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

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.

Role of mitochondrial quality control in the pathogenesis of nonalcoholic fatty liver disease

“…Attenuation of mitochondrial oxidative stress is a promising strategy to reduce mitochondrial damage and slow the progression of NAFLD. Administration of mitoquinone mesylate (MitoQ), a mitochondrial-targeted antioxidant with high bioavailability, restores hepatic mitochondrial functions and ameliorates glucose intolerance and hepatic steatosis [61][62][63]. Antioxidant foods including blueberry juice and probiotics significantly reduce NAFLD-induced mitochondrial swelling and hepatic necrosis by restoring the mitochondrial respiratory chain function and suppressing the production of ROS [64].…”

E‐cigarettes damage the liver and alter nutrient metabolism in pregnant mice and their offspring

“…Liver lipids were extracted using the Folch method, 13 as previously described. 10 Plasma, liver extracts, and glycerol standards (Sigma-Aldrich, St. Louis, MO) were incubated with the triacylglycerol reagent (Roche Diagnostics, Basel, Switzerland) using an in-house assay. 12 Plasma nonesterified free fatty acid (NEFA) concentrations were measured using a NEFA kit (WAKO, Osaka, Japan).…”

“…In mouse models of maternal smoking during pregnancy, intrauterine tobacco smoke exposure impairs fetal development and increases mitochondrial-derived OS in the liver in adulthood. 10 This is closely related to increased inflammation, fatty liver changes, and systemic lipid and glucose metabolic disorders in the offspring. 10,11 Given the inflammatory response and OS induced by maternal e-vapor exposure in the lungs, brain, and kidneys, [6][7][8][9] we hypothesized that long-term maternal e-vapor exposure might lead to similar disorders in the liver, resulting in glucose and lipid metabolic changes in both the dams and their offspring.…”

“…10 This is closely related to increased inflammation, fatty liver changes, and systemic lipid and glucose metabolic disorders in the offspring. 10,11 Given the inflammatory response and OS induced by maternal e-vapor exposure in the lungs, brain, and kidneys, [6][7][8][9] we hypothesized that long-term maternal e-vapor exposure might lead to similar disorders in the liver, resulting in glucose and lipid metabolic changes in both the dams and their offspring. Therefore, the aims of our study were to investigate the impact of maternal e-vapor exposure before gestation and during pregnancy on hepatic metabolic markers, OS, inflammation, and mitochondrial health in both the dams and their male offspring.…”

“…Only male offspring were examined because the metabolic responses to maternal smoking between male and female offspring are similar. 10,11…”