The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose

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‐g...

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Bibliographic Details
Published in:	Obesity (Silver Spring, Md.) Vol. 32; no. 8; pp. 1526 - 1540
Main Authors:	Mashayekhi, Mona, Sheng, Quanhu, Bailin, Samuel S., Massier, Lucas, Zhong, Jiawei, Shi, Mingjian, Wanjalla, Celestine N., Wang, Thomas J., Ikizler, T. Alp, Niswender, Kevin D., Gabriel, Curtis L., Palacios, Julia, Turgeon‐Jones, Rachel, Reynolds, Cassandra F., Luther, James M., Brown, Nancy J., Das, Saumya, Dahlman, Ingrid, Mosley, Jonathan D., Koethe, John R., Rydén, Mikael, Bachmann, Katherine N., Shah, Ravi V.
Format:	Journal Article
Language:	English
Published:	United States 01-08-2024
Subjects:	Medicin och hälsovetenskap
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Summary:	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.
Bibliography:	Mona Mashayekhi, Quanhu Sheng, Samuel S. Bailin, Lucas Massier, John R. Koethe, Mikael Rydén, Katherine N. Bachmann, and Ravi V. Shah contributed equally to this study. ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23
ISSN:	1930-7381 1930-739X 1930-739X
DOI:	10.1002/oby.24064