Caprylic Acid Restores Branched-Chain Amino Acid Metabolism in a Mouse Cachexia Model

Area of Science:

• Oncology
• Metabolism
• Muscle Biology

Background:

• Cancer-associated sarcopenia significantly impacts patient prognosis and treatment.
• Branched-chain amino acids (BCAAs) are known to support muscle growth but their role in cancer-related muscle loss is unclear.

Purpose of the Study:

• To investigate the efficacy of BCAAs in managing cancer-associated sarcopenia.
• To elucidate the mechanisms underlying BCAA ineffectiveness in cancer patients.

Main Methods:

• Utilized mouse and in vitro cachexia models.
• Administered BCAAs and caprylic acid.
• Assessed oxidative stress, mitochondrial function, cytokine production, and muscle characteristics.
• Analyzed BCAA catabolism pathway, including BCKD kinase and high-mobility group box-1 (HMGB1).

Main Results:

• BCAAs did not improve muscle mass, oxidative stress, or inflammation in cancer models.
• 5-fluorouracil worsened sarcopenia, unaffected by BCAA supplementation.
• Impaired BCAA catabolism, driven by HMGB1-induced BCKD kinase activity, was identified as the cause of ineffectiveness.
• Caprylic acid restored BCAA metabolism and efficacy.

Conclusions:

• BCAA supplementation is ineffective for cancer-associated sarcopenia due to metabolic dysfunction.
• Targeting BCAA metabolism, potentially with agents like caprylic acid, could enhance therapeutic strategies for sarcopenia in cancer patients.