Abstract
Metabolic sex differences have recently been shown to be particularly important in tailoring treatment strategies. Sex has a major effect on fat turnover rates and plasma lipid delivery in the body. Differences in kidney structure and transporters between male and female animals have been found. Here we investigated sex-specific renal pyruvate metabolic flux and whole-kidney functional status in age-matched healthy Wistar rats. Blood oxygenation level–dependent and dynamic contrast-enhanced (DCE) magnetic resonance imaging (MRI) were used to assess functional status. Hyperpolarized [1-13C]pyruvate was used to assess the metabolic differences between male and female rats. Female rats had a 41% ± 3% and 41% ± 5% lower absolute body and kidney weight, respectively, than age-matched male rats. No difference was seen between age-matched male and female rats in the kidney-to-body weight ratio. A 56% ± 11% lower lactate production per mL/100 mL/min was found in female rats than in age-matched male rats measured by hyperpolarized magnetic resonance and DCE MRI. Female rats had a 33% ± 11% higher glomerular filtration rate than age-matched male rats measured by DCE MRI. A similar renal oxygen tension (T2*) was found between age-matched male and female rats as shown by blood oxygenation level–dependent MRI. The results were largely independent of the pyruvate volume and the difference in body weight. This study shows an existing metabolic difference between kidneys in age-matched male and female rats, which indicates that sex differences need to be considered when performing animal experiments.
Highlights
Metabolic sex differences are gaining increasing attention as an important factor in tailoring treatment strategies
This is supported by the higher body weight and kidney weight levels found in the male group than in the female group, while the kidney-weight to body-weight ratio shows no significant difference between the groups
Correction for the metabolic conversion by kidney weight reduced the metabolic differences, which indicates that the number of nephrons could be the origin of this sex difference
Summary
Metabolic sex differences are gaining increasing attention as an important factor in tailoring treatment strategies. Men are at an increased risk of developing nondiabetic renal disease compared to age-matched women [1]. Recent reports have shown sex-specific myocardial metabolic patterns, suggesting differences in treatment effects among male and female individuals. Divergent responses to metformin in myocardial fatty acid (FA) metabolism between women and men appear to explain the lack of treatment effects when treatment groups were analyzed as a whole [4, 5]. It is likely, that similar renal metabolic and functional differences exist between men and women. The differences of renal transporters and renal ammonia metabolism have been reported in rodents with fundamental structural difference between males
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