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 charaterized the WAT and the metabolic phenotype of ctsk deficient animals (ctsk -/-). When the growth rate ctsk-Tγ- was compared to that of the wild type animals (WT), we could establish a time window (5-8 weeks of age) within whkh ctsk-/-display significantly lower body weight and WAT size as compared to WT, Such a difference was not observable in alder 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 accumulatioh 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. © 2007 Funicello et al.

Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores / M. Funicello, M. Novelli, M. Ragni, T. Vottari, C. Cocuzza, J. Soriano-Lopez, C. Chiellini, F. Boschi, P. Marzola, P. Masiello, P. Saftig, F. Santini, R. St-Jacques, S. Desmarais, N. Morin, J. Mancini, M.D. Percival, A. Pinchera, M. Maffei. - In: PLOS ONE. - ISSN 1932-6203. - 2:8(2007 Aug), pp. e683.1-e683.12. [10.1371/journal.pone.0000683]

Cathepsin K null mice show reduced adiposity during the rapid accumulation of fat stores

M. Ragni;
2007

Abstract

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 charaterized the WAT and the metabolic phenotype of ctsk deficient animals (ctsk -/-). When the growth rate ctsk-Tγ- was compared to that of the wild type animals (WT), we could establish a time window (5-8 weeks of age) within whkh ctsk-/-display significantly lower body weight and WAT size as compared to WT, Such a difference was not observable in alder 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 accumulatioh 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. © 2007 Funicello et al.
Settore MED/49 - Scienze Tecniche Dietetiche Applicate
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Utilizza questo identificativo per citare o creare un link a questo documento: https://hdl.handle.net/2434/951292
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