Objectives: To investigate the effect of high-fat diet (HFD) on bladder M 1,3 muscarinic receptor expression and contractile function in the rat. Methods: Eight-week-old male rats were divided into two groups including one with HFD for 8 weeks (short-term) and the other for 24 weeks (long-term). Each group was compared to age-matched rats fed with normal chow as controls. The body weight, food intake amount and blood biochemistry were monitored. Bladder muscle contractile responses to acetylcholine (0.1–10 μM), bethanechol (10 μM) and KCl (50 mM) were studied in an organ bath set-up. Bladder M 1 and M 3 muscarinic receptor protein expressions were measured by Western blotting analysis. Results: Increase in body weight as well as blood triglyceride, cholesterol and sugar levels compared to controls were noted in both 8- and 24-week HFD rats. Eating appetite change with increased food and water intakes was noted in the HFD rats. Significantly decreased bladder contractile responses to acetylcholine and bethanechol were shown in both HFD groups. On the other hand, decreased bladder contractile response to KCl was demonstrated in the 24-week group but not the 8-week group. The expressions of bladder M 1 and M 3 muscarinic receptor proteins were significantly and progressively decreased by HFD feeding from 8 to 24 weeks. Conclusions: High-fat diet induces obesity and polyphagia in rats. Short-term and long-term HFD feeding decrease rat bladder M 1 and M 3 receptor expressions as well as contractile responses to the agonistic stimulation. In addition, bladder muscle dysfunction develops after long-term HFD feeding.
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