The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.
Obesity (Silver Spring)
; 32(8): 1526-1540, 2024 08.
Article
em En
| MEDLINE
| ID: mdl-38967296
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.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Resistência à Insulina
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Gordura Intra-Abdominal
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Gordura Subcutânea
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Transcriptoma
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Obesidade
Limite:
Adult
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article