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- Title
Cathepsin L activity controls adipogenesis and glucose tolerance.
- Authors
Min Yang; Yaou Zhang; Jiehong Pan; Jiusong Sun; Jian Liu; Libby, Peter; Sukhova, Galina K.; Doria, Alessandro; Katunuma, Nobuhiko; Peroni, Odile D.; Guerre-Millo, Michèle; Kahn, Barbara B.; Clement, Karine; Guo-Ping Shi
- Abstract
Cysteine proteases play an important part in human pathobiology. 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 metabolism. 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 β-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 β-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 β-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.
- Subjects
GLUCOSE; CYSTEINE proteinases; FIBRONECTINS; INSULIN; BODY weight; METABOLIC disorders
- Publication
Nature Cell Biology, 2007, Vol 9, Issue 8, p978
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb1623