scholarly journals GLP-1 Induces the Expression of FNDC5 Derivatives That Execute Lipolytic Actions

2021 ◽  
Vol 9 ◽  
Author(s):  
Hui Li ◽  
William Donelan ◽  
Fang Wang ◽  
Peilan Zhang ◽  
Lijun Yang ◽  
...  
Keyword(s):  
Underlying Mechanism ◽  
The Body ◽  
Obese Mouse ◽  
Rat Tissues ◽  
Β Cells ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Diabetes And Obesity ◽  
Fibronectin Type

Multiple GLP-1-derived therapeutics are clinically used to treat type 2 diabetes and obesity. However, the underlying mechanism of how these drugs regulate the body weight of obese patients remains incompletely understood. Here, we report that the lipolysis effects of GLP-1 on β cells can depend on its induced expression of fibronectin type III domain containing 5 (FNDC5). The transmembrane FNDC5 is a precursor of the recently identified hormone irisin that possesses a range of bioactivities, including anti-obesity and anti-diabetes. We revealed that GLP-1 upregulates the expression and secretion of FNDC5 in β cells, while GLP-1 itself fails to activate the lipolysis genes in FNDC5-knockout β cells. In addition, liraglutide, a clinically used GLP-1 receptor agonist, induced the expression of FNDC5 in mouse pancreas and brain tissues and increased the serum level of secreted FNDC5. Furthermore, we observed the expression of the well-known membrane-associated FNDC5 and a novel, secretable FNDC5 (sFNDC5) isoform in β cells and multiple rat tissues. Recombinant sFNDC5 stimulated lipolysis of wild type and FNDC5-knockout β cells. This new isoform further induced lipolysis and browning of adipocytes, and similar to irisin, executed potent anti-obesity activities in an obese mouse model. Overall, our studies provided new mechanistic insights into GLP-1’s anti-obesity actions in which GLP-1 induces the secretion of FNDC5 derivatives from its responsive organs that then mediate its anti-obesity activities.

scholarly journals Administration of Bifidobacterium breve Improves the Brain Function of Aβ1-42-Treated Mice via the Modulation of the Gut Microbiome

Nutrients ◽  
2021 ◽  
Vol 13 (5) ◽  
pp. 1602
Author(s):  
Guangsu Zhu ◽  
Jianxin Zhao ◽  
Hao Zhang ◽  
Wei Chen ◽  
Gang Wang
Keyword(s):  
Gut Microbiome ◽  
Dietary Intervention ◽  
Neuroprotective Effects ◽  
Bifidobacterium Breve ◽  
Beneficial Effects ◽  
Behavioral Abnormalities ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
The Brain ◽  
Fibronectin Type

Psychobiotics are used to treat neurological disorders, including mild cognitive impairment (MCI) and Alzheimer’s disease (AD). However, the mechanisms underlying their neuroprotective effects remain unclear. Herein, we report that the administration of bifidobacteria in an AD mouse model improved behavioral abnormalities and modulated gut dysbiosis. Bifidobacterium breve CCFM1025 and WX treatment significantly improved synaptic plasticity and increased the concentrations of brain-derived neurotrophic factor (BDNF), fibronectin type III domain-containing protein 5 (FNDC5), and postsynaptic density protein 95 (PSD-95). Furthermore, the microbiome and metabolomic profiles of mice indicate that specific bacterial taxa and their metabolites correlate with AD-associated behaviors, suggesting that the gut–brain axis contributes to the pathophysiology of AD. Overall, these findings reveal that B. breve CCFM1025 and WX have beneficial effects on cognition via the modulation of the gut microbiome, and thus represent a novel probiotic dietary intervention for delaying the progression of AD.

scholarly journals A targeted adenovirus vector displaying a human fibronectin type III domain-based monobody in a fiber protein

Biomaterials ◽  
2013 ◽  
Vol 34 (16) ◽  
pp. 4191-4201 ◽  
Author(s):  
Hayato Matsui ◽  
Fuminori Sakurai ◽  
Kazufumi Katayama ◽  
Yasuhiro Abe ◽  
Mitsuhiro Machitani ◽  
...  
Keyword(s):  
Adenovirus Vector ◽  
Type Iii ◽  
Fiber Protein ◽  
Fibronectin Type Iii ◽  
Human Fibronectin ◽  
Fibronectin Type Iii Domain ◽  
Fibronectin Type

scholarly journals Structural Studies of an Immunoglobulin-Fibronectin Type III Domain Tandem from Titin

2011 ◽  
Vol 100 (3) ◽  
pp. 604a
Author(s):  
Andras Czajlik ◽  
Gary Thompson ◽  
Ghulam N. Khan ◽  
Arnout Kalverde ◽  
Steve W. Homans ◽  
...  
Keyword(s):  
Structural Studies ◽  
Type Iii ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Fibronectin Type

scholarly journals Interaction of CREB and PGC-1α Induces Fibronectin Type III Domain-Containing Protein 5 Expression in C2C12 Myotubes

2018 ◽  
Vol 50 (4) ◽  
pp. 1574-1584 ◽  
Author(s):  
Xiu-ying Yang ◽  
Margaret C.L. Tse ◽  
Xiang Hu ◽  
Wei-hua Jia ◽  
Guan-hua Du ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Molecular Mechanisms ◽  
Metabolic Effects ◽  
Hek293 Cells ◽  
Metabolic Phenotype ◽  
C2c12 Myotubes ◽  
Type Iii ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Fibronectin Type

Background/Aims: Fibronectin type III domain-containing protein 5 (FNDC5), also known as irisin, is a myokine secreted from muscle in response to exercise. However, the molecular mechanisms that regulate FNDC5 expression and the functional significance of irisn in skeletal muscle remain unknown. In this study, we explored the potential pathways that induce FNDC5 expression and delineated the metabolic effects of irisin on skeletal muscle. Methods: C2C12 myotubes were treated with drugs at various concentrations and durations. The expression and activation of genes were measured by real-time polymerase chain reaction (qRT-PCR) and Western blotting. Oxidative phosphorylation was quantified by measuring the oxygen consumption rate (OCR). Results: We found that the exercise-mimicking treatment (cAMP, forskolin and isoproterenol) increased Fndc5 expression in C2C12 myotubes. CREB over-expressed C2C12 myotubes displayed higher Fndc5 expression. CREB over-expression also promoted peroxisome proliferator-activated receptor gamma coactivator 1α (PGC-1α) expression. PGC-1α-induced Fndc5 expression was blocked when the dominant negative form of CREB (S133A) was present. PGC-1α mutation (S570A) also decreased Fndc5 expression. Immunoprecipitation showed that overexpressed PGC-1α complexed with CREB in HEK293 cells. C2C12 myotubes treated with forskolin also increased endogenous CREB and PGC-1α binding. Functionally, irisin treatment increased mitochondrial respiration, enhanced ATP production, promoted fatty acid oxidation but decreased glycolysis in myotubes. Conclusion: Our observation indicates that cAMP-mediated PGC-1α/CREB interaction triggers Fndc5 expression, which acts as an autocrine/paracrine to shape the metabolic phenotype of myotubes.

scholarly journals Mertk Interacts with Tim-4 to Enhance Tim-4-Mediated Efferocytosis

Cells ◽  
2020 ◽  
Vol 9 (7) ◽  
pp. 1625 ◽  
Author(s):  
Byeongjin Moon ◽  
Juyeon Lee ◽  
Sang-Ah Lee ◽  
Chanhyuk Min ◽  
Hyunji Moon ◽  
...  
Keyword(s):  
Cell Surface ◽  
Molecular Mechanism ◽  
Soluble Form ◽  
Physical Interaction ◽  
Apoptotic Cells ◽  
Type Iii ◽  
Biochemical Interaction ◽  
Fibronectin Type Iii ◽  
Fibronectin Type Iii Domain ◽  
Fibronectin Type

Apoptotic cells expressing phosphatidylserine (PS) on their cell surface are directly or indirectly recognized by phagocytes through PS-binding proteins. The PS-binding protein Tim-4 secures apoptotic cells to phagocytes to facilitate the engulfment of apoptotic cells. However, the molecular mechanism by which Tim-4 transduces signals to phagocytes during Tim-4-mediated efferocytosis is incompletely understood. Here, we report that Tim-4 collaborates with Mertk during efferocytosis through a biochemical interaction with Mertk. Proximal localization between the two proteins in phagocytes was observed by immunofluorescence and proximal ligation assays. Physical association between Tim-4 and Mertk, which was mediated by an interaction between the IgV domain of Tim-4 and the fibronectin type-III domain of Mertk, was also detected with immunoprecipitation. Furthermore, the effect of Mertk on Tim-4-mediated efferocytosis was abolished by GST-MertkFnIII, a soluble form of the fibronectin type-III domain of Mertk that disrupts the interaction between Tim-4 and Mertk. Taken together, the results from our study suggest that a physical interaction between Tim-4 and Mertk is necessary for Mertk to enhance efferocytosis mediated by Tim-4.

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

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Tilo Wuensch ◽  
Jonas Wizenty ◽  
Janina Quint ◽  
Wolfgang Spitz ◽  
Madeleen Bosma ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Factor ◽  
Type Iii ◽  
Fibronectin Type Iii ◽  
Inflammatory Bowel ◽  
Fibronectin Type Iii Domain ◽  
Fibronectin Type

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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