96
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Effects and Molecular Mechanism of GST-Irisin on Lipolysis and Autocrine Function in 3T3-L1 Adipocytes

      research-article

      Read this article at

      Bookmark
          There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

          Abstract

          Irisin, which was recently identified as a myokine and an adipokine, transforms white adipose tissue to brown adipose tissue and has increasingly caught the attention of the medical and scientific community. However, the signaling pathway of irisin and the molecular mechanisms responsible for the lipolysis effect remain unclear. In this study, we established an efficient system for the expression and purification of GST-irisin in Escherichia coli. The biological activity of GST-irisin was verified using the cell counting kit-8 assay and by detecting the mRNA expression of uncoupling protein 1. Our data showed that GST-irisin regulates mRNA levels of lipolysis-related genes such as adipose triglyceride lipase and hormone-sensitive lipase and proteins such as the fatty acid-binding protein 4, leading to increased secretion of glycerol and decreased lipid accumulation in 3T3-L1 adipocytes. In addition, exogenous GST-irisin can increase its autocrine function in vitro by regulating the expression of fibronectin type III domain-containing protein 5. GST-irisin could regulate glucose uptake in 3T3-L1 adipocytes. Hence, we believe that recombinant GST-irisin could promote lipolysis and its secretion in vitro and can potentially prevent obesity and related metabolic diseases.

          Related collections

          Most cited references29

          • Record: found
          • Abstract: found
          • Article: not found

          Irisin stimulates browning of white adipocytes through mitogen-activated protein kinase p38 MAP kinase and ERK MAP kinase signaling.

          The number and activity of brown adipocytes are linked to the ability of mammals to resist body fat accumulation. In some conditions, certain white adipose tissue (WAT) depots are readily convertible to a ''brown-like'' state, which is associated with weight loss. Irisin, a newly identified hormone, is secreted by skeletal muscles into circulation and promotes WAT "browning" with unknown mechanisms. In the current study, we demonstrated in mice that recombinant irisin decreased the body weight and improved glucose homeostasis. We further showed that irisin upregulated uncoupling protein-1 (UCP-1; a regulator of thermogenic capability of brown fat) expression. This effect was possibly mediated by irisin-induced phosphorylation of the p38 mitogen-activated protein kinase (p38 MAPK) and extracellular signal-related kinase (ERK) signaling pathways. Inhibition of the p38 MAPK by SB203580 and ERK by U0126 abolished the upregulatory effect of irisin on UCP-1. In addition, irisin also promoted the expression of betatrophin, another newly identified hormone that promotes pancreatic β-cell proliferation and improves glucose tolerance. In summary, our data suggest that irisin can potentially prevent obesity and associated type 2 diabetes by stimulating expression of WAT browning-specific genes via the p38 MAPK and ERK pathways.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            FNDC5/Irisin Is Not Only a Myokine but Also an Adipokine

            Exercise provides clear beneficial effects for the prevention of numerous diseases. However, many of the molecular events responsible for the curative and protective role of exercise remain elusive. The recent discovery of FNDC5/irisin protein that is liberated by muscle tissue in response to exercise might be an important finding with regard to this unsolved mechanism. The most striking aspect of this myokine is its alleged capacity to drive brown-fat development of white fat and thermogenesis. However, the nature and secretion form of this new protein is controversial. The present study reveals that rat skeletal muscle secretes a 25 kDa form of FNDC5, while the 12 kDa/irisin theoretical peptide was not detected. More importantly, this study is the first to reveal that white adipose tissue (WAT) also secretes FNDC5; hence, it may also behave as an adipokine. Our data using rat adipose tissue explants secretomes proves that visceral adipose tissue (VAT), and especially subcutaneous adipose tissue (SAT), express and secrete FNDC5. We also show that short-term periods of endurance exercise training induced FNDC5 secretion by SAT and VAT. Moreover, we observed that WAT significantly reduced FNDC5 secretion in fasting animals. Interestingly, WAT of obese animals over-secreted this hormone, which might suggest a type of resistance. Because 72% of circulating FNDC5/irisin was previously attributed to muscle secretion, our findings suggest a muscle-adipose tissue crosstalk through a regulatory feedback mechanism.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              The multigene family of fatty acid-binding proteins (FABPs): function, structure and polymorphism.

              Fatty acid-binding proteins (FABPs) are members of the superfamily of lipid-binding proteins (LBP). So far 9 different FABPs, with tissue-specific distribution, have been identified: L (liver), I (intestinal), H (muscle and heart), A (adipocyte), E (epidermal), Il (ileal), B (brain), M (myelin) and T (testis). The primary role of all the FABP family members is regulation of fatty acid uptake and intracellular transport. The structure of all FABPs is similar - the basic motif characterizing these proteins is beta-barrel, and a single ligand (e.g. a fatty acid, cholesterol, or retinoid) is bound in its internal water-filled cavity. Despite the wide variance in the protein sequence, the gene structure is identical. The FABP genes consist of 4 exons and 3 introns and a few of them are located in the same chromosomal region. For example, A-FABP, E-FABP and M-FABP create a gene cluster. Because of their physiological properties some FABP genes were tested in order to identify mutations altering lipid metabolism. Furthermore, the porcine A-FABP and H-FABP were studied as candidate genes with major effect on fatness traits.
                Bookmark

                Author and article information

                Contributors
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                22 January 2016
                2016
                : 11
                : 1
                : e0147480
                Affiliations
                [1 ]Key Laboratory for Molecular Enzymology and Engineering of the Ministry of Education, Jilin University, 2699 Qianjin Street, Changchun, 130012, China
                [2 ]School of Life Sciences, Jilin University, Changchun, 130012, China
                [3 ]National Engineering Laboratory for AIDS Vaccine, Jilin University, Changchun, 130012, China
                [4 ]Department of Endocrinology, the Second Hospital of Jilin University, Changchun, 130041, China
                GDC, GERMANY
                Author notes

                Competing Interests: The authors have declared that no competing interests exist.

                Conceived and designed the experiments: SSG YL YXC. Performed the experiments: SSG FML HML. Analyzed the data: SSG YBH YL YXC. Contributed reagents/materials/analysis tools: SSG YBH. Wrote the paper: SSG YL YXC.

                Article
                PONE-D-15-47732
                10.1371/journal.pone.0147480
                4723061
                26799325
                d20e8496-9737-4dd4-9fe0-6825ba781445
                © 2016 Gao et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 5 November 2015
                : 5 January 2016
                Page count
                Figures: 5, Tables: 0, Pages: 15
                Funding
                This work was supported by the National Natural Science Foundation of China (no. 81373445, YXC, no. 21442001, YBH, no. 30971398, YL, and no. 81170746, YL), the Natural Science Foundation of Jilin Province (no. 20150101189JC, YXC and no. 20140101042JC, YBH), Norman Bethune Program of Jilin University (no. 2012214, YL), and Science and Technology Development Program of Jilin Province (no. 20140101183JC, YL and no. 20150519013JH, YL).
                Categories
                Research Article
                Biology and Life Sciences
                Cell Biology
                Cellular Types
                Animal Cells
                Connective Tissue Cells
                Adipocytes
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Connective Tissue Cells
                Adipocytes
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Connective Tissue Cells
                Adipocytes
                Physical Sciences
                Chemistry
                Chemical Reactions
                Hydrolysis
                Lipolysis
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Carbohydrate Metabolism
                Glucose Metabolism
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Adipose Tissue
                Brown Adipose Tissue
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Adipose Tissue
                Brown Adipose Tissue
                Physical sciences
                Chemistry
                Polymer chemistry
                Monomers (Chemistry)
                Glycerol
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Biology and Life Sciences
                Biochemistry
                Lipids
                Biology and life sciences
                Cell biology
                Signal transduction
                Cell signaling
                Signaling cascades
                MAPK signaling cascades
                Custom metadata
                All relevant data are within the paper and its Supporting Information files.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article