Why does carnitine deficiency cause fat to accumulate in muscle fibres?

Carnitine deficiency leads to the accumulation of fat in muscle fibers because it disrupts the essential transport mechanism required for fatty acid metabolism.

In healthy muscle cells, fatty acids must be oxidized within the mitochondria to produce energy. However, fatty acids activated in the cytoplasm cannot cross the mitochondrial membranes on their own. Carnitine acts as a critical carrier molecule in this process: it attaches to fatty acyl groups in the presence of the enzyme carnitine acyl transferase to form acylcarnitine. This compound is then able to cross the mitochondrial membranes, where the fatty acid is released and subsequently oxidized.12

When carnitine is deficient, this shuttle system fails. Consequently, fatty acids cannot reach the site of oxidation and instead remain in the cytoplasm, where they are deposited as droplets of fat (triglycerides). This condition is a hallmark of lipid storage myopathies, where the inability to process fats leads to their abnormal accumulation within the muscle fiber.1