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A Disintegrin and Metalloproteinase with Thrombospondin Motifs 18 Deficiency Leads to Visceral Adiposity and Associated Metabolic Syndrome in Mice.
- Source :
-
The American journal of pathology [Am J Pathol] 2018 Feb; Vol. 188 (2), pp. 461-473. Date of Electronic Publication: 2017 Nov 21. - Publication Year :
- 2018
-
Abstract
- Visceral adiposity is of greater risk than obesity in s.c. adipose tissue for diabetes and cardiovascular disease. Its pathogenesis remains unclear, but it is associated with extracellular matrix (ECM) remodeling. A disintegrin and metalloproteinase with thrombospondin motifs (ADAMTSs) are a family of secreted zinc-dependent metalloproteinases that play crucial roles in development and various diseases because of their ECM remodeling activity. ADAMTS18 is an orphan ADAMTS whose function and substrate remain unclear. Herein, we showed that Adamts18 mRNA was abundantly expressed in visceral (gonadal) white adipose tissue (vWAT) during the early stage of development after birth. Adamts18 knockout (KO) mice showed increased body fat percentage and larger adipocyte size in vWAT relative to wild-type littermates. These findings may be partly attributed to ECM remodeling, especially increased expression of laminin 1 and adipokine thrombospondin 1 in vWAT. Attenuated extracellular signal-regulated kinase 1 and 2 activity, along with increased expression of adipocyte-specific transcription factors peroxisome proliferator-activated receptor-γ, CCAAT/enhancer binding protein β, and marker gene Fabp4, was detected in vWAT of Adamts18 KO mice. Furthermore, Adamts18 KO mice showed early metabolic syndrome, including hyperlipidemia, blood glucose metabolic disorder, and hypertension. ADAMTS18 deficiency promotes atherosclerosis in apolipoprotein E-deficient mice. These results indicate a novel function of ADAMTS18 in vWAT development and associated metabolic disorders.<br /> (Copyright © 2018 American Society for Investigative Pathology. Published by Elsevier Inc. All rights reserved.)
- Subjects :
- ADAMTS Proteins deficiency
ADAMTS Proteins genetics
Adipocytes pathology
Animals
Atherosclerosis metabolism
Atherosclerosis physiopathology
Cells, Cultured
Extracellular Matrix physiology
Gene Expression Regulation, Developmental physiology
Intra-Abdominal Fat pathology
Lipids blood
Male
Metabolic Syndrome pathology
Mice, Knockout
RNA, Messenger genetics
ADAMTS Proteins physiology
Adiposity physiology
Intra-Abdominal Fat metabolism
Metabolic Syndrome metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1525-2191
- Volume :
- 188
- Issue :
- 2
- Database :
- MEDLINE
- Journal :
- The American journal of pathology
- Publication Type :
- Academic Journal
- Accession number :
- 29169989
- Full Text :
- https://doi.org/10.1016/j.ajpath.2017.10.020