Cathepsin K in adipocyte differentiation and its potential role in the pathogenesis of obesity.
BACKGROUND
The alteration of protein expression in white adipose tissue (WAT) may contribute to the pathogenesis of obesity.


OBJECTIVE
The aim of the present study was to uncover proteins differentially expressed in the WAT of overweight/obese subjects and study the role of the identified proteins in adipocyte differentiation.


METHODS
Two-dimensional electrophoresis and matrix-assisted laser desorption ionization-time of flight-mass spectrometry were used to identify proteins differentially expressed in WAT between obese/overweight and control groups. Cathepsin K (CTSK), one of the proteins identified by the above methods, was highlighted to assess its effects on adipocyte differentiation through 3T3-L1 cell line.


RESULTS
Human visceral adipose tissue of overweight/obese subjects displayed a differential protein expression profile, compared with that of normal-weight controls. CTSK was up-regulated in the WAT of overweight/obese subjects, and it had a significant positive correlation with body mass index. In vitro study showed that CTSK expression and its enzyme activity gradually increased in the process of adipocyte differentiation. Moreover, E-64, an inhibitor of CTSK, could prevent adipocyte differentiation in a dose-dependent manner, which was characterized by the absence of triglyceride accumulation and glycerol contents.


CONCLUSIONS
CTSK, a cysteine protease involved in extracellular matrix remodeling, could be one of the determinants of adipocyte differentiation. CTSK may be involved in the pathogenesis of obesity by promoting adipocyte differentiation.
Xiao
Yin
Y
Shanghai Institute of Endocrinology and Metabolism, Shanghai Second Medical University, Rui-Jin Hospital, Shanghai 200025, People's Republic of China. xysq74@hotmail.com
Junfeng
Han
H
Tianhong
Luo
L
Lu
Wang
W
Shulin
Chen
C
Yu
Zhao
Z
Xiaohua
Li
L
Weixia
Jian
J
Sheng
Zheng
Z
Yanyun
Gu
G
Guo
Li
L
Min
Luo
L
D041721:3T3-L1 Cells; D017667:Adipocytes / Q000187:drug effects / Q000201:enzymology / Q000502:physiology*; D052436:Adipose Tissue, White / Q000378:metabolism; D000328:Adult; D000818:Animals; D015415:Biomarkers; D056657:Cathepsin K; D002403:Cathepsins / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D002454:Cell Differentiation / Q000187:drug effects / Q000502:physiology*; D015180:Electrophoresis, Gel, Two-Dimensional; D004791:Enzyme Inhibitors / Q000494:pharmacology; D005260:Female; D015870:Gene Expression; D006801:Humans; D008297:Male; D051379:Mice; D008875:Middle Aged; D009765:Obesity / Q000209:etiology* / Q000378:metabolism; D040901:Proteomics / Q000379:methods; D014018:Tissue Distribution
D015415:Biomarkers; D004791:Enzyme Inhibitors; D002403:Cathepsins; C534130:CTSK protein, human; D056657:Cathepsin K; C534132:Ctsk protein, mouse