Department of Molecular Medicine and Surgery, Karolinska Institutet, Sweden.
BMC Biochem. 2010 Sep 23;11:38. doi: 10.1186/1471-2091-11-38.
Genes involved in hepatic metabolism have a sex-different expression in rodents. To test whether male and female rat livers differ regarding lipid and carbohydrate metabolism, whole-genome transcript profiles were generated and these were complemented by measurements of hepatic lipid and glycogen content, fatty acid (FA) oxidation rates and hepatic glucose output (HGO). The latter was determined in perfusates from in situ perfusion of male and female rat livers. These perfusates were also analysed using nuclear magnetic resonance (NMR) spectroscopy to identify putative sex-differences in other liver-derived metabolites. Effects of insulin were monitored by analysis of Akt-phosphorylation, gene expression and HGO after s.c. insulin injections.
Out of approximately 3 500 gene products being detected in liver, 11% were significantly higher in females, and 11% were higher in males. Many transcripts for the production of triglycerides (TG), cholesterol and VLDL particles were female-predominant, whereas genes for FA oxidation, gluconeogenesis and glycogen synthesis were male-predominant. Sex-differences in mRNA levels related to metabolism were more pronounced during mild starvation (12 h fasting), as compared to the postabsorptive state (4 h fasting). No sex-differences were observed regarding hepatic TG content, FA oxidation rates or blood levels of ketone bodies or glucose. However, males had higher hepatic glycogen content and higher HGO, as well as higher ratios of insulin to glucagon levels. Based on NMR spectroscopy, liver-derived lactate was also higher in males. HGO was inhibited by insulin in parallel with increased phosphorylation of Akt, without any sex-differences in insulin sensitivity. However, the degree of Thr172-phosphorylated AMP kinase (AMPK) was higher in females, indicating a higher degree of AMPK-dependent actions.
Taken together, males had higher ratios of insulin to glucagon levels, higher levels of glycogen, lower degree of AMPK phosphorylation, higher expression of gluconeogenic genes and higher hepatic glucose output. Possibly these sex-differences reflect a higher ability for the healthy male rat liver to respond to increased energy demands.
在啮齿类动物中，参与肝脏代谢的基因表现出性别差异。为了测试雄性和雌性大鼠肝脏在脂质和碳水化合物代谢方面是否存在差异，我们生成了全基因组转录谱，并补充了肝脂质和糖原含量、脂肪酸（FA）氧化率和肝葡萄糖输出（HGO）的测量结果。后者是通过原位灌注雄性和雌性大鼠肝脏的灌流液来确定的。这些灌流液也使用核磁共振（NMR）光谱进行了分析，以鉴定其他可能存在的性别差异肝脏来源的代谢物。通过分析皮下注射胰岛素后的 Akt 磷酸化、基因表达和 HGO 来监测胰岛素的作用。
在肝脏中检测到的大约 3500 种基因产物中，有 11%的基因在雌性中显著升高，有 11%的基因在雄性中升高。许多与甘油三酯（TG）、胆固醇和 VLDL 颗粒生成相关的转录本在雌性中占优势，而与 FA 氧化、糖异生和糖原合成相关的基因在雄性中占优势。与代谢相关的 mRNA 水平的性别差异在轻度饥饿（12 小时禁食）时比在吸收后状态（4 小时禁食）更为明显。在肝 TG 含量、FA 氧化率或酮体和葡萄糖的血液水平方面，没有观察到性别差异。然而，雄性的肝糖原含量较高，HGO 较高，胰岛素与胰高血糖素的比值也较高。基于 NMR 光谱，肝脏来源的乳酸在雄性中也较高。HGO 被胰岛素抑制，同时 Akt 的磷酸化增加，胰岛素敏感性没有性别差异。然而，雌性的 Thr172 磷酸化 AMP 激酶（AMPK）程度较高，表明 AMPK 依赖性作用的程度较高。
综上所述，雄性的胰岛素与胰高血糖素比值较高，糖原水平较高，AMPK 磷酸化程度较低，糖异生基因表达较高，肝葡萄糖输出较高。这些性别差异可能反映了健康雄性大鼠肝脏对增加能量需求的更高适应能力。
