From the Research
Fatty acid synthase impairs the conversion of acetyl-CoA to fatty acids, a crucial step in de novo lipogenesis, particularly in tissues with high lipogenic activity such as liver and adipose tissue. This enzyme is a multi-enzyme protein that catalyzes the synthesis of long-chain fatty acids from acetyl-CoA and malonyl-CoA precursors 1. When fatty acid synthase is impaired, either through genetic mutations, pharmacological inhibition, or metabolic dysregulation, the body cannot efficiently convert excess carbohydrates (which are broken down to acetyl-CoA) into fatty acids for energy storage. This disruption affects lipid metabolism broadly, potentially leading to altered membrane composition, reduced energy storage capacity, and changes in cell signaling pathways that depend on lipid intermediates.
The impairment of this metabolic conversion is particularly significant in the context of diseases like obesity, metabolic syndrome, and certain cancers, where excessive fatty acid synthesis contributes to disease progression 2, 3. Recent studies have highlighted the role of de novo lipogenesis in the development of type 2 diabetes, with fatty acids in this pathway being positively associated with the incidence of type 2 diabetes independent of insulin sensitivity 4. Furthermore, dietary factors such as fructose consumption can enhance hepatic de novo lipogenesis, contributing to the development of nonalcoholic fatty liver disease (NAFLD) 5.
Key points to consider include:
- Fatty acid synthase is crucial for the conversion of acetyl-CoA to fatty acids in de novo lipogenesis.
- Impairment of fatty acid synthase affects lipid metabolism and energy storage.
- De novo lipogenesis is significant in tissues like liver and adipose tissue.
- Excessive fatty acid synthesis contributes to diseases like obesity, metabolic syndrome, and certain cancers.
- Dietary factors like fructose can enhance hepatic de novo lipogenesis, contributing to NAFLD.
Given the most recent and highest quality evidence, the impairment of fatty acid synthase activity is most closely associated with the disruption of the conversion of acetyl-CoA to fatty acids, highlighting the importance of this enzyme in lipid metabolism and its potential as a therapeutic target for metabolic diseases 3.