Importantly, using both mouse models of cancer cachexia and data from healthy individuals and people with cancer, we identified a conserved pathogenetic role for IL-6-induced hepatic expression of Pck1 and Pdk3. Altogether, our findings could pave the way to a potential therapeutic strategy of targeting hepatic gluconeogenesis and PDK3 in IL-6-related cancer cachexia. Here, IL6 is linked to cancer.