Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores
Funicello, Marcella (University Hospital of Pisa (Pisa, Itàlia))
Novelli, Michela (University of Pisa. Department of Experimental Pathology, Medical Biotechnologies, Infectivology and Epidemiology)
Ragni, Maurizio (University Hospital of Pisa (Pisa, Itàlia))
Vottari, Teresa (University Hospital of Pisa (Pisa, Itàlia))
Cocuzza, Cesare (University Hospital of Pisa (Pisa, Itàlia))
López-Soriano, Joaquín (University Hospital of Pisa (Pisa, Itàlia))
Chiellini, Chiara (University Hospital of Pisa (Pisa, Itàlia))
Boschi, Federico (University of Verona (Verona, Itàlia). Department of Morphological-Biomedical Sciences)
Marzola, Pasquina (University of Verona (Verona, Itàlia). Department of Morphological-Biomedical Sciences)
Masiello, Pellegrino (University of Pisa. Department of Experimental Pathology, Medical Biotechnologies, Infectivology and Epidemiology)
Saftig, Paul (Christian-Albrechts University (Kiel, Alemanya). Biochemical Institute)
Santini, Ferruccio (Christian-Albrechts University (Kiel, Alemanya). Biochemical Institute)
St-Jacques, René (Merck Frosst Centre for Therapeutic Research (Kirkland, Canadà))
Desmarais, Sylvie (Merck Frosst Centre for Therapeutic Research (Kirkland, Canadà))
Morin, Nicolas (Merck Frosst Centre for Therapeutic Research (Kirkland, Canadà))
Mancini, Joseph (Merck Frosst Centre for Therapeutic Research (Kirkland, Canadà))
Percival, M. David (Merck Frosst Centre for Therapeutic Research (Kirkland, Canadà))
Pinchera, Aldo (University Hospital of Pisa (Pisa, Itàlia))
Maffei, Margherita (University Hospital of Pisa (Pisa, Itàlia))

Fecha:	2007
Resumen:	Growing evidences indicate that proteases are implicated in adipogenesis and in the onset of obesity. We previously reported that the cysteine protease cathepsin K (ctsk) is overexpressed in the white adipose tissue (WAT) of obese individuals. We herein characterized the WAT and the metabolic phenotype of ctsk deficient animals (ctsk−/−). When the growth rate of ctsk−/− was compared to that of the wild type animals (WT), we could establish a time window (5-8 weeks of age) within which ctsk−/−display significantly lower body weight and WAT size as compared to WT. Such a difference was not observable in older mice. Upon treatment with high fat diet (HFD) for 12 weeks ctsk−/− gained significantly less weight than WT and showed reduced brown adipose tissue, liver mass and a lower percentage of body fat. Plasma triglycerides, cholesterol and leptin were significantly lower in HFD-fed-ctsk−/− as compared to HFD-fed WT animals. Adipocyte lipolysis rates were increased in both young and HFD-fed-ctsk−/−, as compared to WT. Carnitine palmitoyl transferase-1 activity, was higher in mitochondria isolated from the WAT of HFD treated ctsk−/− as compared to WT. Together, these data indicate that ctsk ablation in mice results in reduced body fat content under conditions requiring a rapid accumulation of fat stores. This observation could be partly explained by an increased release and/or utilization of FFA and by an augmented ratio of lipolysis/lipogenesis. These results also demonstrate that under a HFD, ctsk deficiency confers a partial resistance to the development of dyslipidemia.
Derechos:	Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.
Lengua:	Anglès
Documento:	Article ; Versió publicada
Materia:	Obesitat ; Cysteine protease cathepsin K ; White adipose tissue
Publicado en:	PloS one, Vol. 2, Issue 8 (August 2007) , p. e683, ISSN 1932-6203

DOI: 10.1371/journal.pone.0000683
PMID: 17668061

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