Obesity can lead to cardiovascular disease, diabetes, and erectile dysfunction (ED), which decreases overall quality of life. Mechanisms responsible for obesity-induced ED are unknown. Current mouse models of high-fat diet (HFD)-induced obesity yield conflicting results. Genetic variants among common “wild type” strains may explain contradictory data. Adult male C57BL/6N and 6J mice were fed a 45% HFD for 12 weeks. Weekly food intake, weight gain, and body-fat percentage were measured. After 12 weeks, ex vivo vascular reactivity was measured in aortas, internal pudendal arteries, and penises. We assessed smooth muscle contractility, endothelial-dependent and -independent relaxation, and penile neurotransmitter-mediated relaxation. C57BL/6N mice developed greater obesity and glucose sensitivity compared to C57BL/6J mice. Aortas from both strains that fed a HFD had decreased contraction, yet contraction was unchanged in HFD pudendal arteries and penises. Interestingly, endothelial-dependent and -independent relaxation was unchanged in both systemic and penile vasculature. Likewise, HFD did not impair penile neurotransmitter-mediated relaxation. Both strains fed 12 weeks of HFD-developed obese phenotypes. However, HFD did not impair pre-penile or penile smooth muscle vasoreactivity as demonstrated in previous studies, suggesting that this preclinical model does not accurately represent the clinical phenotype of obesity-induced ED.
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Funding was provided to MRO by a research grant from the Sexual Medicine Society of North America and by NIDDK K12-DK100024 Grant, and to JLH by NIDDK Diabetic Complications Consortium (DiaComp, www.diacomp.org), Grant DK076169 and DK115255.
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Odom, M.R., Hunt, T.C., Pak, E.S. et al. High-fat diet induces obesity in adult mice but fails to develop pre-penile and penile vascular dysfunction. Int J Impot Res (2021). https://doi.org/10.1038/s41443-021-00440-9