From the Guidelines
The loss of function mutation of Very long-chain acyl-CoA dehydrogenase (VLCAD) results in increased fatty acid oxidation. VLCAD is a key enzyme in the fatty acid oxidation pathway, responsible for the initial step of breaking down very long-chain fatty acids in the mitochondria 1. When VLCAD function is reduced or lost through mutation, the body compensates by increasing the breakdown of existing fatty acids for energy production, leading to enhanced fatty acid oxidation. This metabolic shift can affect energy homeostasis and may have implications for conditions like obesity and diabetes, as increased fatty acid oxidation can lead to reduced fat storage and improved insulin sensitivity.
Key points to consider:
- VLCAD deficiency is a fatty acid oxidation disorder that can be diagnosed through acylcarnitine profile analysis and mutation analysis 1.
- The disorder is characterized by elevated levels of C14 and C14:1 acylcarnitines in newborn screening 1.
- Diagnostic confirmation requires mutation analysis, and differential diagnosis should include other fatty acid oxidation disorders such as carnitine palmitoyltransferase type II deficiency (CPT II) and multiple acyl-CoA dehydrogenase deficiency (MADD) 1.
- The loss of function mutation of VLCAD can lead to increased fatty acid oxidation, which can have significant implications for energy homeostasis and overall health.
From the Research
Enzyme Involved in Fatty Acid Oxidation
- The loss of function mutation of Acetyl-CoA carboxylase (ACC) results in increased fatty acid oxidation 2, 3, 4.
Role of ACC in Fatty Acid Metabolism
- ACC is an essential rate-limiting enzyme in fatty acid metabolism, playing a key regulatory role in both fatty acid synthesis and oxidation pathways 2, 3.
- ACC catalyzes the carboxylation of acetyl-CoA to produce malonyl-CoA, which inhibits the activity of carnitine palmitoyltransferase 1 (CPT1) and thereby regulates fatty acid oxidation 3, 5.
Effect of ACC Inhibition on Fatty Acid Oxidation
- Inhibition of ACC enzymes, ACC1 and ACC2, offers an attractive therapeutic strategy for nonalcoholic fatty liver disease (NAFLD) through simultaneous inhibition of fatty acid synthesis and stimulation of fatty acid oxidation 4.
- ACC inhibition has been shown to increase hepatic ketogenesis and enhance fatty acid oxidation in rodent models of NAFLD 4.