Alterations in fatty acid metabolism play a causal role in muscle wasting during cancer cachexia

Cancer cachexia is a severe multifactorial syndrome occurring in the 80% of advanced cancer patients and responsible for the 20% of total deaths. Many organs are severally compromised during cachexia, nevertheless the most detrimental alteration occurs in skeletal muscles, that become atrophic. Indeed, muscle atrophy is one of the main clinical features of cachexia and the major responsible for poor treatment tolerance and bed prognosis of cancer patients. Therefore, the identification of all players involved in muscle wasting onset is highly required. Recent publications have highlighted positive correlations, during cancer cachexia, between lipolysis, fatty acid plasma levels and severity of muscle atrophy. The complete protection from cachexia observed in lipase-deficient mouse models together with the reversion of muscle atrophy obtained by treatment with inhibitors of β-oxidation demonstrate that alterations in fatty acid metabolism play a causal role in the onset of muscle atrophy during cancer cachexia. These data indicate the key relevance of metabolism in cancer cachexia and how the deepening of our knowledge in the molecular drivers of atrophy could lead to new and more efficient therapeutic treatments.