ID 109634
Author
Iwata, Takeo Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School KAKEN Search Researchers
Taniguchi, Hisaaki Division of Disease Proteomics, Institute for Enzyme Research, The University of Tokushima Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Kuwajima, Masamichi Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School|Taijukai-Kaisei General Hospital
Taniguchi, Takako Division of Disease Proteomics, Institute for Enzyme Research, The University of Tokushima KAKEN Search Researchers
Okuda, Yuko Division of Disease Proteomics, Institute for Enzyme Research, The University of Tokushima
Sukeno, Akiko Department of Clinical Biology and Medicine, Institute of Health Biosciences, The University of Tokushima Graduate School
Ishimoto, Kyoko Department of Orthodontics and Dentofacial Orthopedics, Institute of Health Biosciences, The University of Tokushima Graduate School KAKEN Search Researchers
Mizusawa, Noriko Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Yoshimoto, Katsuhiko Department of Medical Pharmacology, Institute of Health Biosciences, The University of Tokushima Graduate School Tokushima University Educator and Researcher Directory KAKEN Search Researchers
Content Type
Journal Article
Description
Adipose tissue is a critical exchange center for complex energy transactions involving triacylglycerol storage and release. It also has an active endocrine role, releasing various adipose-derived cytokines (adipokines) that participate in complex pathways to maintain metabolic and vascular health. Here, we found D-dopachrome tautomerase (DDT) as an adipokine secreted from human adipocytes by a proteomic approach. DDT mRNA levels in human adipocytes were negatively correlated with obesity-related clinical parameters such as BMI, and visceral and subcutaneous fat areas. Experiments using SGBS cells, a human preadipocyte cell line, revealed that DDT mRNA levels were increased in an adipocyte differentiationdependent manner and DDT was secreted from adipocytes. In DDT knockdown adipocytes differentiated from SGBS cells that were infected with the adenovirus expressing shRNA against the DDT gene, mRNA levels of genes involved in both lipolysis and lipogenesis were slightly but significantly increased. Furthermore, we investigated AMP-activated protein kinase (AMPK) signaling, which phosphorylates and inactivates enzymes involved in lipid metabolism, including hormonesensitive lipase (HSL) and acetyl-CoA carboxylase (ACC), in DDT knockdown adipocytes. The AMPK phosphorylation of HSL Ser-565 and ACC Ser-79 was inhibited in DDT knockdown cells and recovered in the cells treated with recombinant DDT (rDDT), suggesting that down-regulated DDT in adipocytes brings about a state of active lipid metabolism. Furthermore, administration of rDDT in db/db mice improved glucose intolerance and decreased serum free fatty acids levels. In the adipose tissue from rDDT-treated db/db mice, not only increased levels of HSL phosphorylated by AMPK, but also decreased levels of HSL phosphorylated by protein kinase A (PKA), which phosphorylates HSL to promote its activity, were observed.
These results suggested that DDT acts on adipocytes to regulate lipid metabolism through AMPK and/or PKA pathway(s) and improves glucose intolerance caused by obesity.
Journal Title
PLOS ONE
ISSN
19326203
Volume
7
Issue
3
Start Page
1
End Page
13
Sort Key
1
Published Date
2012-03
Remark
Copyright: 2012 Iwata 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.
EDB ID
Published Source
PLoS ONE 7(3): e33402. doi:10.1371/journal.pone.0033402
URL ( Publisher's Version )
FullText File
language
eng
TextVersion
Publisher
departments
Oral Sciences
Institute of Advanced Medical Sciences
University Hospital