Genetic Variation of Human Long-Chain Fatty Acyl-CoA Synthetase and Nutritional Implication

Interindividual genetic differences influence the metabolism, absorption, and utilization of nutrients in various biological processes. In nutrition research, elucidating gene functions and understanding polymorphisms are essential for clarifying how genetic variations influence individual responses to diet, metabolism, and health outcomes. Long-chain fatty acyl-CoA synthetase (ACSL) catalyzes the conversion of long-chain fatty acids into acyl-CoA forms, which are channeled into multiple metabolic processes. Several isoforms of ACSL have been identified, each with unique metabolic properties. The functional characterization of ACSL has been extensively explored both in vitro and in vivo in recent years. These experimental investigations of gene functions may provide valuable information for human applications. This review summarizes ACSL polymorphisms reported to date and their functional implications. Most studies on human ACSL have employed genome-wide association studies, and each reported ACSL single-nucleotide polymorphism (SNP) has been associated with specialized functions, but the metabolic effects of ACSL SNPs were moderate or, in some traits, remain inconclusive. Yet, the direction of gene expression or function based on each ACSL variant has not been clearly indicated in existing genome-wide association studies' results. Thus, ACSL-based target mechanisms for nutrition intervention could not be specified. Further research should be conducted on studies that employ expression quantitative trait loci datasets, standardized nutrition assessment, and polygenic score approaches.