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High-fat diet induces obesity in adult mice but fails to develop pre-penile and penile vascular dysfunction


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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Fig. 1: Adult 6J and 6N mice fed a 12-week HFD that exhibit unique metabolic phenotypes.
Fig. 2: HFD reduces KCl contractions exclusively in 6N aortas.
Fig. 3: Aortic adrenergic contractility decreases following a 12-week HFD.
Fig. 4: A modest HFD decrease in contraction to ET-1 in 6J IPA is noted.
Fig. 5: A 12-week HFD does not induce endothelial dysfunction.
Fig. 6: Endothelial-independent smooth muscle relaxation is not affected by HFD.
Fig. 7: HFD does not impair penile nerve-mediated relaxation.


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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,, Grant DK076169 and DK115255.

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Correspondence to Johanna L. Hannan.

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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).

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