ArticleCommunications biology2022
Omega-6 highly unsaturated fatty acids in Leydig cells facilitate male sex hormone production.
Article in Communications biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 8 papers.
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Who cites it
8 citing papers in PubMed, 16 citations in OpenAlex.
- The role of iron in normal and impaired testicular function.Andrology · 2026Review
- Article
- Effects of dietary supplementation with polyphenolic extracts from Lasia spinosa Thw. roots on reproductive performance in Guangxi Ma Roosters.Poultry science · 2026Article
- Quercetin upregulates steroid hormone biosynthesis to enhance reproductive performance in roosters.Poultry science · 2026Article
- Combined Effects of Dietary Soybean Lecithin With Vitamin C or Inositol on Growth, Gonadal Development, and Intestinal Microbiota in Longsnout Catfish.Aquaculture nutrition · 2026Article
- Gut microbiota is involved in male reproductive function: a review.Frontiers in microbiology · 2024Review
- GWAS-identified bipolar disorder risk allele in the FADS1/2 gene region links mood episodes and unsaturated fatty acid metabolism in mutant mice.Molecular psychiatry · 2023Article
- ACSL4-Mediated Ferroptosis and Its Potential Role in Central Nervous System Diseases and Injuries.International journal of molecular sciences · 2023Review
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Highly unsaturated fatty acids (HUFAs) are fatty acids with more than three double bonds in the molecule. Mammalian testes contain very high levels of omega-6 HUFAs compared with other tissues. However, the metabolic and biological significance of these HUFAs in the mammalian testis is poorly understood. Here we show that Leydig cells vigorously synthesize omega-6 HUFAs to facilitate male sex hormone production. In the testis, FADS2 (Fatty acid desaturase 2), the rate-limiting enzyme for HUFA biosynthesis, is highly expressed in Leydig cells. In this study, pharmacological and genetic inhibition of FADS2 drastically reduces the production of omega-6 HUFAs and male steroid hormones in Leydig cells; this reduction is significantly rescued by supplementation with omega-6 HUFAs. Mechanistically, hormone-sensitive lipase (HSL; also called LIPE), a lipase that supplies free cholesterol for steroid hormone production, preferentially hydrolyzes HUFA-containing cholesteryl esters as substrates. Taken together, our results demonstrate that Leydig cells highly express FADS2 to facilitate male steroid hormone production by accumulating omega-6 HUFA-containing cholesteryl esters, which serve as preferred substrates for HSL. These findings unveil a previously unrecognized importance of omega-6 HUFAs in the mammalian male reproductive system.
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