Final Report Summary - LIPOCHEX (The Role of Lipolysis in the Pathogenesis of Cancer-associated Cachexia) LipoCheX investigated the role of triglyceride (TG) catabolism (lipolysis) in the pathogenesis of cancer and cancer-associated cachexia (CAC). Our research revealed novel mechanisms of how lipolysis affects cancer and CAC in mice. We discovered a metabolic axis where CAC induces lipolysis and browning of white adipose tissue contributing to increased energy consumption and wasting. We also identified a new metabolic strategy in adipose tissue to counteract hyper-catabolism and lipotoxicity. The investigation of new animal model of CAC that we established in our laboratory revealed causative factors and pathways for the initiation of CAC. In search of potential treatment strategies, we developed pharmacological inhibitors of lipolysis and found that Atglistatin, an inhibitor of the rate-limiting enzyme of TG degradation in adipose tissue, prevents high-fat diet induced obesity, insulin resistance, hepatosteatosis, and heart failure in mice. Inhibition of lipolysis may represent a promising strategy to treat metabolic diseases in humans.
