Mlxipl-KO Mouse

Mlxipl, also known as carbohydrate-responsive element-binding protein, is an important regulator of glucolipid metabolism. It plays a crucial role in the transcriptional regulation of lipogenic genes, participating in processes like de novo lipogenesis (DNL), which is significant for energy storage as triglycerides in hepatocytes [3,4,5].

In the context of diseases, in prostate cancer, MLXIPL related to tumor-infiltrating CD8+ T cells is associated with a poor prognosis [1]. In hepatocellular carcinoma, MLXIPL levels are elevated, and it promotes cell migration, invasion, and glycolysis by phosphorylating mTOR [2]. A common missense variant in MLXIPL, Gln241His, is associated with various metabolic phenotypes such as lower serum triglyceride levels, but also a higher risk of steatotic liver disease (SLD), especially in female, obese carriers or those with the PNPLA3 I148M variant [6]. In the spinal dorsal horn after peripheral nerve injury, Mlxipl upregulation induced by cJun counteracts mechanical allodynia by inhibiting neuroinflammation [7].

In summary, Mlxipl is vital for glucolipid metabolism, influencing key processes like DNL. Its dysregulation is implicated in multiple disease conditions including cancer, liver diseases, and neuropathic pain. Understanding Mlxipl through in-vivo studies and gene-based models could potentially provide new therapeutic targets for these diseases.

References:

1. Fan, Yuanming, Ge, Yuqiu, Niu, Kaiming, Zhu, Haixia, Ma, Gaoxiang. 2024. MLXIPL associated with tumor-infiltrating CD8+ T cells is involved in poor prostate cancer prognosis. In Frontiers in immunology, 15, 1364329. doi:10.3389/fimmu.2024.1364329. https://pubmed.ncbi.nlm.nih.gov/38698844/

2. Chang, Xiaowei, Tian, Chang, Jia, Yuanyuan, Cai, Yu, Yan, Pu. 2023. MLXIPL promotes the migration, invasion, and glycolysis of hepatocellular carcinoma cells by phosphorylation of mTOR. In BMC cancer, 23, 176. doi:10.1186/s12885-023-10652-5. https://pubmed.ncbi.nlm.nih.gov/36809979/

3. Wang, Yuhui, Viscarra, Jose, Kim, Sun-Joong, Sul, Hei Sook. . Transcriptional regulation of hepatic lipogenesis. In Nature reviews. Molecular cell biology, 16, 678-89. doi:10.1038/nrm4074. https://pubmed.ncbi.nlm.nih.gov/26490400/

4. Régnier, Marion, Carbinatti, Thaïs, Parlati, Lucia, Benhamed, Fadila, Postic, Catherine. 2023. The role of ChREBP in carbohydrate sensing and NAFLD development. In Nature reviews. Endocrinology, 19, 336-349. doi:10.1038/s41574-023-00809-4. https://pubmed.ncbi.nlm.nih.gov/37055547/

5. Song, Ziyi, Xiaoli, Alus M, Yang, Fajun. 2018. Regulation and Metabolic Significance of De Novo Lipogenesis in Adipose Tissues. In Nutrients, 10, . doi:10.3390/nu10101383. https://pubmed.ncbi.nlm.nih.gov/30274245/

6. Hehl, Leonida, Creasy, Kate T, Vitali, Cecilia, Rader, Daniel J, Schneider, Carolin V. 2024. A genome-first approach to variants in MLXIPL and their association with hepatic steatosis and plasma lipids. In Hepatology communications, 8, . doi:10.1097/HC9.0000000000000427. https://pubmed.ncbi.nlm.nih.gov/38668731/

7. Zhan, Hongrui, Wang, Yaping, Yu, Shi, Liu, Wei, Wu, Wen. 2020. Upregulation of Mlxipl induced by cJun in the spinal dorsal horn after peripheral nerve injury counteracts mechanical allodynia by inhibiting neuroinflammation. In Aging, 12, 11004-11024. doi:10.18632/aging.103313. https://pubmed.ncbi.nlm.nih.gov/32518215/