offspring.
Main Methods:
- Adult female mice were fed normal calorie diet (NCD), HCD, or HCD with niacin before and during mating.
- Metabolic and molecular analyses were performed on the sAT of mothers and their newborn pups.
- Key parameters assessed included mitochondrial function, inflammation, senescence markers, and NAD+/NADH ratio.
Main Results:
- Maternal HCD induced mitochondrial dysfunction in mothers but not inflammation or senescence.
- Newborns exposed to maternal HCD exhibited senescence phenotype in sAT, linked to decreased NAD+/NADH ratio and altered PARP1/SIRT1 activity.
- Maternal niacin supplementation mitigated HCD-induced NAD+/NADH decrease, reduced inflammatory cytokines, and prevented senescence in newborn sAT.
Conclusions:
- Maternal HCD negatively impacts newborn sAT, inducing mitochondrial dysfunction and senescence via altered NAD+ metabolism.
- Niacin supplementation during gestation and lactation can counteract these detrimental effects.
- NAD+ boosting strategies represent a potential therapeutic approach to prevent sAT dysfunction in offspring of mothers with HCD.
Abstract:
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.
