A Mitochondrial Specific Antioxidant Reverses Metabolic Dysfunction and Fatty Liver Induced by Maternal Cigarette Smoke in Mice.

Gerard Li,Yik Lung Chan,Sonia Saad,Howard Vindin,Suporn Sukjamnong,Jacob George,Ayad G Anwer,Razia Zakarya,Hui Chen,Brian G Oliver,Matthew Padula

doi:10.3390/nu11071669

Abstract

Maternal smoking leads to glucose and lipid metabolic disorders and hepatic damage in the offspring, potentially due to mitochondrial oxidative stress. Mitoquinone mesylate (MitoQ) is a mitochondrial targeted antioxidant with high bioavailability. This study aimed to examine the impact of maternal cigarette smoke exposure (SE) on offspring’s metabolic profile and hepatic damage, and whether maternal MitoQ supplementation during gestation can affect these changes. Female Balb/c mice (eight weeks) were either exposed to air or SE for six weeks prior to mating and throughout gestation and lactation. A subset of the SE dams were supplied with MitoQ in the drinking water (500 µmol/L) during gestation and lactation. Intraperitoneal glucose tolerance test was performed in the male offspring at 12 weeks and the livers and plasma were collected at 13 weeks. Maternal SE induced glucose intolerance, hepatic steatosis, mitochondrial oxidative stress and related damage in the adult offspring. Maternal MitoQ supplementation reduced hepatic mitochondrial oxidative stress and improved markers of mitophagy and mitochondrial biogenesis. This may restore hepatic mitochondrial health and was associated with an amelioration of glucose intolerance, hepatic steatosis and pathological changes induced by maternal SE. MitoQ supplementation may potentially prevent metabolic dysfunction and hepatic pathology induced by intrauterine SE.

Highlights

Tobacco cigarette smoking during pregnancy has been associated with an increased risk of metabolic disorders in the offspring, especially type 2 diabetes in adulthood [1]
Male offspring from smoke exposure (SE) mothers had lower birth weight compared to male offspring from Sham mothers, which was normalised when MitoQ was administered to the SE mothers (p < 0.01, SE + MQ vs. SE, Table 1)
At 13 weeks, SE offspring remained smaller compared to the Sham offspring (p < 0.05), which was reversed in the SE + MQ group (p < 0.01, Table 1)

Summary

Introduction

Tobacco cigarette smoking during pregnancy has been associated with an increased risk of metabolic disorders in the offspring, especially type 2 diabetes in adulthood [1]. In utero smoke exposure (SE) increases oxidative stress and damage in the offspring’s liver [2], which can lead to mitochondrial dysfunction. The imbalance between excessive ROS and antioxidant capacity leads to oxidative stress and mitochondrial damage. Adaptive mechanisms respond to damaged mitochondria through the processes of mitophagy and mitochondrial biogenesis [4]. Hepatic mitochondrial dysfunction (increased oxidative stress or impaired adaptive mechanisms) can lead to glucose intolerance and triglyceride accumulation, which could underlie the development of type 2 diabetes and non-alcoholic fatty liver disease [5]. Increasing evidence, including our own work, has suggested that in utero SE can induce mitochondrial damage in multiple organs, increasing mitochondrial ROS output and impairing metabolic function [6,7,8,9].

Objectives

Methods

Results