Next Article in Journal
Molecular Aspects of Sex Development in Mammals: New Insight for Practice
Previous Article in Journal
Leptin Mediated Pathways Stabilize Posttraumatic Insulin and Osteocalcin Patterns after Long Bone Fracture and Concomitant Traumatic Brain Injury and Thus Influence Fracture Healing in a Combined Murine Trauma Model
Open AccessArticle

Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy

1
School of Medicine, Cardiff University, Heath Park, Cardiff CF14 4XN, UK
2
Wellcome Centre for Mitochondrial Research, Translational and Clinical Research Institute, Faculty of Medical Sciences, Newcastle University, Newcastle NE2 4HH, UK
3
The Bio-Imaging Unit, Faculty of Medical Sciences, Newcastle University, Newcastle NE2 4HH, UK
4
Department of Ophthalmology, Cardiff & Vale University Health Board, Cardiff CF14 4XW, UK
5
Oxford Centre for Diabetes, Endocrinology and Metabolism, Radcliffe Department of Medicine, University of Oxford, Oxford OX3 7LE, UK
6
NIHR Oxford Biomedical Research Center, OUH Foundation Trust, Oxford OX4 2PG, UK
*
Author to whom correspondence should be addressed.
Int. J. Mol. Sci. 2020, 21(23), 9145; https://doi.org/10.3390/ijms21239145
Received: 30 October 2020 / Revised: 20 November 2020 / Accepted: 28 November 2020 / Published: 30 November 2020
(This article belongs to the Section Molecular Endocrinology and Metabolism)
Depot specific expansion of orbital-adipose-tissue (OAT) in Graves’ Orbitopathy (GO) is associated with lipid metabolism signaling defects. We hypothesize that the unique adipocyte biology of OAT facilitates its expansion in GO. A comprehensive comparison of OAT and white-adipose-tissue (WAT) was performed by light/electron-microscopy, lipidomic and transcriptional analysis using ex vivo WAT, healthy OAT (OAT-H) and OAT from GO (OAT-GO). OAT-H/OAT-GO have a single lipid-vacuole and low mitochondrial number. Lower lipolytic activity and smaller adipocytes of OAT-H/OAT-GO, accompanied by similar essential linoleic fatty acid (FA) and (low) FA synthesis to WAT, revealed a hyperplastic OAT expansion through external FA-uptake via abundant SLC27A6 (FA-transporter) expression. Mitochondrial dysfunction of OAT in GO was apparent, as evidenced by the increased mRNA expression of uncoupling protein 1 (UCP1) and mitofusin-2 (MFN2) in OAT-GO compared to OAT-H. Transcriptional profiles of OAT-H revealed high expression of Iroquois homeobox-family (IRX-3&5), and low expression in HOX-family/TBX5 (essential for WAT/BAT (brown-adipose-tissue)/BRITE (BRown-in-whITE) development). We demonstrated unique features of OAT not presented in either WAT or BAT/BRITE. This study reveals that the pathologically enhanced FA-uptake driven hyperplastic expansion of OAT in GO is associated with a depot specific mechanism (the SLC27A6 FA-transporter) and mitochondrial dysfunction. We uncovered that OAT functions as a distinctive fat depot, providing novel insights into adipocyte biology and the pathological development of OAT expansion in GO. View Full-Text
Keywords: Graves’ orbitopathy; orbital adipose tissue; WAT; BAT and BRITE; fatty acid uptake; hyperplasic adipocyte expansion Graves’ orbitopathy; orbital adipose tissue; WAT; BAT and BRITE; fatty acid uptake; hyperplasic adipocyte expansion
Show Figures

Figure 1

MDPI and ACS Style

Zhang, L.; Evans, A.; von Ruhland, C.; Draman, M.S.; Edkins, S.; Vincent, A.E.; Berlinguer-Palmini, R.; Rees, D.A.; Haridas, A.S; Morris, D.; Tee, A.R.; Ludgate, M.; Turnbull, D.M.; Karpe, F.; Dayan, C.M. Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy. Int. J. Mol. Sci. 2020, 21, 9145.

AMA Style

Zhang L, Evans A, von Ruhland C, Draman MS, Edkins S, Vincent AE, Berlinguer-Palmini R, Rees DA, Haridas AS, Morris D, Tee AR, Ludgate M, Turnbull DM, Karpe F, Dayan CM. Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy. International Journal of Molecular Sciences. 2020; 21(23):9145.

Chicago/Turabian Style

Zhang, Lei; Evans, Anna; von Ruhland, Chris; Draman, Mohd S.; Edkins, Sarah; Vincent, Amy E.; Berlinguer-Palmini, Rolando; Rees, D. A.; Haridas, Anjana S; Morris, Dan; Tee, Andrew R.; Ludgate, Marian; Turnbull, Doug M.; Karpe, Fredrik; Dayan, Colin M. 2020. "Distinctive Features of Orbital Adipose Tissue (OAT) in Graves’ Orbitopathy" Int. J. Mol. Sci. 21, no. 23: 9145.

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Search more from Scilit
 
Search
Back to TopTop