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

Diabetes. 2021 Oct;70(10):2225-2236. doi: 10.2337/db21-0160. Epub 2021 Jul 15.


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 1) increased glucose uptake in SAT is responsible for high insulin-stimulated whole-body glucose uptake in people with obesity who are insulin sensitive and 2) 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 that high insulin-stimulated whole-body glucose uptake in insulin-sensitive participants with obesity was not due to channeling of glucose into SAT but, rather, 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 in 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 that several putative SAT factors commonly implicated in causing insulin resistance are normal consequences of SAT expansion unrelated to insulin resistance.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Body Composition / physiology
  • Case-Control Studies
  • Female
  • Glucose / metabolism
  • Glucose Clamp Technique
  • Humans
  • Insulin / pharmacology
  • Insulin Resistance / physiology*
  • Lipolysis / drug effects
  • Male
  • Middle Aged
  • Obesity / metabolism*
  • Obesity / pathology
  • Subcutaneous Fat / drug effects
  • Subcutaneous Fat / metabolism*
  • Subcutaneous Fat / pathology


  • Insulin
  • Glucose

Associated data

  • figshare/10.2337/figshare.14939088