Department of Anatomy and Cell Biology, Graduate School of Dentistry, Osaka University, 1-8 Yamadaoka, Suita, Osaka, 565-0871, Japan.
Mol Biol Rep. 2022 Feb;49(2):1617-1622. doi: 10.1007/s11033-021-06969-8. Epub 2021 Nov 23.
Adipose tissue secretes various adipocytokines that play important roles in lipid and glucose metabolism. C1q and tumor necrosis factor-related protein 3 (CTRP3) is a paralog of adiponectin, which has been extensively studied. Previously, we showed that epididymal white adipose tissue size is decreased in high fat diet-fed Ctrp3 knockout (KO) mice. Here, I examined metabolic roles of CTRP3 in non-obese mice under starvation conditions.
Serum alanine aminotransferase (ALT) and aspartate aminotransferase (AST) levels were increased in 20-h-fasted standard chow-fed Ctrp3 KO mice compared with wild-type (WT) controls. RT-qPCR analysis revealed that ALT1, AST2, and glucose-6-phosphatase mRNA expressions were increased in the liver of Ctrp3 KO mice after a 20-h fast. Upon intraperitoneal alanine administration, Ctrp3 KO mice showed a modest but significant increase in the conversion of alanine to glucose. To characterize hepatic metabolism in fasted Ctrp3 KO mice, I further analyzed metabolomic profiles in the liver. Unexpectedly, metabolome analysis of the liver of 20-h-fasted Ctrp3 KO mice revealed that the relative concentrations of 10 of the 20 amino acids were lower than in WT controls. The relative concentrations of ornithine and argininosuccinate, which are urea cycle intermediates, were also decreased in the Ctrp3 KO liver.
Taken together, my results indicate that CTRP3 has novel roles in regulating both gluconeogenesis and amino acid metabolism in the liver during starvation.
脂肪组织分泌各种脂肪细胞因子，在脂质和葡萄糖代谢中发挥重要作用。C1q 和肿瘤坏死因子相关蛋白 3（CTRP3）是脂联素的同源物，已被广泛研究。先前，我们表明高脂肪饮食喂养的 Ctrp3 敲除（KO）小鼠附睾白色脂肪组织大小减小。在这里，我研究了 CTRP3 在非肥胖饥饿状态下的非肥胖小鼠中的代谢作用。
与野生型（WT）对照相比，20 小时禁食标准饲料喂养的 Ctrp3 KO 小鼠血清丙氨酸氨基转移酶（ALT）和天冬氨酸氨基转移酶（AST）水平升高。RT-qPCR 分析显示，20 小时禁食后 Ctrp3 KO 小鼠肝脏中 ALT1、AST2 和葡萄糖-6-磷酸酶 mRNA 表达增加。在腹腔内给予丙氨酸后，Ctrp3 KO 小鼠中丙氨酸向葡萄糖的转化略有但显著增加。为了表征禁食 Ctrp3 KO 小鼠的肝脏代谢，我进一步分析了肝脏的代谢组学图谱。出乎意料的是，20 小时禁食 Ctrp3 KO 小鼠肝脏的代谢组学分析显示，10 种 20 种氨基酸中的相对浓度低于 WT 对照。尿素循环中间产物鸟氨酸和精氨酸琥珀酸的相对浓度在 Ctrp3 KO 肝脏中也降低。
综上所述，我的结果表明，CTRP3 在饥饿期间肝脏的糖异生和氨基酸代谢中具有新的作用。
