CHRONIC HIGH FAT DIET IMPAIRS DETRUSOR MITOCHONDRIAL FATTY ACID OXIDATION IN MALE BUT NOT FEMALE MICE

INTRODUCTION AND OBJECTIVES:Obesity increases the prevalence of bladder dysfunction in both males and females. The bladder’s mucosal and detrusor smooth muscle layers are involved in bladder signaling and contraction, respectively. The underlying causes of obesity-induced bladder dysfunction in males and females are poorly understood. Mitochondrial dysfunction is common in the heart, liver and skeletal muscle with high fat diet. This study aims to determine the impact of long-term high fat diet (HFD) on bladder mucosal and detrusor mitochondrial respiration in male and female mice.METHODS:Adult male and female mice were fed a control (10% kcal fat) or HFD (45% kcal fat; n=7/group) for 24 weeks. Bladders were collected, weighed and separated into mucosal and detrusor layers. Tissues were cut into strips, permeabilized, and placed in an OROBOROS Oxygraphy-2K to measure respiration. Substrates (pyruvate/malate, glutamate, L-octanoylcarnitine/malate, or succinate/rotenone) were added with increasing concentra...