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Subcutaneous Adipose Tissue Metabolic Function and Insulin Sensitivity in People with Obesity

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posted on 15.07.2021, 14:05 by Han-Chow E. Koh, Stephan van Vliet, Terri A. Pietka, Gretchen A. Meyer, Babak Razani, Richard Laforest, Robert J Gropler, Bettina Mittendorfer
We used stable isotope-labeled glucose and palmitate tracer infusions, a hyperinsulinemic-euglycemic clamp, positron-emission tomography of muscles and adipose tissue after [18F]fluorodeoxyglucose and [15O]water injections, and subcutaneous adipose tissue (SAT) biopsy to test the hypotheses that: i) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin-sensitive, and ii) putative SAT factors thought to cause insulin resistance are present in people with obesity who are insulin-resistant but not in those who are insulin-sensitive. We found high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT, but was due to high insulin-stimulated muscle glucose uptake. Furthermore, insulin-stimulated muscle glucose uptake was not different between insulin-sensitive obese and lean participants even though adipocytes were larger, SAT perfusion and oxygenation were lower, and markers of SAT inflammation, fatty acid appearance in plasma in relation to fat-free mass, and plasma fatty acid concentration were higher in the insulin-sensitive obese than lean participants. In addition, we observed only marginal or no differences in adipocyte size, SAT perfusion and oxygenation, and markers of SAT inflammation between insulin-resistant and insulin-sensitive obese participants. Plasma fatty acid concentration was also not different between insulin-sensitive and insulin-resistant obese participants even though SAT was resistant to the inhibitory effect of insulin on lipolysis in the insulin-resistant obese group. These data suggest several putative SAT factors that are commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.

Funding

The work presented in this manuscript was supported by National Institutes of Health grants R01 DK115400, P30 DK56341 (Nutrition Obesity Research Center), P30 DK020579 (Diabetes Research Center), P30 DK052574 (Digestive Disease Research Core Center), and UL1TR000448 (Clinical Translational Science Award), and grants from the American Diabetes Association (1-18-ICTS-119) and the Longer Life Foundation.

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