Cathepsins S, L, and K and Their Pathophysiological Relevance in Obesity
- نوع فایل : کتاب
- زبان : انگلیسی
- مؤلف : Jean-Charles Lafarge Karine Cle´ment Miche`le Guerre-Millo
- چاپ و سال / کشور: 2011
Description
Members of the cysteine protease cathepsin family play an important part in human pathophysiology. Among those, Cathepsin K has a major role in enzymatic bone degradation. Cathepsin K was recently found to be expressed in adipose tissue and increased in obesity. This led to the hypothesis that Cathepsin K and potentially other forms of cathepsin might contribute to obesity and obesitylinked complications. In this context, we identified Cathepsin S gene as one of the most deregulated gene in the adipose tissue of obese subjects, showing a strong correlation with body mass index, while Cathepsin L was also found in high abundance in the adipose tissue of dietinduced and genetically obese mice. Cathepsin K or Cathepsin L deletion in genetically modified mice reduces adiposity and ameliorates glucose homeostasis. The pharmacological inhibition of these cathepsins attenuates body weight gain both in diet-induced and in genetically obese mice and impairs adipose differentiation in cell culture experiments. These data in mice and humans enlighten the unexpected implication of cathepsin family members to promote fat accretion and contribute to the deterioration of glycemic parameters in obesity. Thus, inhibition of specific cathepsins might prove an efficient adjunct to diet and exercise in human obesity, notwithstanding it remains to decipher the cellular and molecular mechanisms implicated.
Clinic Rev Bone Miner Metab (2011) 9:133–137 Published online: 10 June 2011
