The subcutaneous adipose transcriptome identifies a molecular signature of insulin resistance shared with visceral adipose.
Obesity (Silver Spring)
; 32(8): 1526-1540, 2024 Aug.
Article
in 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.
Full text:
1
Collection:
01-internacional
Database:
MEDLINE
Main subject:
Insulin Resistance
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Intra-Abdominal Fat
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Subcutaneous Fat
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Transcriptome
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Obesity
Limits:
Adult
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Female
/
Humans
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Male
/
Middle aged
Language:
En
Journal:
Obesity (Silver Spring)
Journal subject:
CIENCIAS DA NUTRICAO
/
FISIOLOGIA
/
METABOLISMO
Year:
2024
Type:
Article
Affiliation country:
United States