PMID- 33378994
OWN - NLM
STAT- MEDLINE
DCOM- 20210224
LR  - 20240226
IS  - 1950-6007 (Electronic)
IS  - 0753-3322 (Linking)
VI  - 133
DP  - 2021 Jan
TI  - N-acetylcysteine protects neonatal mice from ventricular hypertrophy induced by 
      maternal obesity in a sex-specific manner.
PG  - 110989
LID - S0753-3322(20)31181-1 [pii]
LID - 10.1016/j.biopha.2020.110989 [doi]
AB  - BACKGROUND: Maternal obesity induces adverse cardiac programming in offspring, 
      and effective interventions are needed to prevent cardiovascular ill-health. 
      Herein we hypothesized that exposure to maternal obesogenic diet-induced obesity 
      in mice results in left ventricular remodelling and hypertrophy in early 
      childhood, and that maternal N-acetylcysteine (NAC) treatment alleviates these 
      effects in a sex-dependent manner. METHODS AND RESULTS: The maternal obesity was 
      induced in mice by the consumption of a Western diet accompanied by a 20 % 
      sucrose solution. To determine the effect of NAC on the cardiac outcomes induced 
      by maternal obesity, obese dams were continuously exposed to the obesogenic diet, 
      with or without the oral NAC treatment during pregnancy. Left ventricular 
      remodelling and hypertrophy occurred as early as 7 days after birth in the male 
      offspring of obese dams (O-OB) compared with controls (O-CO). An over-expression 
      of key genes and markers related to cardiac fibrosis accompanied by more 
      disorganized myofibrils was observed in the hearts of neonatal male O-OB mice. 
      When we next evaluated the level of oxidative stress in the hearts of neonatal 
      mice, the activity of enzymatic antioxidants declined and expression of NOX 
      enzyme complex was up-regulated in O-OB offspring hearts, but was normal in the 
      offspring of NAC treated mice (O-OB/NAC). Maternal obesity also activated cardiac 
      Akt and mammalian target of rapamycin (mTOR) signalling in offspring, and NAC 
      treatment restored offspring cardiac Akt-mTOR signalling to normal irrespective 
      of sex. NAC treatment did not prevent cardiomyocyte hypertrophy but did alleviate 
      increased heart weight, interventricular septal thickness, and collagen content 
      in male O-OB/NAC pups. CONCLUSIONS: Collectively, our results indicated that NAC 
      blunted cardiac fibrosis and related ventricular hypertrophy of male neonatal 
      offspring in the setting of maternal obesity, potentially acting by reducing 
      oxidative stress. The present study provides a basis for investigating the role 
      of NAC in nutrition-related cardiac programming.
CI  - Copyright (c) 2020 The Authors. Published by Elsevier Masson SAS.. All rights 
      reserved.
FAU - Zhang, Jialing
AU  - Zhang J
AD  - Cardiovascular Center, Children's Hospital of Fudan University, Shanghai, China; 
      MOH Key Laboratory of Neonatal Diseases at Children's Hospital, Fudan University, 
      Shanghai, China.
FAU - Cao, Li
AU  - Cao L
AD  - Ultrasound Department, Obstetrics and Gynecology Hospital of Fudan University, 
      Shanghai, China.
FAU - Tan, Yanfeng
AU  - Tan Y
AD  - Institute of Pediatrics, Children's Hospital of Fudan University, Shanghai, 
      China.
FAU - Zheng, Yuanzheng
AU  - Zheng Y
AD  - Cardiovascular Center, Children's Hospital of Fudan University, Shanghai, China; 
      MOH Key Laboratory of Neonatal Diseases at Children's Hospital, Fudan University, 
      Shanghai, China.
FAU - Gui, Yonghao
AU  - Gui Y
AD  - Cardiovascular Center, Children's Hospital of Fudan University, Shanghai, China; 
      MOH Key Laboratory of Neonatal Diseases at Children's Hospital, Fudan University, 
      Shanghai, China. Electronic address: yhgui@shmu.edu.cn.
LA  - eng
PT  - Journal Article
DEP - 20201208
PL  - France
TA  - Biomed Pharmacother
JT  - Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie
JID - 8213295
RN  - 0 (Antioxidants)
RN  - WYQ7N0BPYC (Acetylcysteine)
SB  - IM
MH  - Acetylcysteine/*pharmacology
MH  - Animal Nutritional Physiological Phenomena
MH  - Animals
MH  - Animals, Newborn
MH  - Antioxidants/*pharmacology
MH  - Disease Models, Animal
MH  - Female
MH  - Fibrosis
MH  - Heart Ventricles/*drug effects/metabolism/physiopathology
MH  - Hypertrophy, Left Ventricular/etiology/metabolism/physiopathology/*prevention & 
      control
MH  - Male
MH  - Maternal Nutritional Physiological Phenomena
MH  - Mice, Inbred C57BL
MH  - Obesity, Maternal/*complications/physiopathology
MH  - Oxidative Stress/*drug effects
MH  - Pregnancy
MH  - Prenatal Exposure Delayed Effects
MH  - Sex Factors
MH  - Ventricular Function, Left/*drug effects
MH  - Ventricular Remodeling/*drug effects
MH  - Mice
OTO - NOTNLM
OT  - Maternal obesity
OT  - N-acetylcysteine
OT  - Oxidative stress
OT  - Sex difference
OT  - Ventricular hypertrophy
EDAT- 2021/01/01 06:00
MHDA- 2021/02/25 06:00
CRDT- 2020/12/31 01:01
PHST- 2020/07/14 00:00 [received]
PHST- 2020/10/28 00:00 [revised]
PHST- 2020/11/05 00:00 [accepted]
PHST- 2020/12/31 01:01 [entrez]
PHST- 2021/01/01 06:00 [pubmed]
PHST- 2021/02/25 06:00 [medline]
AID - S0753-3322(20)31181-1 [pii]
AID - 10.1016/j.biopha.2020.110989 [doi]
PST - ppublish
SO  - Biomed Pharmacother. 2021 Jan;133:110989. doi: 10.1016/j.biopha.2020.110989. Epub 
      2020 Dec 8.