Male obesity causes adipose mitochondrial dysfunction in F1 mouse progeny via a let-7-DICER axis - PubMed
4 hours ago
- #obesity
- #epigenetics
- #mitochondria
- Male obesity negatively affects gametic function and offspring metabolism.
- Obesity and weight loss in male mice reversibly alter metabolism and impair adipose mitochondrial function.
- Metabolic aberrations are transmitted to male offspring (F1), which show reduced mitochondrial gene expression.
- MicroRNAs let-7d/e are identified as epigenetic mediators induced in obese F0 sperm and F0/F1 adipose tissue.
- Let-7d/e silence the miRNA processor DICER1 and impair mitochondrial activity.
- Microinjecting let-7d/e into lean zygotes replicates the paternal obesity phenotype, causing glucose intolerance and mitochondrial gene suppression in offspring.
- Single-cell RNA sequencing shows let-7d/e impair oxidative metabolism in early embryos.
- Lifestyle-induced weight loss in obese males downregulates human HSA-LET-7D/E in semen, suggesting a conserved role for let-7 in metabolic health transmission.
- Findings indicate that microRNA let-7 in sperm reprograms offspring metabolism by modulating mitochondrial function during early development.