Letter abstract
Nature Cell Biology 9, 970 - 977 (2007)
Published online: 22 July 2007 | doi:10.1038/ncb1623
Cathepsin L activity controls adipogenesis and glucose tolerance
Min Yang1,2,11, Yaou Zhang3,11, Jiehong Pan3,11, Jiusong Sun1,11, Jian Liu1, Peter Libby1, Galina K. Sukhova1, Alessandro Doria4, Nobuhiko Katunuma5, Odile D. Peroni6, Michèle Guerre-Millo7,8,9,10, Barbara B. Kahn6, Karine Clement7,8,9,10 & Guo-Ping Shi1
Cysteine proteases play an important part in human pathobiology1. This report shows the participation of cathepsin L (CatL) in adipogenesis and glucose intolerance. In vitro studies demonstrate the role of CatL in the degradation of the matrix protein fibronectin, insulin receptor (IR) and insulin-like growth factor-1 receptor (IGF-1R), essential molecules for adipogenesis and glucose metabolism2, 3, 4, 5. CatL inhibition leads to the reduction of human and murine pre-adipocyte adipogenesis or lipid accumulation, protection of fibronectin from degradation, accumulation of IR and IGF-1R 
-subunits, and an increase in glucose uptake. CatL-deficient mice are lean and have reduced levels of serum glucose and insulin but increased levels of muscle IR -subunits, fibronectin and glucose transporter (Glut)-4, although food/water intake and energy expenditure of these mice are no less than their wild-type littermates. Importantly, the pharmacological inhibition of CatL also demonstrates reduced body weight gain and serum insulin levels, and increased glucose tolerance, probably due to increased levels of muscle IR -subunits, fibronectin and Glut-4 in both diet-induced obese mice and ob/ob mice. Increased levels of CatL in obese and diabetic patients suggest that this protease is a novel target for these metabolic disorders.
- Cardiovascular Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts 02115, USA
- Department of Rheumatology, Nanfang Hospital and Nanfang Medical University, Guangzhou 510515, China
- Department of Medicine, University of California, San Francisco, California 94143, USA
- Section on Genetics and Epidemiology, Joslin Diabetes Center and Harvard Medical School, Boston, Massachusetts 02215, USA
- Institute for Health Sciences, Tokushima Bunri University, Tokushima 770-8514, Japan
- Department of Medicine, Beth Israel-Deaconess Medical Center and Harvard Medical School, Boston, Massachusetts 02115, USA
- INSERM, U 872, Nutriomique Team 7, Paris, F-75006 France
- Université Pierre et Marie Curie-Paris 6, Centre de Recherche des Cordeliers, UMRS 872, Paris, F-75006 France
- Université Paris Descartes, UMRS 872, Paris, F-75006 France
- AP/HP, Nutrition Department, Pitié-Salpétrière Hospital, Paris, F-75013, France
- Authors contributed equally to this study.
Correspondence to: Guo-Ping Shi1 e-mail: gshi@rics.bwh.harvard.edu
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