ROUX-en-Y gastric bypass surgery improves metabolic syndrome-related erectile dysfunction in mice via the IRS-1/PI3K/AKT/eNOS pathway.

Objective: Although many clinical studies have shown that ROUX-en-Y gastric bypass (RYGB) surgery significantly improves metabolic syndrome-related erectile dysfunction (MED), the role and mechanism are unclear.

Aim: In this study we used a mouse model to explore how RYGB improves MED induced by a high-fat diet (HFD).

Methods: We established a mouse model of metabolic syndrome by feeding an HFD for 16 weeks. The mice were randomly assigned to the standard chow diet (SCD), HFD, or RYGB groups. Body weight, fasting blood glucose, plasma insulin, and total plasma cholesterol were analyzed. Erectile responses were evaluated by determining the mean systolic blood pressure and the intracavernosal pressure (ICP). Penile histologic examination (Masson's trichrome and immunohistochemical stain) and Western blot were performed.

Result: Compared with the SCD group, the ICP in the sham group was significantly lower, and the ICP of the RYGB was significantly increased. Masson's trichrome and immunohistochemical staining showed that the content of endothelium and smooth muscle in the corpus cavernosum of mice with MED was significantly reduced. Western blot analysis showed a significant decrease in α-smooth muscle actin and a significant increase in osteopontin in penile tissue in the sham group, which was improved by RYGB surgery. Furthermore, RYGB significantly increased IRS-1/PI3K/Akt/eNOS phosphorylation.

Clinical translation: In this study we explored the mechanism of bariatric surgery to improve erectile dysfunction associated with metabolic syndrome and provided a theoretical basis for clinical research.

Strengths and limitations: First, we did not investigate the mechanism by which RYGB affects the IRS-1/PI3K/Akt/eNOS signaling pathway. Second, the effect of the IRS-1/PI3K/Akt/eNOS signaling pathway on the function of corpus cavernosum endothelial cells and smooth muscle cells remains to be investigated in cellular studies.

Conclusion: This study demonstrated that RYGB may not only improve metabolic parameters but also restore erectile function in MED patients. The mechanism of the therapeutic effect of RYGB may be reactivation of the IRS-1/PI3K/Akt/eNOS pathway.