Carnitine palmitoyltransferase 1A (CPT1A) (CPT1A)

Carnitine palmitoyltransferase 1A (CPT1A) is a critical regulatory enzyme located on the outer mitochondrial membrane that facilitates the rate-limiting step of long-chain fatty acid transport into the mitochondria for beta-oxidation (UniProt P50416). It functions by converting long-chain acyl-CoAs into acylcarnitines, allowing them to pass through the mitochondrial membranes to be utilized for energy production and ketogenesis (PubMed: 28864413). CPT1A is primarily expressed in the liver and plays a vital role in maintaining energy homeostasis during fasting or metabolic stress. In diseases like type 2 diabetes and non-alcoholic fatty liver disease (NAFLD), CPT1A activity is often suppressed, contributing to lipid accumulation and metabolic dysfunction. Empagliflozin, while primarily an SGLT2 inhibitor, has been shown to indirectly enhance CPT1A expression and activity, promoting a metabolic shift from glucose to fatty acid oxidation and the production of ketone bodies (PubMed: 31108133). This shift is considered a significant component of the drug's cardioprotective and renoprotective profile, as it provides the heart and kidneys with a more oxygen-efficient fuel source (NIH: PMC6682519).

Other names

CPT1-LCarnitine O-palmitoyltransferase 1, liver isoformCPT1L-CPT1

Empagliflozin indirectly upregulates CPT1A expression and activity by altering the insulin-to-glucagon ratio and activating AMPK pathways, which reduces malonyl-CoA inhibition and promotes fatty acid entry into the mitochondria for oxidation.