TY - JOUR
T1 - Maternal high calorie diet induces mitochondrial dysfunction and senescence phenotype in subcutaneous fat of newborn mice
AU - Lettieri-Barbato, Daniele
AU - D'Angelo, Fabiana
AU - Sciarretta, Francesca
AU - Tatulli, Giuseppe
AU - Tortolici, Flavia
AU - Ciriolo, Maria Rosa
AU - Aquilano, Katia
PY - 2017/1/1
Y1 - 2017/1/1
N2 - 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.
AB - 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.
KW - Adipocytes
KW - Aging
KW - Gerotarget
KW - Inflammation
KW - NAD
KW - Senescence
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UR - http://www.scopus.com/inward/citedby.url?scp=85031030310&partnerID=8YFLogxK
U2 - 10.18632/oncotarget.19948
DO - 10.18632/oncotarget.19948
M3 - Article
AN - SCOPUS:85031030310
VL - 8
SP - 83407
EP - 83418
JO - Oncotarget
JF - Oncotarget
SN - 1949-2553
IS - 48
ER -