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Decreased adipose tissue oxygenation associates with insulin resistance in individuals with obesity.

Citation
Cifarelli, V., et al. “Decreased Adipose Tissue Oxygenation Associates With Insulin Resistance In Individuals With Obesity.”. The Journal Of Clinical Investigation, pp. 6688-6699.
Center Washington University in St Louis
Author Vincenza Cifarelli, Scott C Beeman, Gordon I Smith, Jun Yoshino, Darya Morozov, Joseph W Beals, Brandon D Kayser, Jeramie D Watrous, Mohit Jain, Bruce W Patterson, Samuel Klein
Keywords Adipose tissue, glucose metabolism, Metabolism, obesity
Abstract

BACKGROUNDData from studies conducted in rodent models have shown that decreased adipose tissue (AT) oxygenation is involved in the pathogenesis of obesity-induced insulin resistance. Here, we evaluated the potential influence of AT oxygenation on AT biology and insulin sensitivity in people.METHODSWe evaluated subcutaneous AT oxygen partial pressure (pO2); liver and whole-body insulin sensitivity; AT expression of genes and pathways involved in inflammation, fibrosis, and branched-chain amino acid (BCAA) catabolism; systemic markers of inflammation; and plasma BCAA concentrations, in 3 groups of participants that were rigorously stratified by adiposity and insulin sensitivity: metabolically healthy lean (MHL; n = 11), metabolically healthy obese (MHO; n = 15), and metabolically unhealthy obese (MUO; n = 20).RESULTSAT pO2 progressively declined from the MHL to the MHO to the MUO group, and was positively associated with hepatic and whole-body insulin sensitivity. AT pO2 was positively associated with the expression of genes involved in BCAA catabolism, in conjunction with an inverse relationship between AT pO2 and plasma BCAA concentrations. AT pO2 was negatively associated with AT gene expression of markers of inflammation and fibrosis. Plasma PAI-1 increased from the MHL to the MHO to the MUO group and was negatively correlated with AT pO2, whereas the plasma concentrations of other cytokines and chemokines were not different among the MHL and MUO groups.CONCLUSIONThese results support the notion that reduced AT oxygenation in individuals with obesity contributes to insulin resistance by increasing plasma PAI-1 concentrations and decreasing AT BCAA catabolism and thereby increasing plasma BCAA concentrations.TRIAL REGISTRATIONClinicalTrials.gov NCT02706262.FUNDINGThis study was supported by NIH grants K01DK109119, T32HL130357, K01DK116917, R01ES027595, P42ES010337, DK56341 (Nutrition Obesity Research Center), DK20579 (Diabetes Research Center), DK052574 (Digestive Disease Research Center), and UL1TR002345 (Clinical and Translational Science Award); NIH Shared Instrumentation Grants S10RR0227552, S10OD020025, and S10OD026929; and the Foundation for Barnes-Jewish Hospital.

Year of Publication
2020
Journal
The Journal of clinical investigation
Volume
130
Issue
12
Number of Pages
6688-6699
Date Published
12/2020
ISSN Number
1558-8238
DOI
10.1172/JCI141828
Alternate Journal
J Clin Invest
PMID
33164985
PMCID
PMC7685757
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