Omega-6 highly unsaturated fatty acids in Leydig cells facilitate male sex hormone production View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2022-09-21

AUTHORS

Keiken Ri, Hyeon-Cheol Lee-Okada, Takehiko Yokomizo

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. More... »

PAGES

1001

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/s42003-022-03972-y

DOI

http://dx.doi.org/10.1038/s42003-022-03972-y

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1151184546

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/36131086


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