Translational Metabolic Laboratory, Department of Laboratory Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Department of Internal Medicine, Radboud Institute for Molecular Life Sciences, Radboud University Medical Center, Nijmegen, The Netherlands.
Int J Obes (Lond). 2019 Sep;43(9):1712-1723. doi: 10.1038/s41366-018-0225-8. Epub 2018 Oct 9.
Overweight and obesity can lead to adipose tissue inflammation, which causes insulin resistance and on the long-term type 2 diabetes mellitus (T2D). The inflammatory changes of obese-adipose tissue are characterized by macrophage infiltration and activation, but validated circulating biomarkers for adipose tissue inflammation for clinical use are still lacking. One of the most secreted enzymes by activated macrophages is chitotriosidase (CHIT1).
To test whether circulating CHIT1 enzymatic activity levels reflect adipose tissue inflammation.
Plasma and adipose tissue samples of 105 subjects (35 lean, 37 overweight, and 33 T2D patients) were investigated. CHIT1 mRNA levels were determined in adipose tissue-resident innate immune cells. CHIT1 mRNA levels, protein abundance, and plasma enzymatic activity were subsequently measured in adipose tissue biopsies and plasma of control subjects with varying levels of obesity and adipose tissue inflammation as well as in T2D patients.
In adipose tissue, CHIT1 mRNA levels were higher in stromal vascular cells compared to adipocytes, and higher in adipose tissue-residing macrophages compared to circulating monocytes (p < 0.001). CHIT1 mRNA levels in adipose tissue were enhanced in overweightcompared to lean subjects and even more in T2D patients (p < 0.05). In contrast, plasma CHIT1 enzymatic activity did not differ between lean, overweight subjects and T2D patients. A mutation of the CHIT1 gene decreases plasma CHIT1 activity.
CHIT1 is expressed by adipose tissue macrophages and expression is higher in overweight subjects and T2D patients, indicating its potential as tissue biomarker for adipose tissue inflammation. However, these differences do not translate into different plasma CHIT1 activity levels. Moreover, a common CHIT1 gene mutation causing loss of plasma CHIT1 activity interferes with its use as a biomarker of adipose tissue inflammation. These results indicate that plasma CHIT1 activity is of limited value as a circulating biomarker for adipose tissue inflammation in human subjects.
超重和肥胖会导致脂肪组织炎症，进而导致胰岛素抵抗和长期的 2 型糖尿病（T2D）。肥胖脂肪组织的炎症变化的特征是巨噬细胞浸润和激活，但目前仍缺乏用于临床的验证的脂肪组织炎症的循环生物标志物。激活的巨噬细胞分泌的最主要的酶之一是几丁质酶 1（CHIT1）。
测试循环 CHIT1 酶活性水平是否反映脂肪组织炎症。
研究了 105 名受试者（35 名瘦人，37 名超重者和 33 名 T2D 患者）的血浆和脂肪组织样本。测定脂肪组织驻留固有免疫细胞中的 CHIT1mRNA 水平。随后在脂肪组织活检和具有不同肥胖程度和脂肪组织炎症的对照受试者以及 T2D 患者的血浆中测量 CHIT1mRNA 水平、蛋白丰度和血浆酶活性。
在脂肪组织中，CHIT1mRNA 水平在基质血管细胞中高于脂肪细胞，在脂肪组织驻留的巨噬细胞中高于循环单核细胞（p<0.001）。与瘦人相比，超重者的脂肪组织 CHIT1mRNA 水平升高，而 T2D 患者的水平更高（p<0.05）。相比之下，瘦人、超重者和 T2D 患者的血浆 CHIT1 酶活性没有差异。CHIT1 基因的突变会降低血浆 CHIT1 活性。
CHIT1 由脂肪组织巨噬细胞表达，在超重者和 T2D 患者中表达更高，表明其作为脂肪组织炎症的组织生物标志物的潜力。然而，这些差异并未转化为不同的血浆 CHIT1 活性水平。此外，导致血浆 CHIT1 活性丧失的常见 CHIT1 基因突变会干扰其作为脂肪组织炎症生物标志物的使用。这些结果表明，在人体中，血浆 CHIT1 活性作为脂肪组织炎症的循环生物标志物的价值有限。
