J Biomed Transl Res.  2022 Dec;23(4):151-162. 10.12729/jbtr.2022.23.4.151.

Effects of high-fat diet on the testicular function of sirtuin 1 (SIRT1) knockout male mice

• Chandanee MR
• Lee SM
• Yi YJ

• KMID: 2538510
• DOI: http://doi.org/10.12729/jbtr.2022.23.4.151

Abstract

Sirtuin 1 (SIRT1), the most conserved nicotinamide adenine dinucleotide-dependent protein deacetylase, is involved in the regulation of energy metabolism, genomic stability, and development. SIRT1 knockout (SIRT1) mice exhibit decreased energy expenditure and hypersen- sitivity to a high-fat diet (HFD). SIRT1 deficiency in the testis has also been shown to cause male infertility in animal models. Therefore, the present study was conducted to examine the alteration of the testicular function of SIRT1 mice on HFD. Six-week-old mice were fed ad libitum as wild type (WT) and SIRT1 male mice with either a control diet or with HFD for 32 weeks and then were sacrificed. The levels of biomarkers for hepatotoxicity, sex hormones, and cytokines were analyzed in the serum and blood-testis barrier, and the sperm morpholo-gy was examined in the testis and epididymal spermatozoa. Interestingly, an enlargement of seminal vesicles was observed in the SIRT1 mice fed with HFD. A significantly higher level of hepatotoxicity was also seen in these mice. The concentration of serum testosterone in-creased in HFD-fed SIRT1 mice compared to the controls. The levels of interleukin-1β and TNF-α increased in both HFD-fed WT and SIRT1 mice. In RT-PCR, the m RNA expression of tight junction protein 2 and claudin 3 significantly decreased in HFD-fed SIRT1 compared to those of the controls. Degenerative spermatocytes and spermatids were detected in the HFD-fed SIRT1 mice testicular section. Sperm motility decreased in WT and SIRT1 with HFD feeding, and sperm concentration decreased significantly in WT-HFD and SIRT1 mice with or without HFD feeding. Taken together, HFD can alter energy and steroid metabolism in SIRT1-deficient mice, which can lead to imbalances in motility and production of sperm and testosterone that can result in male reproductive disorders.

Keyword

diet; high-fat; high-fat; spermatogenesis; male; mice