22
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: not found

      The metabolic effects of GDF15 are mediated by the orphan receptor GFRAL

      Read this article at

      ScienceOpenPublisherPubMed
      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

          GDF15 has potent anti-obesity effects, but its receptor was previously unknown. GFRAL has now been identified as the receptor for GDF15, and it mediates the effects of GDF15 via central actions in the hindbrain.

          Related collections

          Most cited references15

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

          Tumor-induced anorexia and weight loss are mediated by the TGF-beta superfamily cytokine MIC-1.

          Anorexia and weight loss are part of the wasting syndrome of late-stage cancer, are a major cause of morbidity and mortality in cancer, and are thought to be cytokine mediated. Macrophage inhibitory cytokine-1 (MIC-1) is produced by many cancers. Examination of sera from individuals with advanced prostate cancer showed a direct relationship between MIC-1 abundance and cancer-associated weight loss. In mice with xenografted prostate tumors, elevated MIC-1 levels were also associated with marked weight, fat and lean tissue loss that was mediated by decreased food intake and was reversed by administration of antibody to MIC-1. Additionally, normal mice given systemic MIC-1 and transgenic mice overexpressing MIC-1 showed hypophagia and reduced body weight. MIC-1 mediates its effects by central mechanisms that implicate the hypothalamic transforming growth factor-beta receptor II, extracellular signal-regulated kinases 1 and 2, signal transducer and activator of transcription-3, neuropeptide Y and pro-opiomelanocortin. Thus, MIC-1 is a newly defined central regulator of appetite and a potential target for the treatment of both cancer anorexia and weight loss, as well as of obesity.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: found
            Is Open Access

            GDF-15 as a Target and Biomarker for Diabetes and Cardiovascular Diseases: A Translational Prospective

            Growth differentiation factor-15 (GDF-15) is a stress responsive cytokine. It is highly expressed in cardiomyocytes, adipocytes, macrophages, endothelial cells, and vascular smooth muscle cells in normal and pathological condition. GDF-15 increases during tissue injury and inflammatory states and is associated with cardiometabolic risk. Increased GDF-15 levels are associated with cardiovascular diseases such as hypertrophy, heart failure, atherosclerosis, endothelial dysfunction, obesity, insulin resistance, diabetes, and chronic kidney diseases in diabetes. Increased GDF-15 level is linked with the progression and prognosis of the disease condition. Age, smoking, and environmental factors are other risk factors that may increase GDF-15 level. Most of the scientific studies reported that GDF-15 plays a protective role in different tissues. However, few reports show that the deficiency of GDF-15 is beneficial against vascular injury and inflammation. GDF-15 protects heart, adipose tissue, and endothelial cells by inhibiting JNK (c-Jun N-terminal kinase), Bad (Bcl-2-associated death promoter), and EGFR (epidermal growth factor receptor) and activating Smad, eNOS, PI3K, and AKT signaling pathways. The present review describes the different animal and clinical studies and patent updates of GDF-15 in diabetes and cardiovascular diseases. It is a challenge for the scientific community to use GDF-15 information for patient monitoring, clinical decision-making, and replacement of current treatment strategies for diabetic and cardiovascular diseases.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Promiscuity and specificity in BMP receptor activation.

              Bone Morphogenetic Proteins (BMPs), together with Transforming Growth Factor (TGF)-β and Activins/Inhibins constitute the TGF-β superfamily of ligands. This superfamily is formed by more than 30 structurally related secreted proteins. Since TGF-β members act as morphogens, either a strict relation between a particular ligand to a distinct cellular receptor and/or temporospatial expression patterns of ligands and receptors is expected. Instead, only a limited number of receptors exist implicating promiscuous interactions of ligands and receptors. Furthermore, in complex tissues a multitude of different ligands can be found, which signal via overlapping subsets of receptors. This raises the intriguing question how concerted interactions of different ligands and receptors generate highly specific cellular signals, which are required during development and tissue homeostasis. Copyright © 2012 Federation of European Biochemical Societies. Published by Elsevier B.V. All rights reserved.
                Bookmark

                Author and article information

                Journal
                Nature Medicine
                Nat Med
                Springer Nature
                1078-8956
                1546-170X
                August 28 2017
                August 28 2017
                :
                :
                Article
                10.1038/nm.4393
                28846098
                ea2f15a8-97ea-4121-8f42-40d87fd02c42
                © 2017
                History

                Comments

                Comment on this article