Maternal Isocaloric High‐Fat Diet Induces Liver Mitochondria Maladaptations and Homeostatic Disturbances Intensifying Mitochondria Damage in Response to Fructose Intake in Adult Male Rat Offspring

Abstract

Scope: Perinatal maternal obesity and excessive fructose consumption have been associated with liver metabolic diseases. The study investigates whether moderate maternal high-fat diet affects the liver mitochondria responses to fructose intake in adult offspring. Methods and Results: Wistar female rats have received a standard diet (mSTD) or high-fat diet (mHFD) (9% and 28.6% fat, respectively), before mating until the end of lactation. Male offspring were fed standard diet from weaning to adulthood and received water or fructose-drinking water (15%) from 120 to 150 days old. Fructose induces liver mitochondrial ultrastructural alterations with higher intensity in mHFD offspring, accompanied by reduced autophagy markers. Isolated mitochondria respirometry shows unaltered ATP-coupled oxygen consumption with increased Atp5f1b mRNA only in mHFD offspring. Fructose increases basal respiration and encoding complex I-III mRNA, only in mSTD offspring. Uncoupled respiration is lower in mHFD mitochondria that are unable to exhibit fructose-induced increase Ucp2 mRNA. Fructose decreases antioxidative defense markers, increases unfolded protein response and insulin resistance only in mHFD offspring without fructose-induced hepatic lipid accumulation. Conclusion: Mitochondrial dysfunction and homeostatic disturbances in response to fructose are early events evidencing the higher risk of fructose damage in the liver of adult offspring from dams fed an isocaloric moderate high-fat diet.

Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High‐Fat Diet

“…[13] In addition, mHFD triggers hepatic lipid accumulation associated with oxidative stress at adulthood. [10,11,14] The data suggest an early origin of liver abnormalities in males.…”

“…Liver fragments were processed as previously described, [10,14] and were detailed in the Supplementary information. Ultrathin sections were analyzed in the JEOL JEM 1011 transmission electron microscope.…”

“…The total number per area (μm 2 ) data were quantified and the damaged mitochondrial percentage was evaluated by analyzing the membranes disruption, mitochondrial cristae morphology, and the matrix electron density. [14,33]…”

Guava Leaf Extract Suppresses Fructose Mediated Non-Alcoholic Fatty Liver Disease in Growing Rats

“…Thus, the maladaptive consequences stimulate inflammation and mitochondrial dysfunction that together lead to insulin resistance. 49 , 50 On this basis, freshly isolated murine hepatocytes were exposed to conditions that mimic insulin resistance (1mM fructose, FC2) and assessed for markers of mitochondrial dysfunction and oxidative stress.…”

Muscle FOXO-Specific Overexpression and Endurance Exercise Protect Skeletal Muscle and Heart from Defects Caused by a High-Fat Diet in Young Drosophila

“…Moreover, a HFD can down-regulated the triglyceride lipase gene (homologous to Drosophila brummer) and up-regulated the fatty acid synthase gene (homologous to Drosophila FAS) [4][5][6][7][8], which is an important molecular mechanism leading to the continuous accumulation of triglyceride in the body. What's more, a HFD can inhibit Sirt1/FOXO pathway and induce mitochondrial synthesis defects and mitochondrial dysfunction in liver, heart, and muscle [9][10][11][12][13][14][15]. However, the role of FOXO gene in HSD-induced (High Salt Diet) skeletal muscle and myocardial damage is poorly understood.…”