Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Centre+ , Maastricht, The Netherlands.
Adipocyte. 2020 Jan 1;9(1):246-252. doi: 10.1080/21623945.2020.1775035.
Cathepsin L1 (CTSL1) and B (CTSB) are lysosomal proteases, of which the expression and activity are impaired in adipose tissue (AT) of obese rodents, indicating AT lysosomal dysfunction. Here we assess the relation between abdominal subcutaneous AT (SCAT) CTSL1 and CTSB expression (qRT-PCR), body composition and tissue-specific insulin resistance in 77 overweight/obese (BMI: 225.6-38.6 kg/m) well phenotyped men and women (61 M/16 F). A two-step hyperinsulinemic-euglycemic clamp was performed to assess AT, hepatic and skeletal muscle insulin sensitivity. Our data show that reduced CTSB expression is associated with markers of insulin resistance (standardized β = -0.561, p < 0.001), independent of adiposity, while CTSL1 expression is only associated with markers of body composition. Our data suggest the presence of lysosomal dysfunction in SCAT of obese humans with an impaired glucose homoeostasis. However, this needs to be investigated in more detail in future mechanistic studies.
组织蛋白酶 L1（CTSL1）和 B（CTSB）是溶酶体蛋白酶，其在肥胖啮齿动物的脂肪组织（AT）中的表达和活性受损，表明 AT 溶酶体功能障碍。在这里，我们评估了 77 名超重/肥胖（BMI：225.6-38.6 kg/m）的男性和女性中腹部皮下脂肪组织（SCAT）CTSL1 和 CTSB 表达（qRT-PCR）、身体成分和组织特异性胰岛素抵抗之间的关系（61 名男性/16 名女性）。进行了两步高胰岛素-正常血糖钳夹术以评估 AT、肝和骨骼肌胰岛素敏感性。我们的数据表明，CTSB 表达降低与胰岛素抵抗标志物相关（标准化 β=-0.561，p<0.001），与肥胖无关，而 CTSL1 表达仅与身体成分标志物相关。我们的数据表明，肥胖人群的 SCAT 中存在溶酶体功能障碍，其葡萄糖稳态受损。然而，这需要在未来的机制研究中进行更详细的研究。
