Functional Impairment in the Corpus Cavernosum Related to a High Fat Diet is Prevented in Toll‐Like Receptor 9 Mutant Mice

Abstract

High fat diets lead to obesity and trigger inflammatory processes which are associated with an increase in the toll‐like receptor 9 (TLR9) signaling pathway in rodent models of non‐alcoholic fatty liver disease. Furthermore, TLR9 signaling plays a role in inflammation regulation of adipose tissue in obesity and metabolic syndrome. Erectile dysfunction (ED) has been correlated with increased inflammatory mediators. Since obesity induces ED, we hypothesize that the impaired function in the corpus cavernosum may be related to an increase in the TLR9 signaling in obese mice. The aim of this study was to evaluate the relaxation and contractile responses of the corpus cavernosum of wild type and TLR9 mutant mice made obese by a high fat diet. Four week old male C57BL/6 and TLR9 mutant mice were fed a high fat diet for 12 weeks. The corpus cavernosum was then mounted on strip myograph for functional evaluation. The contractile and relaxation responses of the corpus cavernosum were evaluated by electrical field stimulation (EFS) and concentration response curves to acetylcholine and phenylephrine. We observed that the relaxation induced by EFS was decreased in wild type obese mice. Deletion of TLR9 prevented this decrease. On the other hand, EFS‐induced contraction at 8 Hz was higher in the corpus cavernosum of obese wild type mice. However, this increase was prevented in TLR9 mutant mice. Furthermore, we observed that the contraction induced by KCl solution (120 mM) and maximal contraction induced by phenylephrine tended to be increased in wild type obese mice only. No changes were observed in the relaxation induced by acetylcholine or in the potency of phenylephrine. In conclusion, these data suggest that TLR9 signaling pathway contributes to erectile dysfunction induced by a high fat diet.Support or Funding InformationNIH: NHLBI001961FAPESP: 2016/20592‐8This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.