Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity
Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental...
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MDPI AG
2021-11-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/22/23/12945 |
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| author | Carolina M. Perdomo Javier Gómez-Ambrosi Sara Becerril Víctor Valentí Rafael Moncada Eva M. Fernández-Sáez Leire Méndez-Giménez Silvia Ezquerro Victoria Catalán Camilo Silva Javier Escalada Gema Frühbeck Amaia Rodríguez |
| author_facet | Carolina M. Perdomo Javier Gómez-Ambrosi Sara Becerril Víctor Valentí Rafael Moncada Eva M. Fernández-Sáez Leire Méndez-Giménez Silvia Ezquerro Victoria Catalán Camilo Silva Javier Escalada Gema Frühbeck Amaia Rodríguez |
| author_sort | Carolina M. Perdomo |
| collection | DOAJ |
| description | Angiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (<i>n</i> = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (<i>n</i> = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (<i>PPARG2</i>, <i>SREBF1</i>, <i>MOGAT2</i> and <i>DGAT1</i>) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes. |
| first_indexed | 2024-03-10T04:52:31Z |
| format | Article |
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| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-10T04:52:31Z |
| publishDate | 2021-11-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-9f9fc1df6f744a66b1f78bf7c91dff4e2023-11-23T02:30:47ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672021-11-0122231294510.3390/ijms222312945Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human ObesityCarolina M. Perdomo0Javier Gómez-Ambrosi1Sara Becerril2Víctor Valentí3Rafael Moncada4Eva M. Fernández-Sáez5Leire Méndez-Giménez6Silvia Ezquerro7Victoria Catalán8Camilo Silva9Javier Escalada10Gema Frühbeck11Amaia Rodríguez12Department of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, SpainCIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Instituto de Salud Carlos III, 28029 Madrid, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainMetabolic Research Laboratory, Clínica Universidad de Navarra, 31008 Pamplona, SpainDepartment of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, SpainDepartment of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, SpainDepartment of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, SpainDepartment of Endocrinology & Nutrition, Clínica Universidad de Navarra, 31008 Pamplona, SpainAngiopoietin-like protein 8 (ANGPTL8) is an hepatokine altered in several metabolic conditions, such as obesity, type 2 diabetes, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). We sought to explore whether ANGPTL8 is involved in NAFLD amelioration after bariatric surgery in experimental models and patients with severe obesity. Plasma ANGPTL8 was measured in 170 individuals before and 6 months after bariatric surgery. Hepatic ANGPTL8 expression was evaluated in liver biopsies of patients with severe obesity undergoing bariatric surgery with available liver pathology analysis (<i>n</i> = 75), as well as in male Wistar rats with diet-induced obesity subjected to sham operation, sleeve gastrectomy or Roux-en-Y gastric bypass (RYGB) (<i>n</i> = 65). The effect of ANGPTL8 on lipogenesis was assessed in human HepG2 hepatocytes under palmitate-induced lipotoxic conditions. Plasma concentrations and hepatic expression of ANGPTL8 were increased in patients with obesity-associated NAFLD in relation to the degree of hepatic steatosis. Sleeve gastrectomy and RYGB improved hepatosteatosis and reduced the hepatic ANGPTL8 expression in the preclinical model of NAFLD. Interestingly, ANGPTL8 inhibited steatosis and expression of lipogenic factors (<i>PPARG2</i>, <i>SREBF1</i>, <i>MOGAT2</i> and <i>DGAT1</i>) in palmitate-treated human hepatocytes. Together, ANGPTL8 is involved in the resolution of NAFLD after bariatric surgery partially by the inhibition of lipogenesis in steatotic hepatocytes.https://www.mdpi.com/1422-0067/22/23/12945NAFLDobesitybariatric surgerylipogenesisangiopoietin-like protein 8 |
| spellingShingle | Carolina M. Perdomo Javier Gómez-Ambrosi Sara Becerril Víctor Valentí Rafael Moncada Eva M. Fernández-Sáez Leire Méndez-Giménez Silvia Ezquerro Victoria Catalán Camilo Silva Javier Escalada Gema Frühbeck Amaia Rodríguez Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity International Journal of Molecular Sciences NAFLD obesity bariatric surgery lipogenesis angiopoietin-like protein 8 |
| title | Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity |
| title_full | Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity |
| title_fullStr | Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity |
| title_full_unstemmed | Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity |
| title_short | Role of ANGPTL8 in NAFLD Improvement after Bariatric Surgery in Experimental and Human Obesity |
| title_sort | role of angptl8 in nafld improvement after bariatric surgery in experimental and human obesity |
| topic | NAFLD obesity bariatric surgery lipogenesis angiopoietin-like protein 8 |
| url | https://www.mdpi.com/1422-0067/22/23/12945 |
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