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Cathepsin K in Adipocyte Differentiation and Its Potential Role in the Pathogenesis of Obesity

Shanghai Institute of Endocrine and Metabolism, Shanghai Second Medical University, Rui-Jin Hospital, Shanghai 200025, People’s Republic of China

Address all correspondence and requests for reprints to: Yin Xiao, Department of Endocrinology and Metabolism, Central Hospital of Jinan, Shandong 250013, People’s Republic of China. E-mail: xysq74{at}hotmail.com; or Han Junfeng, Shanghai Institute of Endocrine and Metabolism, Shanghai Second Medical University, Rui-Jin Hospital, 197 Rui-Jin Road II, Shanghai 200025, People’s Republic of China; or Luo Min, Shanghai Institute of Endocrine and Metabolism, Shanghai Second Medical University, Rui-Jin Hospital, 197 Rui-Jin Road II, Shanghai 200025, People’s Republic of China.

Context: 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.

Design and Setting: 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.

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