Acot2, or acyl-CoA thioesterase 2, hydrolyzes acyl-coenzyme A (CoA) into free fatty acids and CoA, thus playing a significant role in lipid metabolism pathways, such as fatty acid elongation and biosynthesis of unsaturated fatty acids [1,2,3,4,5,6,7,8]. It is expressed in highly oxidative tissues, including liver and skeletal muscle, and may contribute to maintaining the balance of free fatty acids and acyl CoA at the cellular level [2,3,4,6]. Genetic models could potentially be used to further study its functions.

In acute myeloid leukemia (AML), high expression of ACOT2 is associated with poor overall survival and abnormal lipid metabolism, making it a potential therapeutic target [1]. In Chinese Red Steppe cattle, overexpression of Acot2 promotes preadipocyte differentiation and lipid droplet accumulation, while its down-regulation inhibits these processes, suggesting it is a positive regulator of adipocyte differentiation [2]. In mice, adenoviral Acot2 overexpression in the liver increases fatty acid oxidation during the daytime, leading to higher serum ketones and less hepatic steatosis during overnight fasting [3]. In murine skeletal muscle, Acot2 deletion results in acyl-CoA build-up under certain conditions and affects the preference for glucose or fatty acid oxidation, as well as glucose homeostasis in high-fat-fed mice [4].

In conclusion, Acot2 is crucial for lipid metabolism, influencing processes like adipocyte differentiation, fatty acid oxidation, and glucose homeostasis. The use of genetic models, such as overexpression or deletion in mouse models, has provided insights into its role in diseases like AML and metabolic conditions related to lipid metabolism [1,2,3,4].

References:

1. Yin, Xuewei, Lyu, Chunyi, Li, Zonghong, Guo, Dadong, Xu, Ruirong. 2022. High Expression of ACOT2 Predicts Worse Overall Survival and Abnormal Lipid Metabolism: A Potential Target for Acute Myeloid Leukemia. In Journal of healthcare engineering, 2022, 2669114. doi:10.1155/2022/2669114. https://pubmed.ncbi.nlm.nih.gov/36193167/

2. Liu, Lixiang, Wu, Jian, Gao, Yi, Cao, Yang, Zhang, Guoliang. . The effect of Acot2 overexpression or downregulation on the preadipocyte differentiation in Chinese Red Steppe cattle. In Adipocyte, 9, 279-289. doi:10.1080/21623945.2020.1776553. https://pubmed.ncbi.nlm.nih.gov/32579860/

3. Moffat, Cynthia, Bhatia, Lavesh, Nguyen, Teresa, Claypool, Steven M, Seifert, Erin L. 2014. Acyl-CoA thioesterase-2 facilitates mitochondrial fatty acid oxidation in the liver. In Journal of lipid research, 55, 2458-70. doi:10.1194/jlr.M046961. https://pubmed.ncbi.nlm.nih.gov/25114170/

4. Bekeova, Carmen, Han, Ji In, Xu, Heli, Snyder, Nathaniel W, Seifert, Erin L. 2023. Acyl-CoA thioesterase-2 facilitates β-oxidation in glycolytic skeletal muscle in a lipid supply dependent manner. In bioRxiv : the preprint server for biology, , . doi:10.1101/2023.06.27.546724. https://pubmed.ncbi.nlm.nih.gov/37425757/

5. Momose, Atsushi, Fujita, Mariko, Ohtomo, Takayuki, Morikawa, Masako, Yamada, Junji. 2010. Regulated expression of acyl-CoA thioesterases in the differentiation of cultured rat brown adipocytes. In Biochemical and biophysical research communications, 404, 74-8. doi:10.1016/j.bbrc.2010.11.066. https://pubmed.ncbi.nlm.nih.gov/21094633/

6. Bekeova, Carmen, Anderson-Pullinger, Lauren, Boye, Kevin, Herrmann, Johannes M, Seifert, Erin L. 2019. Multiple mitochondrial thioesterases have distinct tissue and substrate specificity and CoA regulation, suggesting unique functional roles. In The Journal of biological chemistry, 294, 19034-19047. doi:10.1074/jbc.RA119.010901. https://pubmed.ncbi.nlm.nih.gov/31676684/

7. Del Duca, Ester, Dahabreh, Dante, Kim, Madeline, Agache, Ioana, Guttman-Yassky, Emma. 2024. Transcriptomic evaluation of skin tape-strips in children with allergic asthma uncovers epidermal barrier dysfunction and asthma-associated biomarkers abnormalities. In Allergy, 79, 1516-1530. doi:10.1111/all.16060. https://pubmed.ncbi.nlm.nih.gov/38375886/

8. Sun, Yuchen, Sun, Bo, Han, Xuesong, Shan, Anshan, Ma, Qingquan. . Leucine Supplementation Ameliorates Early-Life Programming of Obesity in Rats. In Diabetes, 72, 1409-1423. doi:10.2337/db22-0862. https://pubmed.ncbi.nlm.nih.gov/37196349/