BACKGROUND 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. RESULTS 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. CONCLUSIONS Taken together, my results indicate that CTRP3 has novel roles in regulating both gluconeogenesis and amino acid metabolism in the liver during starvation.