ABSTRACT: The liver plays a central role in vertebrate glucose homeostasis, and is also one of the most sexually dimorphic organs in terms of gene expression. While the extent of hepatic sexual dimorphism has been well described in mammals, little is known regarding this phenomenon in non-mammalian species, particularly fish. In this study, we examined hepatic gene expression and physiological phenotypes (growth, proximate body composition, retention efficiencies) to determine whether male and female zebrafish respond differently to diets comprised of 0, 15, 25, or 35 % carbohydrate. Using both Affymetrix microarrays and qRTPCR, we observed substantial sexual dimorphism in the hepatic transcriptome, and the response of some genes to dietary carbohydrate manipulation also varied by sex. Males upregulated genes associated with oxidative metabolism, carbohydrate metabolism, energy production, and amelioration of oxidative stress, while females had higher expression levels of genes associated with translation. Males also expressed elevated levels of hnf4α, a gene thought to be involved in regulating hepatic sexual dimorphism in the rodent. Dietary carbohydrate affected hepatic gene expression, growth performance, retention efficiencies of protein and energy, and percentage of moisture, lipid, and ash. Significant diet effects reflected differences between the 0% carbohydrate diet and the other diets, consistent with previous work on other cyprinids showing a high tolerance for dietary carbohydrate. Our data support the use of the zebrafish as a model for the study of both normal and disease states associated with carbohydrate metabolism, and highlight the importance of accounting for both sex and diet; The liver plays a central role in vertebrate glucose homeostasis, and is also one of the most sexually dimorphic organs in terms of gene expression. While the extent of hepatic sexual dimorphism has been well described in mammals, little is known regarding this phenomenon in non-mammalian species, particularly fish. In this study, we examined hepatic gene expression and physiological phenotypes (growth, proximate body composition, retention efficiencies) to determine whether male and female zebrafish respond differently to diets comprised of 0, 15, 25, or 35 % carbohydrate. Using both Affymetrix microarrays and qRTPCR, we observed substantial sexual dimorphism in the hepatic transcriptome, and the response of some genes to dietary carbohydrate manipulation also varied by sex. Males upregulated genes associated with oxidative metabolism, carbohydrate metabolism, energy production, and amelioration of oxidative stress, while females had higher expression levels of genes associated with translation. Males also expressed elevated levels of hnf4α, a gene thought to be involved in regulating hepatic sexual dimorphism in the rodent. Dietary carbohydrate affected hepatic gene expression, growth performance, retention efficiencies of protein and energy, and percentage of moisture, lipid, and ash. Significant diet effects reflected differences between the 0% carbohydrate diet and the other diets, consistent with previous work on other cyprinids showing a high tolerance for dietary carbohydrate. Our data support the use of the zebrafish as a model for the study of both normal and disease states associated with carbohydrate metabolism, and highlight the importance of accounting for both sex and diet Experiment Overall Design: 17 samples are analyzed from a factorial combination of sex (male or female) and dietary treatment (0% or 25% dietary carbohydrate). 5 biological replicates for females fed each diet, and 3 or 4 biological replicates for males fed the 0% and 25% diets, respectively.
