Acsbg1, also known as "bubblegum" acyl-CoA synthetase, is a key player in lipid metabolism. It facilitates the activation of long-chain fatty acids (LCFAs) and their integration into essential lipid species, supporting processes like membrane formation, myelination, and energy production [3,4]. It is involved in pathways related to fatty acid metabolism and has significance in maintaining lipid homeostasis in various tissues, especially the brain [3,4]. Genetic models, such as knockout mouse models, have been crucial in studying its functions.

In gene knockout studies, Acsbg1-deficient Treg cells showed mitochondrial dysfunction and dampened other metabolic pathways, indicating its role as a metabolic checkpoint for tissue Treg cell homeostasis and resolution of lung inflammation [1]. In CD4+ T cells, Acsbg1 deficiency led to impaired TH17 and iTreg differentiation, highlighting its importance in maintaining immune homeostasis by regulating T cell differentiation [2]. In the context of X-linked adrenoleukodystrophy (XALD), although Acsbg1 knockout mice did not show typical XALD-related changes in total ACS enzyme activity, there were notable developmental and compositional changes in fatty acid levels in the brain, suggesting its role in brain lipid metabolism [3,4]. In diabetic cardiomyopathy, Acsbg1 was identified as a hub gene associated with fatty acid metabolism, potentially affecting the disease's occurrence and progression through the lysosome [5].

In summary, Acsbg1 is essential for lipid metabolism, especially in the activation of LCFAs. Model-based research, particularly using Acsbg1 knockout mouse models, has revealed its roles in immune cell homeostasis, brain lipid metabolism, and potentially in diseases like XALD and diabetic cardiomyopathy. These findings contribute to understanding the underlying mechanisms of these biological processes and diseases, providing insights for potential therapeutic strategies.

References:

1. Kanno, Toshio, Nakajima, Takahiro, Kawashima, Yusuke, Nakayama, Toshinori, Endo, Yusuke. . Acsbg1-dependent mitochondrial fitness is a metabolic checkpoint for tissue Treg cell homeostasis. In Cell reports, 37, 109921. doi:10.1016/j.celrep.2021.109921. https://pubmed.ncbi.nlm.nih.gov/34758300/

2. Palatella, Martina, Kruse, Friederike, Glage, Silke, Greweling-Pils, Marina, Huehn, Jochen. 2025. Acsbg1 regulates differentiation and inflammatory properties of CD4+ T cells. In European journal of microbiology & immunology, 15, 21-31. doi:10.1556/1886.2025.00003. https://pubmed.ncbi.nlm.nih.gov/39937199/

3. Ye, Xiaoli, Li, Yuanyuan, González-Lamuño, Domingo, Smith, Kirby D, Watkins, Paul A. 2024. Role of ACSBG1 in brain lipid metabolism and X-linked adrenoleukodystrophy pathogenesis: Insights from a knockout mouse model. In bioRxiv : the preprint server for biology, , . doi:10.1101/2024.06.19.599741. https://pubmed.ncbi.nlm.nih.gov/38948805/

4. Ye, Xiaoli, Li, Yuanyuan, González-Lamuño, Domingo, Smith, Kirby D, Watkins, Paul A. 2024. Role of ACSBG1 in Brain Lipid Metabolism and X-Linked Adrenoleukodystrophy Pathogenesis: Insights from a Knockout Mouse Model. In Cells, 13, . doi:10.3390/cells13201687. https://pubmed.ncbi.nlm.nih.gov/39451204/

5. Huang, Xun, Wang, Yunhong, Wan, Rong, You, Zhigang, Huang, Lin. 2025. Identification of lipid metabolism-related genes in dapagliflozin treated rats with diabetic cardiomyopathy by bioinformatics. In Frontiers in endocrinology, 16, 1525831. doi:10.3389/fendo.2025.1525831. https://pubmed.ncbi.nlm.nih.gov/40182633/