Abcg1-KO Mouse

Abcg1, an ATP-binding cassette half transporter, is crucial in facilitating the efflux of excess cholesterol from macrophages [3]. It is involved in the reverse cholesterol transport (RCT) pathway, where it contributes to the elimination of excessive cholesterol from the body. Specifically, ABCG1 facilitates the continued cholesterol efflux to high-density lipoprotein (HDL) for its further maturation, maintaining cellular cholesterol homeostasis [2]. ABCG1 is induced by the LXR/RXR pathway and is regulated transcriptionally, post-transcriptionally, and post-translationally [1].

In a study of mice genetically lacking Abcg1 in the myeloid lineage, an ameliorated inflammatory status in adipose tissue and reduced insulin resistance were observed. Abcg1-deficient adipose tissue macrophages (ATMs) showed a less inflammatory phenotype with a low bioenergetic profile and modified fatty acid (FA) metabolism. The lipidome analysis revealed a shift in FA pools, reducing membrane rigidity and neutralizing pro-inflammatory FAs. This indicates that Abcg1 plays a role in orchestrating ATM plasticity and insulin resistance in diet-induced obesity (DIO) [4].

In conclusion, Abcg1 is essential for maintaining cholesterol homeostasis, especially in macrophages. The study of Abcg1-deficient mouse models has revealed its role in regulating inflammation and insulin resistance in obesity-related conditions. Understanding the function of Abcg1 provides insights into potential therapeutic strategies for diseases such as atherosclerosis and metabolic disorders associated with abnormal lipid metabolism [1,3,4].

References:

1. Matsuo, Michinori. 2021. ABCA1 and ABCG1 as potential therapeutic targets for the prevention of atherosclerosis. In Journal of pharmacological sciences, 148, 197-203. doi:10.1016/j.jphs.2021.11.005. https://pubmed.ncbi.nlm.nih.gov/35063134/

2. Yu, Xiao-Hua, Tang, Chao-Ke. . ABCA1, ABCG1, and Cholesterol Homeostasis. In Advances in experimental medicine and biology, 1377, 95-107. doi:10.1007/978-981-19-1592-5_7. https://pubmed.ncbi.nlm.nih.gov/35575923/

3. Ito, Toshimitsu. . Physiological function of ABCG1. In Drug news & perspectives, 16, 490-2. doi:. https://pubmed.ncbi.nlm.nih.gov/14668945/

4. Dahik, Veronica D, Kc, Pukar, Materne, Clément, Venteclef, Nicolas, Le Goff, Wilfried. 2024. ABCG1 orchestrates adipose tissue macrophage plasticity and insulin resistance in obesity by rewiring saturated fatty acid pools. In Science translational medicine, 16, eadi6682. doi:10.1126/scitranslmed.adi6682. https://pubmed.ncbi.nlm.nih.gov/39661702/