Fndc4, a highly identical ortholog of Irisin binds and activates a novel orphan receptor G-protein coupled receptor

Georgiadi, Anastasia; Ma, Xiaochuan; Bosma, Madeleen; Graham, E; Shilkova, Olga; Mattijssen, Frits; Aa, Khan; Higareda, Jca; Wünsch, T; Johansson, Martin; Seaman, Steven; Croix, BS; Ritvos, Olli; Nakamura, Noriko; Hirose, Shintaro; Scheideler, Mark A.; Herzig, Stephan; Boström, P

doi:10.1055/s-0036-1580814

Cited by 2 publications

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“…It has also been shown to inhibit osteoclast formation via the suppression of NF- κ B and downregulation of CXCL10 [35]. Another FNDC4 receptor candidate was supposed by Georgiadi et al, who found that FNDC4 binds to GPR116 [20]. In our analysis, GPR116 was not significantly regulated in IBD samples.…”

Section: Discussionmentioning

confidence: 45%

“…The exact receptor or binding partner to facilitate downstream signaling is, so far, not fully understood. However, Georgiadi et al revealed in an in vitro binding study the orphan G-protein-coupled receptor 116 ( GPR116 ) as a putative functional FNDC4 receptor candidate [20]. GPR116 is expressed in various tissues, including lung, kidney, or fat, and it has been described to be overexpressed in metastatic colorectal cancer (CRC) or breast cancer [21, 22].…”

Section: Introductionmentioning

confidence: 99%

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Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer

Wuensch

Wizenty

Quint

et al. 2019

Gastroenterology Research and Practice

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Background. Fibronectin type III domain-containing (FNDC) proteins fulfill manifold functions in tissue development and regulation of cellular metabolism. FNDC4 was described as anti-inflammatory factor, upregulated in inflammatory bowel disease (IBD). FNDC signaling includes direct cell-cell interaction as well as release of bioactive peptides, like shown for FNDC4 or FNDC5. The G-protein-coupled receptor 116 (GPR116) was found as a putative FNDC4 receptor. We here aim to comprehensively analyze the mRNA expression of FNDC1, FNDC3A, FNDC3B, FNDC4, FNDC5, and GPR116 in nonaffected and affected mucosal samples of patients with IBD or colorectal cancer (CRC). Methods. Mucosa samples were obtained from 30 patients undergoing diagnostic colonoscopy or from surgical resection of IBD or CRC. Gene expression was determined by quantitative real-time PCR. In addition, FNDC expression data from publicly available Gene Expression Omnibus (GEO) data sets (GDS4296, GDS4515, and GDS5232) were analyzed. Results. Basal mucosal expression revealed higher expression of FNDC3A and FNDC5 in the ileum compared to colonic segments. FNDC1 and FNDC4 were significantly upregulated in IBD. None of the investigated FNDCs was differentially expressed in CRC, just FNDC3A trended to be upregulated. The GEO data set analysis revealed significantly downregulated FNDC4 and upregulated GPR116 in microsatellite unstable (MSI) CRCs. The expression of FNDCs and GPR116 was independent of age and sex. Conclusions. FNDC1 and FNDC4 may play a relevant role in the pathobiology of IBD, but none of the investigated FNDCs is regulated in CRC. GPR116 may be upregulated in advanced or MSI CRC. Further studies should validate the altered FNDC expression results on protein levels and examine the corresponding functional consequences.

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Section: Discussionmentioning

confidence: 45%

Section: Introductionmentioning

confidence: 99%

Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer

Wuensch

Wizenty

Quint

et al. 2019

Gastroenterology Research and Practice

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“…Similarly to FNDC5, FNDC4 is cleaved and releases a functional active peptide in the bloodstream that has recently been identified as an adipokine in humans ( 40 ). Abundance of FNDC4 mRNA is elevated in adipose tissue of obese patients, and exogenous FNDC4 inhibited lipogenesis in human visceral adipocytes in vitro through the adhesion G-protein-coupled receptor F5 [ADGRF5, also known as G-protein-coupled receptor 116 (GPR116)] ( 40 , 41 ) and upregulates UCP1 as well as FNDC5 ( 40 ).…”

Section: Introductionmentioning

confidence: 99%

Impact of fibronectin type III domain-containing family in the changes in metabolic and hormonal profiles during peripartum period in dairy cows

et al. 2022

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The peripartum period in dairy cows is frequently associated with excessive lipolysis due to Negative Energy Balance (NEB). These metabolic disorders are the cause of various pathologies. Some metabolites such as β-hydroxybutyrate (BHBA) and Non-Esterified Fatty Acids (NEFA) are known to be biomarkers of NEB in dairy cows. The involvement of adipokines, including adiponectin and leptin, during fat mobilization in the peripartum period is well described, but little is known about the impact of myokines at this time. Fibronectin type III domain-containing proteins (FNDC) are myokines and adipokines recently discovered to play a role in metabolic dysfunctions. This study aimed to evaluate some FNDCs (FNDC5, 4, 3A and B) as potential plasma and adipose tissue indicators of NEB in cattle. We measured plasma FNDC concentrations and adipose tissue FNDC gene expression during the peripartum period, 4 weeks before the estimated calving day (4WAP), one (1WPP) and 16 (16WPP) weeks postpartum in two groups of dairy cows with low NEB (LNEB, n = 8) and high NEB (HNEB, n = 13) at 1WPP. Using specific bovine ELISAs, only plasma FNDC5 concentrations varied during the peripartum period in both LNEB and HNEB animals; concentrations were higher at 1WPP as compared to 4WAP and 16 WPP. FNDC5 plasma concentrations was negatively correlated with dry matter intake, live body weight, variation of empty body weight and glucose concentrations, and positively correlated with plasma non-esterified fatty acids and BHBA concentrations. Subcutaneous adipose tissue contained abundant FNDC5 mRNA and protein, as measured by RT-qPCR and immunoblotting, respectively. We also observed that FNDC5 mRNA abundance in subcutaneous adipose tissue was higher at 1 WPP as compared to 4WAP and 16WPP in HNEB cows and higher at 1 WPP as compared to 4 WAP in LNEB cows, and was higher in HNEB than in LNEB animals during early lactation. Finally, we showed that recombinant human irisin (a fragmented product of FNDC5) increased the release of glycerol and abundance of mRNA encoding adipose triglyceride lipase and hormone-sensitive-lipase in bovine and human adipose tissue explants. In conclusion, FNDC5 is expressed in bovine adipose tissue and may be involved in lipid mobilization and regulation of NEB in cattle.

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Fndc4, a highly identical ortholog of Irisin binds and activates a novel orphan receptor G-protein coupled receptor

Cited by 2 publications

References 0 publications

Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer

Expression Analysis of Fibronectin Type III Domain-Containing (FNDC) Genes in Inflammatory Bowel Disease and Colorectal Cancer

Impact of fibronectin type III domain-containing family in the changes in metabolic and hormonal profiles during peripartum period in dairy cows

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