Wang Yansu, Yu Haoyong, Ma Xiaojing, Wang Yufei, Liu Weijie, Zhang Hongwei, Chen Wei, Yu Song, Bao Yuqian, Yang Ying
Department of Endocrinology and Metabolism, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai Clinical Center for Diabetes, Shanghai Key Clinical Center for Metabolic Disease, Shanghai Diabetes Institute, Shanghai Key Laboratory of Diabetes Mellitus, Shanghai, China.
Department of General Surgery, Shanghai Jiao Tong University School of Medicine Affiliated Sixth People's Hospital, Shanghai, China.
Diabetes Metab Res Rev. 2023 Oct;39(7):e3688. doi: 10.1002/dmrr.3688. Epub 2023 Jul 6.
Clusterin (encoded by CLU) is a novel adipokine. Serum clusterin levels were elevated in populations with obesity and diabetes. Adipose tissue insulin resistance (Adipo-IR) is proposed as an early metabolic defect that precedes systemic insulin resistance. Herein, we aimed to investigate the relationship between serum clusterin levels and Adipo-IR. CLU expression in human abdominal adipose tissues and clusterin secretion in human adipocytes was also explored.
A total of 201 participants (aged 18-62 years, 139 of whom were obese) were recruited. Enzyme-linked immunosorbent assay was used to measure serum clusterin levels. Adipo-IR was calculated from the product of fasting free fatty acids and fasting insulin levels. Transcriptome sequencing of abdominal visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) was performed. Human adipocytes were used to detect the secretion of clusterin.
Serum clusterin levels were independently associated with Adipo-IR after adjusting for several confounding factors (standardised β = 0.165, p = 0.021). CLU expression in VAT and SAT was associated with obesity-related metabolic risk factors. Higher CLU expression in VAT was accompanied by an increase in collagen accumulation. Clusterin secretion in differentiated human adipocytes was stimulated by insulin and inhibited by rosiglitazone.
Clusterin is strongly associated with Adipo-IR. Serum clusterin may function as an effective indicator of adipose tissue insulin resistance.
簇集蛋白（由CLU编码）是一种新型脂肪因子。肥胖和糖尿病患者的血清簇集蛋白水平升高。脂肪组织胰岛素抵抗（Adipo-IR）被认为是全身性胰岛素抵抗之前的一种早期代谢缺陷。在此，我们旨在研究血清簇集蛋白水平与Adipo-IR之间的关系。我们还探讨了人腹部脂肪组织中CLU的表达以及人脂肪细胞中簇集蛋白的分泌情况。
共招募了201名参与者（年龄在18 - 62岁之间，其中139人肥胖）。采用酶联免疫吸附测定法测量血清簇集蛋白水平。Adipo-IR由空腹游离脂肪酸和空腹胰岛素水平的乘积计算得出。对腹部内脏脂肪组织（VAT）和皮下脂肪组织（SAT）进行转录组测序。用人脂肪细胞检测簇集蛋白的分泌情况。
在调整了几个混杂因素后，血清簇集蛋白水平与Adipo-IR独立相关（标准化β = 0.165，p = 0.021）。VAT和SAT中CLU的表达与肥胖相关的代谢危险因素有关。VAT中较高的CLU表达伴随着胶原蛋白积累的增加。胰岛素刺激分化的人脂肪细胞分泌簇集蛋白，但罗格列酮抑制该分泌。
簇集蛋白与Adipo-IR密切相关。血清簇集蛋白可能作为脂肪组织胰岛素抵抗的有效指标发挥作用。
