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
Main Authors: 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
Format: Article
Language:English
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
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Summary: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.
ISSN:1422-0067
1661-6596
1422-0067
DOI:10.3390/ijms22136895