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- Title
Distinctive Features of Orbital Adipose Tissue (OAT) in Graves' Orbitopathy.
- Authors
Zhang, Lei; Evans, Anna; von Ruhland, Chris; Draman, Mohd Shazli; Edkins, Sarah; Vincent, Amy E.; Berlinguer-Palmini, Rolando; Rees, D. Aled; Haridas, Anjana S; Morris, Dan; Tee, Andrew R.; Ludgate, Marian; Turnbull, Doug M.; Karpe, Fredrik; Dayan, Colin M.
- Abstract
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.
- Subjects
ADIPOSE tissues; OATS; ESSENTIAL fatty acids; UNCOUPLING proteins; MITOCHONDRIA
- Publication
International Journal of Molecular Sciences, 2020, Vol 21, Issue 23, p9145
- ISSN
1661-6596
- Publication type
Article
- DOI
10.3390/ijms21239145