Tumor‐secreted proliferin‐1 regulates adipogenesis and lipolysis in cachexia

Abstract Cancer‐associated cachexia (CAC) is a common syndrome in cancer patients and is characterized by loss of body weight accompanied by the atrophy of fat and skeletal muscle. Metabolic changes are a critical factor in CAC; however, the mechanisms through which tumors inhibit adipogenesis and promote lipolysis are poorly understood. To clarify these mechanisms, we investigated adipogenesis‐limiting factors released by tumors in a cell culture system. We identified proliferin‐1 (PLF‐1), a member of the growth hormone/prolactin gene family, as a key factor secreted from certain tumors that inhibited preadipocyte maturation and promoted the lipolysis of mature adipocytes. Importantly, mice transplanted with PLF‐1‐depleted tumor cells were protected from fat loss due to CAC. These data show that tumor‐secreted PLF‐1 plays an essential role in impaired adipogenesis and accelerated lipolysis and is a potential therapeutic target against CAC.