Obesity induced by a high-fat diet changes p62 protein levels in mouse reproductive organs

• Published in: Journal of molecular histology 2025-02, Vol.56 (1), p.13
• Main Authors: Bozdemir, Nazlican, Kablan, Tuba, Sukur, Gozde, Cinar, Ozgur, Uysal, Fatma
• Format: Article
• Language: English
• Subjects: Animals; Autophagy; Biomedical and Life Sciences; Biomedicine; Cell Biology; Corpus luteum; Developmental Biology; Diet, High-Fat - adverse effects; Epithelium; Female; Fetuses; Gametes; Gene expression; High fat diet; High protein diet; Homeostasis; Infertility; Kelch-Like ECH-Associated Protein 1 - genetics; Kelch-Like ECH-Associated Protein 1 - metabolism; Life Sciences; Male; Mice; Mice, Inbred C57BL; Myometrium; NRF2 protein; Obesity; Obesity - etiology; Obesity - metabolism; Original Paper; Ovaries; Ovary - metabolism; Ovary - pathology; Oxidative Stress; p62 Protein; Proteins; Reproductive organs; Risk factors; Sequestosome-1 Protein - genetics; Sequestosome-1 Protein - metabolism; Spermatocytes; Stroma; Testis - metabolism; Uterus; Uterus - metabolism
• ISSN: 1567-2379; 1567-2387; 1567-2387
• DOI: 10.1007/s10735-024-10310-5

Obesity is one of the major risk factor for infertility since it causes decreased quality and quantity of gametes and a disrupted uterine environment which might result in miscarriage, stillbirth, and fetal abnormal growth. Obesity induces oxidative stress which is strongly associated with infertility. The clearing of oxidative stress by autophagy is maintained through the p62/ Keap1/Nrf2 pathway. In this pathway, oxidative stress induces p62 for binding to Keap1, thereby Keap1 cannot bind to the Nrf2 transcription factor. Then, Nrf2 translocates into the nucleus and initiates antioxidant-related gene expression. While p62, bound to Keap1, acts as an adaptor protein between autophagosome and damaged substrates which needs to be degraded for homeostasis. Up to date, obesity is strongly linked to abnormal autophagy activity. However, p62 protein expression has not been investigated in the obese ovary, testis, and uterus in detail. Thus, in the present study, we aimed to evaluate the effects of a high-fat diet (HFD)-induced obesity on p62 protein levels of the ovary, testis, and uterus in mice. Our results demonstrated that the p62 expression level was significantly altered by HFD in uterine glands, epithelium, myometrium, and stroma, and in the ovarian corpus luteum, testicular spermatogonium and spermatocytes.