Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery
IntroductionObesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and β-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of...
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Frontiers Media S.A.
2023-05-01
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| Series: | Frontiers in Endocrinology |
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| author | Aarón Otero Sara Becerril Sara Becerril Sara Becerril Marina Martín Javier A. Cienfuegos Javier A. Cienfuegos Javier A. Cienfuegos Víctor Valentí Víctor Valentí Víctor Valentí Rafael Moncada Rafael Moncada Rafael Moncada Victoria Catalán Victoria Catalán Victoria Catalán Javier Gómez-Ambrosi Javier Gómez-Ambrosi Javier Gómez-Ambrosi María A. Burrell María A. Burrell María A. Burrell Gema Frühbeck Gema Frühbeck Gema Frühbeck Gema Frühbeck Amaia Rodríguez Amaia Rodríguez Amaia Rodríguez |
| author_facet | Aarón Otero Sara Becerril Sara Becerril Sara Becerril Marina Martín Javier A. Cienfuegos Javier A. Cienfuegos Javier A. Cienfuegos Víctor Valentí Víctor Valentí Víctor Valentí Rafael Moncada Rafael Moncada Rafael Moncada Victoria Catalán Victoria Catalán Victoria Catalán Javier Gómez-Ambrosi Javier Gómez-Ambrosi Javier Gómez-Ambrosi María A. Burrell María A. Burrell María A. Burrell Gema Frühbeck Gema Frühbeck Gema Frühbeck Gema Frühbeck Amaia Rodríguez Amaia Rodríguez Amaia Rodríguez |
| author_sort | Aarón Otero |
| collection | DOAJ |
| description | IntroductionObesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and β-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery.MethodsPancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F β-cells exposed to lipotoxic conditions.ResultsSleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with diet-induced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F β-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F β-cells, but only guanylin upregulated Wnt4, a factor that controls β-cell proliferation and function.DiscussionTogether, sleeve gastrectomy reduced pancreatic steatosis and improved β-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery. |
| first_indexed | 2024-03-13T10:34:15Z |
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| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-13T10:34:15Z |
| publishDate | 2023-05-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-a67e37be52534e13972180aa549273c82023-05-18T07:58:27ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-05-011410.3389/fendo.2023.11854561185456Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgeryAarón Otero0Sara Becerril1Sara Becerril2Sara Becerril3Marina Martín4Javier A. Cienfuegos5Javier A. Cienfuegos6Javier A. Cienfuegos7Víctor Valentí8Víctor Valentí9Víctor Valentí10Rafael Moncada11Rafael Moncada12Rafael Moncada13Victoria Catalán14Victoria Catalán15Victoria Catalán16Javier Gómez-Ambrosi17Javier Gómez-Ambrosi18Javier Gómez-Ambrosi19María A. Burrell20María A. Burrell21María A. Burrell22Gema Frühbeck23Gema Frühbeck24Gema Frühbeck25Gema Frühbeck26Amaia Rodríguez27Amaia Rodríguez28Amaia Rodríguez29Metabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainDepartment of Pathology, Anatomy and Physiology, University of Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainDepartment of Surgery, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainDepartment of Surgery, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainDepartment of Anesthesia, Clínica Universidad de Navarra, Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainDepartment of Pathology, Anatomy and Physiology, University of Navarra, Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainDepartment of Endocrinology and Nutrition, Clínica Universidad de Navarra, Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, Madrid, SpainObesity and Adipobiology Group, Instituto de Investigación Sanitaria de Navarra (IdiSNA), Pamplona, SpainIntroductionObesity contributes to ectopic fat deposition in non-adipose organs, including the pancreas. Pancreas steatosis associates with inflammation and β-cell dysfunction, contributing to the onset of insulin resistance and type 2 diabetes. An improvement of pancreatic steatosis and indices of insulin resistance is observed following bariatric surgery, but the underlying mechanisms remain unknown. We sought to analyze whether guanylin (GUCA2A) and uroguanylin (GUCA2B), two gut hormones involved in the regulation of satiety, food preference and adiposity, are involved in the amelioration of pancreas fat accumulation after bariatric surgery.MethodsPancreas steatosis, inflammation, islet number and area were measured in male Wistar rats with diet-induced obesity (n=125) subjected to surgical (sham operation and sleeve gastrectomy) or dietary (pair-fed to the amount of food eaten by gastrectomized animals) interventions. The tissue distribution of guanylate cyclase C (GUCY2C) and the expression of the guanylin system were evaluated in rat pancreata by real-time PCR, Western-blot and immunohistochemistry. The effect of guanylin and uroguanylin on factors involved in insulin secretion and lipogenesis was determined in vitro in RIN-m5F β-cells exposed to lipotoxic conditions.ResultsSleeve gastrectomy reduced pancreas steatosis and inflammation and improved insulin sensitivity and synthesis. An upregulation of GUCA2A and GUCY2C, but not GUCA2B, was observed in pancreata from rats with diet-induced obesity one month after sleeve gastrectomy. Interestingly, both guanylin and uroguanylin diminished the lipotoxicity in palmitate-treated RIN-m5F β-cells, evidenced by lower steatosis and downregulated lipogenic factors Srebf1, Mogat2 and Dgat1. Both guanylin peptides reduced insulin synthesis (Ins1 and Ins2) and release from RIN-m5F β-cells, but only guanylin upregulated Wnt4, a factor that controls β-cell proliferation and function.DiscussionTogether, sleeve gastrectomy reduced pancreatic steatosis and improved β-cell function. Several mechanisms, including the modulation of inflammation and lipogenesis as well as the upregulation of GUCA2A in the pancreas, might explain this beneficial effect of bariatric surgery.https://www.frontiersin.org/articles/10.3389/fendo.2023.1185456/fulluroguanylinguanylinguanylate cyclase 2Cβ-cell functionlipogenesis |
| spellingShingle | Aarón Otero Sara Becerril Sara Becerril Sara Becerril Marina Martín Javier A. Cienfuegos Javier A. Cienfuegos Javier A. Cienfuegos Víctor Valentí Víctor Valentí Víctor Valentí Rafael Moncada Rafael Moncada Rafael Moncada Victoria Catalán Victoria Catalán Victoria Catalán Javier Gómez-Ambrosi Javier Gómez-Ambrosi Javier Gómez-Ambrosi María A. Burrell María A. Burrell María A. Burrell Gema Frühbeck Gema Frühbeck Gema Frühbeck Gema Frühbeck Amaia Rodríguez Amaia Rodríguez Amaia Rodríguez Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery Frontiers in Endocrinology uroguanylin guanylin guanylate cyclase 2C β-cell function lipogenesis |
| title | Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery |
| title_full | Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery |
| title_fullStr | Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery |
| title_full_unstemmed | Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery |
| title_short | Effect of guanylin peptides on pancreas steatosis and function in experimental diet-induced obesity and after bariatric surgery |
| title_sort | effect of guanylin peptides on pancreas steatosis and function in experimental diet induced obesity and after bariatric surgery |
| topic | uroguanylin guanylin guanylate cyclase 2C β-cell function lipogenesis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1185456/full |
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