SFRP5 hepatic expression is associated with non-alcoholic liver disease in morbidly obese women

Gutiérrez-Vidal, Roxana; Vega-Badillo, Joel; Reyes-Fermín, Laura María; Hernández-Pérez, Hugo A.; Sánchez‐Muñoz, Fausto; López-Álvarez, Guadalupe S.; Larrieta‐Carrasco, Elena; Fernández-Silva, Itzel; Méndez-Sánchez, Nahúm; Tovar, Armando R.; Villamil‐Ramírez, Hugo; Mejía-Domínguez, Ana María; Villarreal‐Molina, Teresa; Hernández-Pando, Rogelio; Campos-Pérez, Francisco; Aguilar-Salinas, Carlos A.; Canizales‐Quinteros, Samuel

doi:10.1016/s1665-2681(19)30761-6

Cited by 27 publications

(20 citation statements)

References 32 publications

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“…In summary, adipose specific transgenic RORα4 expression results in the differential expression of collagen genes (in SAT and liver) that are critical for ECM remodeling, and aberrant Wnt signaling - both of which are the underlying factors in altered fat deposition in adipose and hepatic tissues. This is in accord with the very recent study demonstrating the fat microenvironment controls depot specific expansion and tissue mass on obesogenic diets ( Jeffery et al, 2016 ), and obesogenic studies on Wnt signaling ( Mori et al, 2012 , Gutierrez-Vidal et al, 2015 ). Furthermore, the two gene expression profiling approaches (qPCR and RNA-seq) identified differential expression of many genes involved in lipid, and glucose homeostasis coupled to ECM remodeling, that are in accord with hepatic fibrosis as the most significantly enriched pathway in Tg-FABP4-RORα4 tg /+ SAT and liver.…”

Section: Resultssupporting

confidence: 90%

Transgenic Adipose-specific Expression of the Nuclear Receptor RORα Drives a Striking Shift in Fat Distribution and Impairs Glycemic Control

et al. 2016

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RORα is a member of the nuclear receptor (NR) superfamily and analysis of the (global) RORα-deficient mouse model revealed this NR has a role in glycemic control and fat deposition. Therefore, we generated an adipose-specific RORα ‘gain of function’ mouse model under the control of the fatty acid binding protein 4 (FABP4) promoter to elucidate the function of RORα in adipose tissue. The Tg-FABP4-RORα4 mice demonstrated a shift in fat distribution to non-adipose tissues when challenged with a high fat diet (HFD). Specifically, we observed a subcutaneous lipodystrophy, accompanied by hepatomegaly (fatty liver/mild portal fibrosis) and splenomegaly; in a background of decreased weight gain and total body fat after HFD. Moreover, we observed significantly higher fasting blood glucose and impaired clearance of glucose in Tg-FABP4-RORα4 mice. Genome wide expression and qPCR profiling analysis identified: (i) subcutaneous adipose specific decreases in the expression of genes involved in fatty acid biosynthesis, lipid droplet expansion and glycemic control, and (ii) the fibrosis pathway as the most significant pathway [including dysregulation of the collagen/extracellular matrix (ECM) pathways] in subcutaneous adipose and liver. The pathology presented in the Tg-FABP4-RORα4 mice is reminiscent of human metabolic disease (associated with aberrant ECM expression) highlighting the therapeutic potential of this NR.

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Section: Resultssupporting

confidence: 90%

Transgenic Adipose-specific Expression of the Nuclear Receptor RORα Drives a Striking Shift in Fat Distribution and Impairs Glycemic Control

et al. 2016

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“…Adiponectin, C1q/TNF-related proteins (CTRPs), omentin, and secreted frizzled-related protein 5 (SFRP5) are anti-inflammatory adipokines produced by adipose tissue. 35 – 38 Adiponectin is the best-known and most abundant adipokine found in human serum, with concentrations typically in the µg/mL range. 39 Unlike other adipokines, which are found in greatest quantities in visceral and subcutaneous adipose tissue (SCAT), it is predominantly produced by bone marrow adipose tissue (BMAT).…”

Section: Anti-inflammatory Adipokinesmentioning

confidence: 99%

The role of adipokines in chronic inflammation

Mancuso

2016

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Adipose tissue has traditionally been defined as connective tissue that stores excess calories in the form of triacylglycerol. However, the physiologic functions attributed to adipose tissue are expanding, and it is now well established that adipose tissue is an endocrine gland. Among the endocrine factors elaborated by adipose tissue are the adipokines; hormones, similar in structure to cytokines, produced by adipose tissue in response to changes in adipocyte triacylglycerol storage and local and systemic inflammation. They inform the host regarding long-term energy storage and have a profound influence on reproductive function, blood pressure regulation, energy homeostasis, the immune response, and many other physiologic processes. The adipokines possess pro- and anti-inflammatory properties and play a critical role in integrating systemic metabolism with immune function. In calorie restriction and starvation, proinflammatory adipokines decline and anti-inflammatory adipokines increase, which informs the host of energy deficits and contributes to the suppression of immune function. In individuals with normal metabolic status, there is a balance of pro- and anti-inflammatory adipokines. This balance shifts to favor proinflammatory mediators as adipose tissue expands during the development of obesity. As a consequence, the proinflammatory status of adipose tissue contributes to a chronic low-grade state of inflammation and metabolic disorders associated with obesity. These disturbances are associated with an increased risk of metabolic disease, type 2 diabetes, cardiovascular disease, and many other pathological conditions. This review focuses on the impact of energy homeostasis on the adipokines in immune function.

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“…Serum SFRP5 level of diabetic patients with obesity is lower than normal subjects, while GLP-1 agonist liraglutide intervention results in weight loss and serum SFRP5 elevation [ 10 ]. SFRP5 protein levels were significantly lower in NASH than in control subjects [ 11 ]. SFRP5 knockout mice develop obesity and adipose inflammation [ 9 , 12 ], while SFRP5 overexpression via adenovirus could alleviate obesity, adipose inflammation and hepatosteatosis.…”

Section: Introductionmentioning

confidence: 99%

Recombinant SFRP5 protein significantly alleviated intrahepatic inflammation of nonalcoholic steatohepatitis

et al. 2017

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BackgroundSecreted frizzled-related protein 5 (SFRP5) is an anti-inflammatory adipokine modulating metabolism dysfunction. This study aims to observe the effect of recombinant SFRP5 protein on nonalcoholic steatohepatitis (NASH).MethodsWe set up a prokaryotic expression system and purified the recombinant SFRP5 protein. Recombinant SFRP5 protein was further identified by SDS-PAGE, western blot, high performance liquid chromatography (HPLC), protein mass spectrometry and in vitro Wnt5a-binding test. NASH mouse model was induced by methionine and choline deficient diet (MCDD) for 2 weeks. SFRP5 treatment group received intraperitoneal injection with a dosage of 10μg/kg SFRP5 twice a day for 2 weeks. Saline was used as control. Inflammation and fatty lesion score of liver tissue pathology and serum transaminase level were compared.ResultsThe purity of recombinant SFRP5 protein is 90% identified by HPLC. Its molecule size is 36,096.08 tested by mass spectrometry. Recombinant SFRP5 can specifically bind with Wnt5a which verifies its activity in vitro. The endotoxin level of this recombinant protein is 0.01EU/μg-0.1EU/μg and is suitable for animal experiment. SFRP5 can significantly improve liver inflammation (SFRP5 vs. control, 1.40 ± 0.70 vs. 2.00 ± 0.47, P < 0.05) as well as fatty lesion scores (SFRP5 vs. control, 1.40 ± 0.97 vs. 2.20 ± 0.63, P < 0.05), and lower ALT and AST levels. The mRNA expression of proinflammatory adipokines (IL-1β, IL-6, TNFα and MCP-1) in liver was down-regulated significantly after SFRP5 intervention. Immunohistochemistry and quantitative PCR revealed a dramatically down-regulation of F4/80 in liver after SFRP5 treatment.ConclusionsRecombinant SFRP5 protein significantly alleviated NASH induced by MCDD.Electronic supplementary materialThe online version of this article (doi:10.1186/s12986-017-0208-0) contains supplementary material, which is available to authorized users.

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SFRP5 hepatic expression is associated with non-alcoholic liver disease in morbidly obese women

Cited by 27 publications

References 32 publications

Transgenic Adipose-specific Expression of the Nuclear Receptor RORα Drives a Striking Shift in Fat Distribution and Impairs Glycemic Control

Transgenic Adipose-specific Expression of the Nuclear Receptor RORα Drives a Striking Shift in Fat Distribution and Impairs Glycemic Control

The role of adipokines in chronic inflammation

Recombinant SFRP5 protein significantly alleviated intrahepatic inflammation of nonalcoholic steatohepatitis

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