Paternal transgenerational epigenetic effects: high fat diet induced obesity alters miRNA expression in F1 and F2 C57BL/6 male mice


Satir-Basaran G., Rassoulzadegan M., Cumaoglu A.

MOLECULAR GENETICS AND GENOMICS, cilt.300, sa.1, 2025 (SCI-Expanded, Scopus) identifier identifier identifier

  • Yayın Türü: Makale / Tam Makale
  • Cilt numarası: 300 Sayı: 1
  • Basım Tarihi: 2025
  • Doi Numarası: 10.1007/s00438-025-02318-7
  • Dergi Adı: MOLECULAR GENETICS AND GENOMICS
  • Derginin Tarandığı İndeksler: Science Citation Index Expanded (SCI-EXPANDED), Scopus, BIOSIS, Chemical Abstracts Core, EMBASE, MEDLINE
  • Anahtar Kelimeler: Epigenetic, HFD, ND, miRNA, Obesity, Inheritance
  • Erciyes Üniversitesi Adresli: Evet

Özet

Paternal obesity affects offspring's metabolic health. Genetic and environmental factors lead to metabolic dysfunction and obesity, a condition affecting future generations worldwide. The reasons for this condition's transgenerational transmission are important. The mechanisms of RNA-mediated heritability remain unclear, and there is limited knowledge about the effects of paternal exposure. Recent studies indicate that microRNAs (miRNAs) regulate metabolic processes that alter or maintain metabolic homeostasis and energy balance in obesity. Considering the increase in global obesity rates, this study aimed to investigate the impact of paternal influence on metabolic health through the epigenetic mechanism in normal diet (ND) fed F1 and F2 offspring of high fat diet (HFD) induced C57BL/6 male mice. Paternal obesity can transmit epigenetic changes in germ cells to subsequent generations, causing adipose tissue remodeling in offspring. To investigate the effects of HFD exposure in epididymal adipose tissue of male mouse offspring, miRNA expression levels were determined by qRT-PCR and protein levels by western blotting. In addition, paternal HFD exposure had significantly increased the expression of adipogenic proteins involved in lipid metabolism in epididymal adipose tissue. Expression levels of miR-199a-5p significantly increased in offspring. This study emphasizes the significance of paternal miRNAs in transmitting diet-induced phenotypes and metabolic adaptations to offspring. The results imply that metabolic disorders in fathers may be heritable and that lifestyle may serve as molecular biomarkers for epigenetic changes in the development and subsequent health of offspring.