Acat1-KO Mouse

Acat1, also known as Acyl-coenzyme A:cholesterol acyltransferase 1 or Sterol O-acyltransferase 1 (ACAT1/SOAT1), is a key enzyme in lipid metabolism. It converts free cholesterol to cholesteryl esters, maintaining cholesterol homeostasis, which is crucial for cell membrane integrity, signaling transduction, and normal cell function [2,3,4,5]. It is also involved in fatty acid oxidation and ketogenesis [7]. Genetic models, such as gene knockout (KO) or conditional knockout (CKO) mouse models, have been instrumental in studying its functions.

In KO mouse models, knocking out Acat1 reduced fat mass in mice and inhibited the early stage of adipogenesis via attenuating the PPARγ pathway, suggesting its importance in adipocyte expandability [2]. In cancer research, shRNA-mediated Acat1 ablation repressed lipid metabolism and tumor progression in xenograft and DEN/CCl4-induced hepatocellular carcinoma (HCC), indicating its role in hepatocarcinogenesis [1]. In glioblastoma, myeloid-specific depletion of Acat1 in mice led to increased accumulation of myeloid-derived suppressor cells and enhanced tumor progression [7]. In bladder cancer, knockdown of Acat1 in vitro and in vivo suppressed cell proliferation and migration [6].

In conclusion, Acat1 plays essential roles in lipid metabolism, adipogenesis, and tumor development. Studies using KO/CKO mouse models have revealed its significance in diseases such as obesity-related adipose tissue disorders, HCC, glioblastoma, and bladder cancer, providing valuable insights into potential therapeutic strategies targeting Acat1 for these disease areas.

References:

1. Gu, Li, Zhu, Yahui, Lin, Xi, Lu, Bingjun, Li, Youjun. 2020. Stabilization of FASN by ACAT1-mediated GNPAT acetylation promotes lipid metabolism and hepatocarcinogenesis. In Oncogene, 39, 2437-2449. doi:10.1038/s41388-020-1156-0. https://pubmed.ncbi.nlm.nih.gov/31974474/

2. Liu, Qing, Wu, Xiaolin, Duan, Wei, Zhou, Zhangsen, Zhu, Yuyan. 2024. ACAT1/SOAT1 maintains adipogenic ability in preadipocytes by regulating cholesterol homeostasis. In Journal of lipid research, 65, 100680. doi:10.1016/j.jlr.2024.100680. https://pubmed.ncbi.nlm.nih.gov/39481851/

3. Alavez-Rubio, Jessica Sarahi, Juarez-Cedillo, Teresa. . ACAT1 as a Therapeutic Target and its Genetic Relationship with Alzheimer's Disease. In Current Alzheimer research, 16, 699-709. doi:10.2174/1567205016666190823125245. https://pubmed.ncbi.nlm.nih.gov/31441726/

4. Sun, Tie, Xiao, Xuan. 2024. Targeting ACAT1 in cancer: from threat to treatment. In Frontiers in oncology, 14, 1395192. doi:10.3389/fonc.2024.1395192. https://pubmed.ncbi.nlm.nih.gov/38720812/

5. Shibuya, Yohei, Chang, Catherine Cy, Chang, Ta-Yuan. 2015. ACAT1/SOAT1 as a therapeutic target for Alzheimer's disease. In Future medicinal chemistry, 7, 2451-67. doi:10.4155/fmc.15.161. https://pubmed.ncbi.nlm.nih.gov/26669800/

6. Wang, Tingjun, Wang, Gang, Shan, Danni, Xiao, Yu, Wang, Xinghuan. 2024. ACAT1 promotes proliferation and metastasis of bladder cancer via AKT/GSK3β/c-Myc signaling pathway. In Journal of Cancer, 15, 3297-3312. doi:10.7150/jca.95549. https://pubmed.ncbi.nlm.nih.gov/38817856/

7. Wang, Mingjin, Wang, Weida, You, Shen, Chen, Xiaoguang, Jin, Jing. 2023. ACAT1 deficiency in myeloid cells promotes glioblastoma progression by enhancing the accumulation of myeloid-derived suppressor cells. In Acta pharmaceutica Sinica. B, 13, 4733-4747. doi:10.1016/j.apsb.2023.09.005. https://pubmed.ncbi.nlm.nih.gov/38045043/