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Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity
Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determi...
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Published in: | International journal of molecular sciences 2021-07, Vol.22 (13), p.6895 |
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creator | Bertran, Laia Portillo-Carrasquer, Marta Aguilar, Carmen Porras, José Antonio Riesco, David Martínez, Salomé Vives, Margarita Sabench, Fàtima Gonzalez, Eva Del Castillo, Daniel Richart, Cristóbal Auguet, Teresa |
description | Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage. |
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The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. In conclusion, circulating SFRP5 levels depend on the diet, and hepatic SFRP5 seems to have a protective role in the first steps of NAFLD; however, SFRP5 could be deregulated in an advanced stage while WNT5A and JNK are activated, promoting liver damage.</description><identifier>ISSN: 1422-0067</identifier><identifier>ISSN: 1661-6596</identifier><identifier>EISSN: 1422-0067</identifier><identifier>DOI: 10.3390/ijms22136895</identifier><identifier>PMID: 34198988</identifier><language>eng</language><publisher>Basel: MDPI AG</publisher><subject>Blood pressure ; Body mass index ; Cholesterol ; Deregulation ; Fatty liver ; Frizzled protein ; Frizzled-related protein ; Gene expression ; Glucose ; Histology ; Hypocaloric diet ; Inflammation ; Insulin resistance ; Kinases ; Liver ; Liver diseases ; Metabolism ; nonalcoholic fatty liver disease ; noncanonical WNT pathway ; Nutrient deficiency ; Obesity ; Pathogenesis ; Patients ; Phosphorylation ; Proteins ; SFRP5 ; Steatosis ; Wnt protein ; Womens health</subject><ispartof>International journal of molecular sciences, 2021-07, Vol.22 (13), p.6895</ispartof><rights>2021 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.</rights><rights>2021 by the authors. 2021</rights><lds50>peer_reviewed</lds50><oa>free_for_read</oa><woscitedreferencessubscribed>false</woscitedreferencessubscribed><citedby>FETCH-LOGICAL-c455t-ecea84146bd54687ff0f6e16b8602847aaff5291fdfe8bdd47ca6250112a98f53</citedby><cites>FETCH-LOGICAL-c455t-ecea84146bd54687ff0f6e16b8602847aaff5291fdfe8bdd47ca6250112a98f53</cites><orcidid>0000-0003-0396-6428 ; 0000-0001-9052-1368 ; 0000-0001-6167-9801</orcidid></display><links><openurl>$$Topenurl_article</openurl><openurlfulltext>$$Topenurlfull_article</openurlfulltext><thumbnail>$$Tsyndetics_thumb_exl</thumbnail><linktopdf>$$Uhttps://www.proquest.com/docview/2549398385/fulltextPDF?pq-origsite=primo$$EPDF$$P50$$Gproquest$$Hfree_for_read</linktopdf><linktohtml>$$Uhttps://www.proquest.com/docview/2549398385?pq-origsite=primo$$EHTML$$P50$$Gproquest$$Hfree_for_read</linktohtml><link.rule.ids>230,314,727,780,784,885,25753,27924,27925,37012,37013,44590,53791,53793,75126</link.rule.ids></links><search><creatorcontrib>Bertran, Laia</creatorcontrib><creatorcontrib>Portillo-Carrasquer, Marta</creatorcontrib><creatorcontrib>Aguilar, Carmen</creatorcontrib><creatorcontrib>Porras, José Antonio</creatorcontrib><creatorcontrib>Riesco, David</creatorcontrib><creatorcontrib>Martínez, Salomé</creatorcontrib><creatorcontrib>Vives, Margarita</creatorcontrib><creatorcontrib>Sabench, Fàtima</creatorcontrib><creatorcontrib>Gonzalez, Eva</creatorcontrib><creatorcontrib>Del Castillo, Daniel</creatorcontrib><creatorcontrib>Richart, Cristóbal</creatorcontrib><creatorcontrib>Auguet, Teresa</creatorcontrib><title>Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity</title><title>International journal of molecular sciences</title><description>Secreted frizzled-related protein 5 (SFRP5), an antagonist of the noncanonical WNT pathway, has a controversial role in liver disease. The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. 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The aim of this study was to analyze the role of SFRP5 and the noncanonical WNT pathway in nonalcoholic fatty liver disease (NAFLD). Plasma SFRP5 levels were determined by ELISA in women with normal weight (NW; n = 20) and morbid obesity (MO; n = 69). Women with MO were subclassified according to hepatic histology into normal liver (NL; n = 28), NAFLD (n = 41) (simple steatosis (SS; n = 24), and nonalcoholic steatohepatitis (NASH; n = 17)). We used RT-qPCR to evaluate the hepatic mRNA expression of SFRP5, WNT5A, and JNK in women with MO. SFRP5 levels were lower in NW than in MO patients who underwent a very low-calorie diet before surgery. Hepatic SFRP5 mRNA expression was higher in SS than in NL or NASH; additionally, patients with hepatic inflammation or ballooning presented lower SFRP5 abundance. WNT5A and JNK expression was enhanced in NAFLD compared with NL. 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subjects | Blood pressure Body mass index Cholesterol Deregulation Fatty liver Frizzled protein Frizzled-related protein Gene expression Glucose Histology Hypocaloric diet Inflammation Insulin resistance Kinases Liver Liver diseases Metabolism nonalcoholic fatty liver disease noncanonical WNT pathway Nutrient deficiency Obesity Pathogenesis Patients Phosphorylation Proteins SFRP5 Steatosis Wnt protein Womens health |
title | Deregulation of Secreted Frizzled-Related Protein 5 in Nonalcoholic Fatty Liver Disease Associated with Obesity |
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