皮下脂肪转录组确定了与内脏脂肪共享的胰岛素抵抗分子特征。
The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.
机构信息
Division of Diabetes, Endocrinology and Metabolism, Department of Medicine, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
Department of Biostatistics, Vanderbilt University Medical Center, Nashville, Tennessee, USA.
出版信息
Obesity (Silver Spring). 2024 Aug;32(8):1526-1540. doi: 10.1002/oby.24064. Epub 2024 Jul 5.
OBJECTIVE
The objective of this study was to identify the transcriptional landscape of insulin resistance (IR) in subcutaneous adipose tissue (SAT) in humans across the spectrum of obesity.
METHODS
We used SAT RNA sequencing in 220 individuals with metabolic phenotyping.
RESULTS
We identified a 35-gene signature with high predictive accuracy for homeostatic model of IR that was expressed across a variety of non-immune cell populations. We observed primarily "protective" IR associations for adipocyte transcripts and "deleterious" associations for macrophage transcripts, as well as a high concordance between SAT and visceral adipose tissue (VAT). Multiple SAT genes exhibited dynamic expression 5 years after weight loss surgery and with insulin stimulation. Using available expression quantitative trait loci in SAT and/or VAT, we demonstrated similar genetic effect sizes of SAT and VAT on type 2 diabetes and BMI.
CONCLUSIONS
SAT is conventionally viewed as a metabolic buffer for lipid deposition during positive energy balance, whereas VAT is viewed as a dominant contributor to and prime mediator of IR and cardiometabolic disease risk. Our results implicate a dynamic transcriptional architecture of IR that resides in both immune and non-immune populations in SAT and is shared with VAT, nuancing the current VAT-centric concept of IR in humans.
目的
本研究旨在确定肥胖人群中，人类皮下脂肪组织（SAT）中胰岛素抵抗（IR）的转录特征。
方法
我们对 220 名具有代谢表型的个体进行了 SAT RNA 测序。
结果
我们发现了一个具有高预测准确性的 35 基因特征，可用于稳态模型评估胰岛素抵抗，该特征在各种非免疫细胞群体中均有表达。我们观察到脂肪细胞转录物主要表现出“保护”的 IR 相关性，而巨噬细胞转录物则表现出“有害”的相关性，并且 SAT 和内脏脂肪组织（VAT）之间具有高度一致性。减肥手术后 5 年和胰岛素刺激后，多个 SAT 基因表现出动态表达。利用 SAT 和/或 VAT 中可用的表达数量性状基因座，我们证明了 SAT 和 VAT 对 2 型糖尿病和 BMI 的遗传效应大小相似。
结论
SAT 通常被视为在正能平衡期间脂肪沉积的代谢缓冲器，而 VAT 被视为 IR 和代谢性心血管疾病风险的主要贡献者和主要介质。我们的结果表明，IR 具有动态的转录结构，存在于 SAT 的免疫和非免疫群体中，并与 VAT 共享，这使当前以 VAT 为中心的人类 IR 概念更加细致。
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