ACOT8
- Known as:
- ACOT8
- Catalog number:
- 001021A
- Product Quantity:
- 250ul
- Category:
- -
- Supplier:
- ABM
- Gene target:
- ACOT8
Related genes to: ACOT8
- Gene:
- ACOT8 NIH gene
- Name:
- acyl-CoA thioesterase 8
- Previous symbol:
- PTE1
- Synonyms:
- hACTE-III, hTE, PTE-2, NAP1
- Chromosome:
- 20q13.12
- Locus Type:
- gene with protein product
- Date approved:
- 2001-08-01
- Date modifiied:
- 2015-10-16
Related products to: ACOT8
Related articles to: ACOT8
- Non-alcoholic fatty liver disease (NAFLD) represents a burgeoning global health burden with limited pharmacological options. Ergothioneine (EGT), a naturally occurring antioxidant, shows potential hepatoprotective effects; however, the exact mechanisms by which EGT regulates lipid metabolism in NAFLD remain elusive. - Source: PubMed
Publication date: 2026/04/25
Ye RongyiWang YihanWang KeboHuang NanLiu GuoGao DexinLi XinruYang MengxueWang JingChen Chen - Renal ischemia-reperfusion injury (IRI) is a major cause of acute kidney injury, involving complex mechanisms of metabolic dysregulation and immune inflammation. This study investigated the role and molecular mechanism of acyl-CoA thioesterase 8 (ACOT8) in IRI by integrating multi-omics data with multi-level experimental validation. A pQTL-based Mendelian randomization analysis identified 456 genes with putative causal associations with AKI. Integrated analysis of multiple transcriptomic datasets, combined with machine learning algorithms (LASSO and SVM-RFE), identified four core candidate genes. Among them, ACOT8 was highly expressed specifically in renal tubular epithelial cells and showed a significant positive correlation with M1 macrophage infiltration. In vivo and in vitro experiments confirmed that ACOT8 was upregulated during IRI. Single-cell RNA sequencing and lipidomics revealed suppressed mitochondrial oxidative metabolism and significant lipid accumulation, particularly palmitate, in injured proximal tubules. Mechanistically, ACOT8 was found to modulate palmitate levels in tubular epithelial cells, thereby altering the local lipid milieu. This palmitate subsequently activated the cGAS-STING signaling pathway in macrophages, promoting their polarization toward a pro-inflammatory M1 phenotype and exacerbating the inflammatory response. Using an AAV9 vector with a kidney-specific promoter to knock down ACOT8 in tubular epithelial cells in a mouse model, we demonstrated that inhibiting ACOT8 significantly attenuated renal palmitate accumulation, reduced M1 macrophage infiltration, lowered serum pro-inflammatory cytokine levels, and improved renal function. In conclusion, this study demonstrates that ACOT8-mediated tubular palmitate accumulation promotes macrophage M1 polarization via the cGAS-STING pathway, thereby contributing to renal ischemia-reperfusion injury. ACOT8 represents a potential therapeutic target for ischemic kidney injury. - Source: PubMed
Publication date: 2026/03/28
Zhang HaoxunLiu XinyuJi XuranZhang GuolingWang BowenXiong FengSun DongmeiWang Chunyang - Primary biliary cholangitis is characterized by breaking of immune tolerance and disorders of bile acid metabolism. Our previous study found that abnormal expression of Lamp2 was detected in PBC patients. However, the specific role of Lamp2a in disease progression is still unclear. In this study, we showed that hepatic-specific Lamp2a deficiency could aggravate the inflammatory phenotype of murine autoimmune cholangitis. Mechanistically, the loss of Lamp2a in hepatocytes contributed to the abnormal accumulation of Acot8, thus altered the bile acid components, thereby enhancing the lymphocyte activities, and ultimately promoting the inflammatory phenotype of model mice. Moreover, we also found that Acot8 knockdown could alleviate the liver inflammation caused by Lamp2a deficiency. Altogether, our findings explored the effect of Lamp2a deficiency on the murine autoimmune cholangitis by the perspective of bile acid metabolism, and marked the possibility of Acot8 as a new target for the treatment of PBC disease. - Source: PubMed
Publication date: 2025/01/16
Fan QinglingGuo GuanyaHu YinanLu YiSu RuiYang JiaqiXia ErzhuoMa ShuoyiZhang MiaoWang JingboLi TingHan Ying - Pancreatic ductal adenocarcinoma (PDAC) comprises a group of highly malignant tumors of the pancreas. Metabolic reprogramming in tumors plays a pivotal role in promoting cancer progression. However, little is known about the metabolic alterations in tumors that drive cancer drug resistance in patients with PDAC. Here, we identified acyl-CoA thioesterase 8 (ACOT8) as a key player in driving PDAC gemcitabine (GEM) resistance. The expression of ACOT8 is significantly upregulated in GEM-resistant PDAC tissues and is closely associated with poor survival in patients with PDAC. Gain- and loss-of-function studies have shown that ACOT8 drives PDAC GEM resistance both in vitro and in vivo. Mechanistically, ACOT8 regulates cellular cholesterol ester (CE) levels, decreases the levels of phosphatidylethanolamines (PEs) that bind to polyunsaturated fatty acids and promote peroxisome activation. The knockdown of ACOT8 promotes ferroptosis and increases the chemosensitivity of tumors to GEM by inducing ferroptosis-associated pathway activation in PDAC cell lines. The combination of orlistat, an ACOT8 inhibitor, and GEM significantly inhibited tumor growth in PDAC organoid and mouse models. This study reveals the biological importance of ACOT8 and provides a potential combination therapy for treating patients with advanced GEM-resistant PDAC. - Source: PubMed
Publication date: 2025/02/12
Li Bo-RuiWang TingHu Hai-FengWu DiZhou Chen-JieJi Shun-RongZhuo Qi-FengLi ZhengWang Zhi-LiangFan Gui-XiongJing De-ShengYu Chong-YuanQin YiChen Xue-MinXu Jun-FengXu Xiao-Wu - Assisted reproduction technologies (ARTs) are generally considered safe; however, emerging evidence highlights the need to evaluate potential risks in adulthood to improve safety further. ART procedures like rederivation of embryos by vitrification differ from natural conditions, causing significant disparities between in vitro and in vivo embryos, affecting foetal physiology and postnatal life. This study aims to investigate whether hepatic transcriptome and metabolome changes observed postnatally are already present in foetal livers at the end of gestation. This study compared fresh and vitrified rabbit embryos, finding differences between foetuses obtained by the transfer of fresh and vitrified embryos at 24 days of gestation. Rederived embryos had reduced foetal and liver weights and crown-rump length. However, the offspring of vitrified embryos tended to be born with higher weight, showing compensatory growth in the final week of gestation (59.2 vs. 49.8 g). RNA-Seq analysis revealed 43 differentially expressed genes (DEGs) in the foetal liver of vitrified embryos compared to the fresh group. Notably, downregulated genes included BRAT1, CYP4A7, CYP2B4, RPL23, RPL22L1, PPILAL1, A1BG, IFGGC1, LRRC57, DIPP2, UGT2B14, IRGM1, NUTF2, MPST, and PPP1R1B, while upregulated genes included ACOT8, ERICH3, UBXN2A, METTL9, ALDH3A2, DERPC-like, NR5A2-like, AP-1, COG8, INHBE, and PLA2G4C. Overall, a functional annotation of these DEGs indicated an involvement in lipid metabolism and the stress and inflammatory process or immune response. Thus, our results suggest that vitrification and embryo transfer manipulation induce an adaptive response that can be observed in the liver during the last week of gestation. - Source: PubMed
Publication date: 2024/08/01
Vicente José SalvadorValdés-Hernández JesúsMarco-Jiménez Francisco