Maternal Obesity Programs the Premature Aging of Rat Offspring Liver Mitochondrial Electron Transport Chain Genes in...

Area of Science:

• Biochemistry
• Molecular Biology
• Metabolic Research

Background:

• Maternal obesity is a growing concern with potential long-term health implications for offspring.
• The impact of maternal diet on offspring liver mitochondria, sirtuins, and antioxidant enzymes requires further investigation, particularly concerning sex and age differences.

Purpose of the Study:

• To investigate the sex- and age-dependent effects of maternal high-fat diet (maternal obesity) on the hepatic mitochondrial electron transport chain (ETC), sirtuins, and antioxidant enzymes in offspring.
• To determine if maternal obesity accelerates aging processes in the offspring liver.

Main Methods:

• Wistar rats were fed control or high-fat diets during gestation and lactation.
• Offspring livers were collected at young (110 postnatal days) and old (650 postnatal days) ages for RNA-sequencing and immunohistochemistry.
• Differential gene expression analysis and KEGG pathway enrichment were performed.

Main Results:

• Male offspring livers exhibited more down-regulated differentially expressed genes (DEGs) due to maternal obesity and aging compared to females.
• Maternal obesity led to premature aging in male offspring, indicated by common DEGs and altered KEGG pathways.
• Down-regulation of ETC complexes, sirtuin2, sirtuin3, sod-1, and catalase genes and proteins was observed in male offspring, with females showing effects only at older ages.

Conclusions:

• Maternal obesity accelerates age-associated down-regulation of hepatic ETC gene expression in male offspring.
• This leads to sex-dependent oxidative stress, premature aging, and metabolic dysfunction in male offspring.
• The liver's mitochondrial function and antioxidant capacity are significantly impacted by maternal obesity in a sex-specific manner.