7
views
0
recommends
+1 Recommend
0 collections
    0
    shares
      • Record: found
      • Abstract: found
      • Article: found
      Is Open Access

      Photoperiodic changes in adiposity increase sensitivity of female Siberian hamsters to systemic VGF derived peptide TLQP-21

      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

          TLQP-21, a peptide encoded by the highly conserved vgf gene, is expressed in neuroendocrine cells and has been the most prominent VGF-derived peptide studied in relation to control of energy balance. The recent discovery that TLQP-21 is the natural agonist for the complement 3a receptor 1 (C3aR1) has revived interest in this peptide as a potential drug target for obesity. We have investigated its function in Siberian hamsters ( Phodopus sungorus), a rodent that displays natural seasonal changes in body weight and adiposity as an adaptation to survive winter. We have previously shown that intracerebroventricular administration of TLQP-21 reduced food intake and body weight in hamsters in their long-day fat state. The aim of our current study was to determine the systemic actions of TLQP-21 on food intake, energy expenditure and body weight, and to establish whether adiposity affected these responses. Peripheral infusion of TLQP-21 (1mg/kg/day for 7 days) in lean hamsters exposed to short photoperiods (SP) reduced cumulative food intake in the home cage (p<0.05), and intake when measured in metabolic cages (P<0.01). Energy expenditure was significantly increased (p<0.001) by TLQP-21 infusion, this was associated with a significant increase in uncoupling protein 1 mRNA in brown adipose tissue (BAT) (p<0.05), and body weight was significantly reduced (p<0.05). These effects of systemic TLQP-21 treatment were not observed in hamsters exposed to long photoperiod (LP) with a fat phenotype. C3aR1 mRNA and protein were abundantly expressed in the hypothalamus, brown and white adipose tissue in hamsters, but changes in expression cannot explain the differential response to TLQP-21 in lean and fat hamsters.

          Related collections

          Most cited references35

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

          Toward an Understanding of How Immune Cells Control Brown and Beige Adipobiology.

          Immune cells were recently found to have an unexpected involvement in controlling the thermogenic activity of brown and beige adipose tissue. Here, we review how macrophages, eosinophils, type 2 innate lymphoid cells, and T lymphocytes are linked to this process. In particular, the recruitment of alternatively activated macrophages and eosinophils is associated with brown fat activation and white fat browning. Conversely, pro-inflammatory immune cell recruitment represses the thermogenic activity of brown and beige adipose tissues via cytokines that inhibit noradrenergic signaling. Macrophages also influence the noradrenergic tone by degrading norepinephrine locally and by inhibiting sympathetic innervation over time.
            Bookmark
            • Record: found
            • Abstract: found
            • Article: not found

            TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity.

            The vgf gene has been identified as an energy homeostasis regulator. Vgf encodes a 617-aa precursor protein that is processed to yield an incompletely characterized panel of neuropeptides. Until now, it was an unproved assumption that VGF-derived peptides could regulate metabolism. Here, a VGF peptide designated TLQP-21 was identified in rat brain extracts by means of immunoprecipitation, microcapillary liquid chromatography-tandem MS, and database searching algorithms. Chronic intracerebroventricular (i.c.v.) injection of TLQP-21 (15 mug/day for 14 days) increased resting energy expenditure (EE) and rectal temperature in mice. These effects were paralleled by increased epinephrine and up-regulation of brown adipose tissue beta2-AR (beta2 adrenergic receptor) and white adipose tissue (WAT) PPAR-delta (peroxisome proliferator-activated receptor delta), beta3-AR, and UCP1 (uncoupling protein 1) mRNAs and were independent of locomotor activity and thyroid hormones. Hypothalamic gene expression of orexigenic and anorexigenic neuropeptides was unchanged. Furthermore, in mice that were fed a high-fat diet for 14 days, TLQP-21 prevented the increase in body and WAT weight as well as hormonal changes that are associated with a high-fat regimen. Biochemical and molecular analyses suggest that TLQP-21 exerts its effects by stimulating autonomic activation of adrenal medulla and adipose tissues. In conclusion, we present here the identification in the CNS of a previously uncharacterized VGF-derived peptide and prove that its chronic i.c.v. infusion effected an increase in EE and limited the early phase of diet-induced obesity.
              Bookmark
              • Record: found
              • Abstract: found
              • Article: not found

              Identification of the C3a receptor (C3AR1) as the target of the VGF-derived peptide TLQP-21 in rodent cells.

              TLQP-21, a peptide derived from VGF (non-acronymic) by proteolytic processing, has been shown to modulate energy metabolism, differentiation, and cellular response to stress. Although extensively investigated, the receptor for this endogenous peptide has not previously been described. This study describes the use of a series of studies that show G protein-coupled receptor-mediated biological activity of TLQP-21 signaling in CHO-K1 cells. Unbiased genome-wide sequencing of the transcriptome from responsive CHO-K1 cells identified a prioritized list of possible G protein-coupled receptors bringing about this activity. Further experiments using a series of defined receptor antagonists and siRNAs led to the identification of complement C3a receptor-1 (C3AR1) as a target for TLQP-21 in rodents. We have not been able to demonstrate so far that this finding is translatable to the human receptor. Our results are in line with a large number of physiological observations in rodent models of food intake and metabolic control, where TLQP-21 shows activity. In addition, the sensitivity of TLQP-21 signaling to pertussis toxin is consistent with the known signaling pathway of C3AR1. The binding of TLQP-21 to C3AR1 not only has effects on signaling but also modulates cellular functions, as TLQP-21 was shown to have a role in directing migration of mouse RAW264.7 cells.
                Bookmark

                Author and article information

                Contributors
                Role: Data curationRole: InvestigationRole: Writing – review & editing
                Role: Data curationRole: InvestigationRole: MethodologyRole: Writing – original draft
                Role: Data curationRole: Formal analysisRole: Methodology
                Role: Methodology
                Role: Data curationRole: Investigation
                Role: Data curationRole: Investigation
                Role: Data curationRole: Formal analysisRole: Investigation
                Role: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: SupervisionRole: Writing – review & editing
                Role: Funding acquisitionRole: MethodologyRole: Project administrationRole: SupervisionRole: Writing – original draftRole: Writing – review & editing
                Role: Editor
                Journal
                PLoS One
                PLoS ONE
                plos
                plosone
                PLoS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                29 August 2019
                2019
                : 14
                : 8
                : e0221517
                Affiliations
                [1 ] NEF-Laboratory, Dept. of Biomedical Sciences, University of Cagliari, Cagliari, Italy
                [2 ] School of Life Sciences, University of Nottingham Medical School, Nottingham, United Kingdom
                [3 ] Institute of Metabolic Sciences and MRC-Metabolic Diseases Unit, University of Cambridge, Cambridge, United Kingdom
                [4 ] School of Biosciences, University of Nottingham Sutton Bonington Campus, Nottingham, United Kingdom
                [5 ] Institute for Biodiversity, Animal Health and Comparative Medicine, University of Glasgow, Glasgow, United Kingdom
                University of Minnesota, UNITED STATES
                Author notes

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

                Author information
                http://orcid.org/0000-0003-2644-9685
                http://orcid.org/0000-0003-4401-284X
                Article
                PONE-D-19-03738
                10.1371/journal.pone.0221517
                6715173
                31465472
                0c2118ac-2a13-4c81-b0d1-2d73bac16919
                © 2019 Lisci 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
                : 7 February 2019
                : 8 August 2019
                Page count
                Figures: 5, Tables: 1, Pages: 14
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/501100009873, Regione Autonoma della Sardegna;
                Award ID: CRP-26206
                Award Recipient :
                This work was supported by the British Society of Neuroendocrinology (PHJ; https://www.neuroendo.org.uk/)and Regione Sardegna (RAS) basic research funds CRP-26206 (GLF; https://www.researchitaly.it/en/home/). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Organisms
                Eukaryota
                Animals
                Vertebrates
                Amniotes
                Mammals
                Rodents
                Hamsters
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Adipose Tissue
                Brown Adipose Tissue
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Adipose Tissue
                Brown Adipose Tissue
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Biology and Life Sciences
                Biochemistry
                Bioenergetics
                Biology and Life Sciences
                Anatomy
                Brain
                Hypothalamus
                Medicine and Health Sciences
                Anatomy
                Brain
                Hypothalamus
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fats
                Biology and Life Sciences
                Molecular Biology
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Protein Expression
                Research and Analysis Methods
                Molecular Biology Techniques
                Molecular Biology Assays and Analysis Techniques
                Gene Expression and Vector Techniques
                Protein Expression
                Biology and Life Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Medicine and Health Sciences
                Physiology
                Physiological Parameters
                Body Weight
                Obesity
                Custom metadata
                All relevant data are within the paper.

                Uncategorized
                Uncategorized

                Comments

                Comment on this article