ACUTE VS. CHRONIC RESPONSE OF SREBP2 PATHWAY TO HFD IN RABBIT TESTICLES

AVENA ALVAREZ, MARÍA VIRGINIA; MONCLUS, MARÍA; FUNES, ABI; CRESCITELI, J; FORNÉS, MIGUEL; COLOMBO, REGINA; ROLDAN, ADRIAN; SAEZ LANCELLOTTI, EMILCE

SAN LUIS

Congreso; IV REUNION CONJUNTA DE SOCIEDADES DE BIOLOGÍA DE LA REPUBLICA ARGENTINA; 2020

SOCIEDAD DE BIOLOGÍA DE CUYO

Male fertility has been shown to be dependent on cholesterol (chol) homeostasis. Chol is essential for testosterone synthesis and spermatogenesis, but for the proper functioning of the testicles, the chol should be maintained in an ideal ratio. We have previously shown that rabbits under a high fat diet (HFD) present low seminal quality related to an overload of cholesterol in cells of the seminiferous tubule. The aim of this work was to study whether the molecular pathway that regulates intracellular chol, the sterol binding element regulatory protein (SREBP) pathway, is affected in the testicles of animals under a HFD. To investigate this, we took advantage of the non-obese hypercholesterolemic model in New Zealand rabbits (HCR) that display poor seminal quality. The expression of SREBP-2 was studied under acute (HCR ≤ 6M, between 3 and 6 months of diet) and chronic (HCR ≥ 12M, between 12 and 24 months of diet) intake of HFD (14% bovine grase w/w) by RT-PCR, western blot and immunofluorescence. Our findings showed that fat consumption promoted down regulation of the SREBP-2 pathway in the testicle at 6 months, but upregulation after a chronic period. This was consistent with a load of testicular cholesterol, assessed by Filipin staining. In addition, it was possible to observe the subcellular location of the protein SREBP-2 in testicular tissue, detected by indirect immunofluorescence. However, both blood lipid alterations and seminal deleterious changes were observed from the acute intake period. In conclusion, the pathway that regulates chol levels in the testicle is sensitive to dietary fat, and behaves differently depending on the duration of the diet: it has a short-term protective effect, but is deregulated in the long term, ultimately leading to a detrimental situation, related to poor seminal quality.