posted on 2021-07-15, 14:05authored byHan-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.