2nd alternative route of fatty acid oxidation due to carnitine deficiency induced by meldonium is AMPK activation
Reduced mitochondrial FAO flux causes an energy deficit signal within cells, the AMP:ATP ratio rises, which activates AMPK . This is often overlooked. AMPK activation:
- Promotes GLUT4 translocation, increasing glucose uptake and oxidation in muscle, the well-documented glycolytic shift caused by meldonium
- Activates PGC-1α, driving mitochondrial biogenesis and upregulating oxidative capacity over time
- Inhibits lipogenic pathways in adipose tissue: AMPK activation in WAT suppresses de novo lipogenesis and, in some contexts, inhibits insulin-stimulated glucose re-esterification into fat (DNL becomes even more difficult)
- Activates HSL (hormone-sensitive lipase) in adipocytes, promoting lipolysis and mobilization of stored triglycerides
So, UNDER ENERGY DEFICIT, meldonium-driven AMPK activation simultaneously reduces fat synthesis and promotes fat mobilization from adipose stores, even while blunting the mitochondrial route of fat combustion in muscle. So fat becomes harder to be made from sugar, and stored fat is released 'better'
Fat mass loss under energy deficit requires:
- Lipolysis in adipocytes (HSL, ATGL activity): areleasing FFAs into circulation ✅ AMPK-activated by meldonium
- Net energy deficit: caloric expenditure > intake ✅ Unaffected; possibly enhanced via peroxisomal thermogenesis
- Suppression of lipogenesis and re-esterification ✅ AMPK suppresses ACC and lipogenic gene expression
None of these steps require mitochondrial carnitine-dependent FAO in skeletal muscle . The mobilized FFAs can be oxidized through peroxisomal pathways, channeled to other tissues (liver, heart), or used for thermogenesis
Use carnitine or use meldonium, many pharmacometabolic routes to the same goal