ALTERAZIONI DEL FEGATO NELLA CACHESSIA DEL CANCRO SPERIMENTALE: IMPATTO DELLA SOMMINISTRAZIONE DI NIACINA

Cachexia is a complex syndrome characterized by muscle wasting with or without fat loss, which often affects individuals who are in the late stages of an underlying disease, such as cancer and several other chronic illnesses. In addition to the involvement of skeletal muscle, other tissues/organs such as the liver, gastrointestinal tract, adipose tissue, brain and heart are engaged directly in the cachectic process. The liver is highly associated with the cancer cachexia process, from body glucose regulation to the secretion of acute-phase proteins, which is in part a response to pro-inflammatory cytokines. The goal of this experiment is to examine the effect of niacin supplementation on cancer cachexia and the protein expression of metabolic genes in the liver of cancer cachexia mice models while they are under chemotherapy treatment. Female BALB/C mice were injected subcutaneously at 3 months of age with colon-26 (C26) adenocarcinoma cells. Chemotherapy was delivered every 7 days, starting from the day of tumour inoculation. Niacin administration began four days after tumour inoculation and was maintained daily by gavage. We show that the liver of the niacin supplemented C26 bearer BALB/c mice undergoing chemotherapy (FOLFOX) showed a significant enhancement in blood glucose content, skeletal muscle mass, and total body weight. Moreover, several liver metabolic proteins and cofactors are improved upon niacin administration, such as BNIP1, p-AMPK, GAPDH, NAD+ cofactors, and overall protein synthesis rate reduction. This finding supports the increasing importance of liver metabolism in regulating systemic energy homeostasis, and niacin's potential for prospective anti-cachexia treatments in humans.