Institut National de la Santé et de la Recherche Méédicale, Unité 872, Université Pierre et Marie Curie-Paris6, Paris, France.
J Clin Endocrinol Metab. 2010 Apr;95(4):1861-8. doi: 10.1210/jc.2009-1894. Epub 2010 Feb 17.
Recent studies in humans and mice suggest the implication of the cysteine proteases cathepsins S, L, and K in vascular and metabolic complications of obesity.
Our objective was to identify clinically relevant forms of cathepsin in human obesity.
We conducted a prospective study on two independent cohorts.
The first cohort includes 45 obese women eligible for gastric surgery (age, 39 +/- 1.6 yr; body mass index, 47 +/- 0.99 kg/m(2)) and 17 nonobese women (age, 38 +/- 1.8 yr; body mass index, 21 +/- 0.44 kg/m(2)). The second cohort comprises 29 obese women (age, 57 +/- 0.8 yr; body mass index, 34 +/- 0.69 kg/m(2)) undergoing 6 months of medically supervised caloric restriction.
Cathepsin S, L, and K mRNA levels were determined in surgical adipose tissue biopsies. The proteins were measured in conditioned medium of adipose tissue explants and in circulation.
Obese subjects had a 2-fold increase in cathepsin S mRNA in adipose tissue as compared with normal-weight subjects and an increased rate (1.5-fold) of cathepsin S release in adipose tissue explants. Cathepsin S circulating concentrations were increased with obesity (+30%) and reduced after weight reduction (P < 0.05 for both). By contrast, cathepsin L was unaffected in adipose tissue and serum; cathepsin K was undetectable in circulation and unchanged in adipose tissue.
In humans, cathepsin S is more influenced than cathepsins L and K by changes in energy balance in adipose tissue and circulation. This opens new avenues to explore whether selective inhibition of this protease could reduce cardiovascular risk and ameliorate metabolic status in obese subjects.
最近的人体和小鼠研究表明半胱氨酸蛋白酶组织蛋白酶 S、L 和 K 参与肥胖的血管和代谢并发症。
我们的目的是确定人类肥胖症中与临床相关的组织蛋白酶形式。
我们对两个独立的队列进行了前瞻性研究。
第一队列包括 45 名符合胃手术条件的肥胖女性（年龄 39 +/- 1.6 岁；体重指数 47 +/- 0.99 kg/m(2)) 和 17 名非肥胖女性（年龄 38 +/- 1.8 岁；体重指数 21 +/- 0.44 kg/m(2))。第二队列包括 29 名肥胖女性（年龄 57 +/- 0.8 岁；体重指数 34 +/- 0.69 kg/m(2))，接受 6 个月的医学监督热量限制。
在手术脂肪组织活检中确定了组织蛋白酶 S、L 和 K 的 mRNA 水平。在脂肪组织外植体的条件培养基和循环中测量了蛋白质。
与正常体重受试者相比，肥胖受试者的脂肪组织中组织蛋白酶 S mRNA 增加了 2 倍，并且脂肪组织外植体中组织蛋白酶 S 的释放速度增加了 1.5 倍。肥胖症患者的循环组织蛋白酶 S 浓度增加（+30%），体重减轻后降低（两者均 P < 0.05）。相比之下，脂肪组织和血清中的组织蛋白酶 L 不受影响；循环中未检测到组织蛋白酶 K，脂肪组织中无变化。
在人类中，与能量平衡变化相关的脂肪组织和循环中，组织蛋白酶 S 比组织蛋白酶 L 和 K 更受影响。这为探索选择性抑制这种蛋白酶是否可以降低肥胖人群的心血管风险并改善其代谢状况开辟了新途径。
