FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummary
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 alle...
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| Format: | Article |
| Language: | English |
| Published: |
Elsevier
2022-01-01
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| Series: | Cellular and Molecular Gastroenterology and Hepatology |
| Subjects: | |
| Online Access: | http://www.sciencedirect.com/science/article/pii/S2352345X22000170 |
| _version_ | 1818017910154592256 |
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| author | Yun Cheng Xiao-Zhuo Kang Tao Cheng Zi-Wei Ye George L. Tipoe Cheng-Han Yu Chi-Ming Wong Baohua Liu Chi-Ping Chan Dong-Yan Jin |
| author_facet | Yun Cheng Xiao-Zhuo Kang Tao Cheng Zi-Wei Ye George L. Tipoe Cheng-Han Yu Chi-Ming Wong Baohua Liu Chi-Ping Chan Dong-Yan Jin |
| author_sort | Yun Cheng |
| collection | DOAJ |
| description | 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 clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (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 sterol regulatory element-binding protein 1 (SREBP1), hepatocyte nuclear factor 4α (HNF4α), peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α), and CREB, as well as fasting-related cyclic adenosine monophosphate (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. |
| first_indexed | 2024-04-14T07:32:57Z |
| format | Article |
| id | doaj.art-65f7c34b967c48b69376d855a28bcaa9 |
| institution | Directory Open Access Journal |
| issn | 2352-345X |
| language | English |
| last_indexed | 2024-04-14T07:32:57Z |
| publishDate | 2022-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Cellular and Molecular Gastroenterology and Hepatology |
| spelling | doaj.art-65f7c34b967c48b69376d855a28bcaa92022-12-22T02:05:48ZengElsevierCellular and Molecular Gastroenterology and Hepatology2352-345X2022-01-0113513651391FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummaryYun Cheng0Xiao-Zhuo Kang1Tao Cheng2Zi-Wei Ye3George L. Tipoe4Cheng-Han Yu5Chi-Ming Wong6Baohua Liu7Chi-Ping Chan8Dong-Yan Jin9School of Biomedical Sciences, Pokfulam, Hong Kong; State Key Laboratory of Liver Research, Pokfulam, Hong Kong; Correspondence Address correspondence to: Dong-Yan Jin, or Yun Cheng, PhD, School of Biomedical Sciences, The University of Hong Kong, 3/F Lab Block, 21 Sassoon Road, Pokfulam, Hong Kong. fax: (852) 28551254.School of Biomedical Sciences, Pokfulam, Hong Kong; State Key Laboratory of Liver Research, Pokfulam, Hong KongSchool of Biomedical Sciences, Pokfulam, Hong Kong; State Key Laboratory of Liver Research, Pokfulam, Hong KongDepartment of Microbiology, The University of Hong Kong, Pokfulam, Hong KongSchool of Biomedical Sciences, Pokfulam, Hong KongSchool of Biomedical Sciences, Pokfulam, Hong KongDepartment of Health Technology and Informatics, The Hong Kong Polytechnic University, Hung Hom, Kowloon, Hong KongDepartment of Biochemistry and Molecular Biology, Shenzhen University Health Science Center, Shenzhen, ChinaSchool of Biomedical Sciences, Pokfulam, Hong Kong; State Key Laboratory of Liver Research, Pokfulam, Hong KongSchool of Biomedical Sciences, Pokfulam, Hong Kong; State Key Laboratory of Liver Research, Pokfulam, Hong Kong; Correspondence Address correspondence to: Dong-Yan Jin, or Yun Cheng, PhD, School of Biomedical Sciences, The University of Hong Kong, 3/F Lab Block, 21 Sassoon Road, Pokfulam, Hong Kong. fax: (852) 28551254.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 clustered regularly interspaced short palindromic repeats (CRISPR)/CRISPR-associated 9 (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 sterol regulatory element-binding protein 1 (SREBP1), hepatocyte nuclear factor 4α (HNF4α), peroxisome proliferator-activated receptor γ coactivator-1α (PGC1α), and CREB, as well as fasting-related cyclic adenosine monophosphate (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.http://www.sciencedirect.com/science/article/pii/S2352345X22000170Lipid HomeostasisPhospholipid-Binding ProteinRecycling EndosomeIntestinal Fat AbsorptionMetabolic Syndrome |
| spellingShingle | Yun Cheng Xiao-Zhuo Kang Tao Cheng Zi-Wei Ye George L. Tipoe Cheng-Han Yu Chi-Ming Wong Baohua Liu Chi-Ping Chan Dong-Yan Jin FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummary Cellular and Molecular Gastroenterology and Hepatology Lipid Homeostasis Phospholipid-Binding Protein Recycling Endosome Intestinal Fat Absorption Metabolic Syndrome |
| title | FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummary |
| title_full | FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummary |
| title_fullStr | FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummary |
| title_full_unstemmed | FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummary |
| title_short | FACI Is a Novel CREB-H–Induced Protein That Inhibits Intestinal Lipid Absorption and Reverses Diet-Induced ObesitySummary |
| title_sort | faci is a novel creb h induced protein that inhibits intestinal lipid absorption and reverses diet induced obesitysummary |
| topic | Lipid Homeostasis Phospholipid-Binding Protein Recycling Endosome Intestinal Fat Absorption Metabolic Syndrome |
| url | http://www.sciencedirect.com/science/article/pii/S2352345X22000170 |
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