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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. 188:461-473
- Publication Year :
- 2018
- Publisher :
- Elsevier BV, 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.
- Subjects :
- Male
0301 basic medicine
medicine.medical_specialty
Adipokine
Adipose tissue
White adipose tissue
Intra-Abdominal Fat
Biology
Pathology and Forensic Medicine
03 medical and health sciences
chemistry.chemical_compound
ADAMTS Proteins
0302 clinical medicine
Internal medicine
Enhancer binding
Adipocyte
Thrombospondin 1
Adipocytes
medicine
Animals
RNA, Messenger
Cells, Cultured
Adiposity
Metabolic Syndrome
Mice, Knockout
Thrombospondin
ADAMTS
Gene Expression Regulation, Developmental
Atherosclerosis
Lipids
Extracellular Matrix
030104 developmental biology
Endocrinology
chemistry
030217 neurology & neurosurgery
Subjects
Details
- ISSN :
- 00029440
- Volume :
- 188
- Database :
- OpenAIRE
- Journal :
- The American Journal of Pathology
- Accession number :
- edsair.doi.dedup.....ea96be746e7c5596e9a923e62af43833