Effects of intestine-specific deletion of FGF15 on the development of fatty liver disease with vertical sleeve gastrectomy.

Autor:	Chow MD; Department of Surgery, Division of Pediatric Surgery, Rutgers Robert Wood Johnson Medical Center School, New Brunswick, New Jersey, USA., Otersen K; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Wassef A; Department of Pharmaceutics, Ernest Mario School of Pharmacy-Rutgers University, Piscataway, New Jersey, USA.; Center of Excellence for Pharmaceutical Translational Research and Education, Rutgers University, Piscataway, New Jersey, USA.; Center of Excellence for Metabolic and Bariatric Surgery, Robert Wood Johnson Barnabas University Hospital, New Brunswick, New Jersey, USA.; Advanced Surgical & Bariatrics of NJ, Somerset, New Jersey, USA., Kong B; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Yamarthy S; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Rizzolo D; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Yang I; Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA., Buckley B; Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA., Lu A; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Crook N; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Lee M; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Gao J; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Naganand S; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Stofan MF; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Armstrong L; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Schumacher J; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Taylor R; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Henry Z; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Basaly V; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Yang Z; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA., Zhang M; Children's Liver Disease Center, 302 Military Hospital, Beijing, China., Huang M; Department of Infectious Diseases, the Fifth Affiliated Hospital of Sun Yat-Sen University (SYSU), Zhuhai, Guangdong, China., Kagan L; Department of Pharmaceutics, Ernest Mario School of Pharmacy-Rutgers University, Piscataway, New Jersey, USA.; Center of Excellence for Pharmaceutical Translational Research and Education, Rutgers University, Piscataway, New Jersey, USA., Brunetti L; Department of Pharmaceutics, Ernest Mario School of Pharmacy-Rutgers University, Piscataway, New Jersey, USA.; Center of Excellence for Pharmaceutical Translational Research and Education, Rutgers University, Piscataway, New Jersey, USA., Sadek R; Center of Excellence for Metabolic and Bariatric Surgery, Robert Wood Johnson Barnabas University Hospital, New Brunswick, New Jersey, USA.; Advanced Surgical & Bariatrics of NJ, Somerset, New Jersey, USA., Lee YH; Department of Surgery, Division of Pediatric Surgery, Rutgers Robert Wood Johnson Medical Center School, New Brunswick, New Jersey, USA., Guo GL; Department of Pharmacology and Toxicology, Rutgers University, Piscataway, New Jersey, USA.; Environmental and Occupational Health Science Institute, Rutgers University, Piscataway, New Jersey, USA.; Department of Veterans Affairs New Jersey Health Care System, East Orange, New Jersey, USA.; Rutgers Center for Lipid Research, New Brunswick, New Jersey, USA.
Jazyk:	angličtina
Zdroj:	Hepatology communications [Hepatol Commun] 2024 May 22; Vol. 8 (6). Date of Electronic Publication: 2024 May 22 (Print Publication: 2024).
DOI:	10.1097/HC9.0000000000000444
Abstrakt:	Background: Vertical sleeve gastrectomy (SGx) is a type of bariatric surgery to treat morbid obesity and metabolic dysfunction-associated steatotic liver disease (MASLD). The molecular mechanisms of SGx to improve MASLD are unclear, but increased bile acids (BAs) and FGF19 (mouse FGF15) were observed. FGF15/19 is expressed in the ileum in response to BAs and is critical in not only suppressing BA synthesis in the liver but also promoting energy expenditure. We hypothesized the reduction of obesity and resolution of MASLD by SGx may be mediated by FGF15/19. Methods: First, we conducted hepatic gene expression analysis in obese patients undergoing SGx, with the results showing increased expression of FGF19 in obese patients' livers. Next, we used wild-type and intestine-specific Fgf15 knockout mice (Fgf15ile-/-) to determine the effects of FGF15 deficiency on improving the metabolic effects. Results: SGx improved metabolic endpoints in both genotypes, evidenced by decreased obesity, improved glucose tolerance, and reduced MASLD progression. However, Fgf15ile-/- mice showed better improvement compared to wild-type mice after SGx, suggesting that other mediators than FGF15 are also responsible for the beneficial effects of FGF15 deficiency. Further gene expression analysis in brown adipose tissue suggests increased thermogenesis. Conclusions: FGF15 deficiency, the larger BA pool and higher levels of secondary BAs may increase energy expenditure in extrahepatic tissues, which may be responsible for improved metabolic functions following SGx. (Copyright © 2024 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the American Association for the Study of Liver Diseases.)
Databáze:	MEDLINE
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