| First Author | Cheng Y | Year | 2022 |
| Journal | Cell Mol Gastroenterol Hepatol | Volume | 13 |
| Issue | 5 | Pages | 1365-1391 |
| PubMed ID | 35093589 | Mgi Jnum | J:326325 |
| Mgi Id | MGI:6885849 | Doi | 10.1016/j.jcmgh.2022.01.017 |
| Citation | Cheng Y, et al. (2022) FACI Is a Novel CREB-H-Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced Obesity. Cell Mol Gastroenterol Hepatol |
| abstractText | BACKGROUND & AIMS: CREB-H is a key liver-enriched transcription factor governing lipid metabolism. Additional targets of CREB-H remain to be identified and characterized. Here, we identified a novel fasting- and CREB-H-induced (FACI) protein that inhibits intestinal lipid absorption and alleviates diet-induced obesity in mice. METHODS: FACI was identified by reanalysis of existing transcriptomic data. Faci(-/-) mice were generated by CRISPR/Cas9-mediated genome engineering. RNA sequencing was performed to identify differentially expressed genes in Faci(-/-) mice. Lipid accumulation in the villi was assessed by triglyceride measurement and Oil red O staining. In vitro fatty acid uptake assay was performed to verify in vivo findings. RESULTS: FACI expression was enriched in liver and intestine. FACI is a phospholipid-binding protein that localizes to plasma membrane and recycling endosomes. Hepatic transcription of Faci was regulated by not only CREB-H, but also nutrient-responsive transcription factors SREBP1, HNF4alpha, PGC1alpha, and CREB, as well as fasting-related cAMP signaling. Genetic knockout of Faci in mice showed an increase in intestinal fat absorption. In accordance with this, Faci deficiency aggravated high-fat diet-induced obesity, hyperlipidemia, steatosis, and other obesity-related metabolic dysfunction in mice. CONCLUSIONS: FACI is a novel CREB-H-induced protein. Genetic disruption of Faci in mice showed its inhibitory effect on fat absorption and obesity. Our findings shed light on a new target of CREB-H implicated in lipid homeostasis. |
