1. The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.
- Author
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Mashayekhi M, Sheng Q, Bailin SS, Massier L, Zhong J, Shi M, Wanjalla CN, Wang TJ, Ikizler TA, Niswender KD, Gabriel CL, Palacios J, Turgeon-Jones R, Reynolds CF, Luther JM, Brown NJ, Das S, Dahlman I, Mosley JD, Koethe JR, Rydén M, Bachmann KN, and Shah RV
- Subjects
- Humans, Male, Female, Middle Aged, Adult, Diabetes Mellitus, Type 2 metabolism, Diabetes Mellitus, Type 2 genetics, Body Mass Index, Adipocytes metabolism, Quantitative Trait Loci, Insulin Resistance, Intra-Abdominal Fat metabolism, Subcutaneous Fat metabolism, Transcriptome, Obesity genetics, Obesity metabolism
- Abstract
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., (© 2024 The Authors. Obesity published by Wiley Periodicals LLC on behalf of The Obesity Society.)
- Published
- 2024
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