MLXIPL, also known as carbohydrate-responsive element-binding protein, is an important regulator of glucolipid metabolism [2,6]. It is involved in pathways related to lipogenesis, such as the transcriptional regulation of lipogenic genes [3]. Dysregulation of these processes can contribute to diseases like hepatosteatosis, obesity, and type 2 diabetes, highlighting its biological importance [3,4,5]. Genetic models could potentially be used to further study its function.

In prostate cancer, MLXIPL expressed in response to tumor-infiltrating CD8+ T cells is associated with a poor prognosis [1]. In hepatocellular carcinoma, MLXIPL levels are elevated, and its knockdown impedes cell growth, invasion, migration, and glycolysis. It promotes the malignant progression of HCC by phosphorylating mTOR [2]. A missense variant in MLXIPL, Gln241His, is associated with various lipid-related phenotypes and a higher risk of steatotic liver disease, especially in certain subgroups [6]. In the spinal dorsal horn after peripheral nerve injury, upregulation of Mlxipl induced by cJun inhibits mechanical allodynia and neuroinflammation [7].

In summary, MLXIPL plays crucial roles in glucolipid metabolism and is involved in multiple disease conditions including cancer and neuropathic pain. Studies, though not specifically from KO/CKO mouse models in the provided references, have revealed its functions in disease-related biological processes, contributing to our understanding of these diseases and potentially paving the way for targeted therapies.

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/