Abstract | BACKGROUND: METHODS:
Proguanylin (GUCA2A) and prouroguanylin (GUCA2B) were measured in 214 participants undergoing bariatric surgery with biopsy-proven NAFLD diagnosis. Pathways involved in lipid metabolism, mitochondrial network and fibrogenesis were evaluated in liver biopsies (n = 137). The effect of guanylin and uroguanylin on these metabolic functions was assessed in HepG2 hepatocytes and LX-2 hepatic stellate cells (HSC) under lipotoxic and profibrogenic conditions. RESULTS: Plasma and hepatic expression of GUCA2B were decreased in obesity-associated NAFLD. Both GUCA2A and GUCA2B levels were increased after sleeve gastrectomy and Roux-en-Y gastric bypass in parallel to the improved liver function. The liver of patients with type 2 diabetes showed impaired mitochondrial β-oxidation, biogenesis, dynamics as well as increased fibrosis. Uroguanylin diminished the lipotoxicity in palmitate-treated HepG2 hepatocytes, evidenced by decresased steatosis and lipogenic factors, as well as increased mitochondrial network expression, AMPK-induced β-oxidation and oxygen consumption rate. Additionally, uroguanylin, but not guanylin, reversed HSC myofibroblast transdifferentiation as well as fibrogenesis after TGF-β1 stimulation. CONCLUSIONS:
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Authors | Eva M Fernández-Sáez, Maite Losarcos, Sara Becerril, Víctor Valentí, Rafael Moncada, Marina Martín, María A Burrell, Victoria Catalán, Javier Gómez-Ambrosi, Carmen Mugueta, Inmaculada Colina, Camilo Silva, Javier Escalada, Gema Frühbeck, Amaia Rodríguez |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 147
Pg. 155663
(10 2023)
ISSN: 1532-8600 [Electronic] United States |
PMID | 37517791
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2023 The Author(s). Published by Elsevier Inc. All rights reserved. |
Chemical References |
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Topics |
- Humans
- Non-alcoholic Fatty Liver Disease
(pathology)
- Obesity, Morbid
(surgery)
- Diabetes Mellitus, Type 2
(metabolism)
- Obesity
(complications, surgery, metabolism)
- Liver
(metabolism)
- Bariatric Surgery
- Fibrosis
- Mitochondria
(metabolism)
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