Sex differences in bronchoconstriction in diet-induced obese rats

Abstract

Background: Obesity is a major risk factor for asthma; however, the effect of obesity on asthma risk varies by sex. The mechanisms that cause these sex differences are unclear. Aim: To test if obesity affects bronchoconstriction response in male and female adolescent rats. Methods: Six week old obese prone rats (male and female) were fed a high or low fat diet for 5 weeks. Food intake, body weight, body fat composition, and fasting glucose were measured. Bronchoconstriction was measured in vagotomized, fasted, and anesthetized rats in response to 1) electrical stimulation of vagus nerves (2-30Hz) and 2) inhaled methacholine (1-300 mM) to differentiate airway hyperresponsiveness due to changes in nerve function versus M3 muscarinic receptor function on airway smooth muscle, respectively. Results: Male and female non-obese rats (on low fat diet) had similar bronchoconstriction in response to vagal stimulation. In contrast, male obese rats (on high fat diet) had significantly greater bronchoconstriction to vagal stimulation than did female obese rats (on high fat diet). Airway responses to inhaled methacholine were not different between the sexes on high fat diet. While a high fat diet induced obesity in all animals, male rats gained significantly more body weight but had less body fat than female rats. Fasting glucose did not differ between male and female rats, regardless of diet. Conclusions: Diet-induced obesity causes increased vagally-mediated bronchoconstriction in male compared to female adolescent rats. This difference is not explained by diet or changes in M3 muscarinic receptor function on airway smooth muscle. Sex-specific factors may be involved in regulating vagally-mediated bronchoconstriction in obesity.