Adipocyte and Cell Biology

Usefulness of surrogate markers to determine insulin action in fat cells

Abstract

Background

Obesity is a major factor behind insulin resistance. The validity of simple biochemical surrogate measures to estimate insulin resistance at the fat cell level is unclear.

Objective

To investigate if the surrogate measures HOMA-IR (glucose/insulin product) and Adipo-IR (fatty acids/insulin product) reflect insulin action on glucose/lipid metabolism in fat cells.

Design

Insulin-induced lipogenesis and lipolysis inhibition (antilipolysis) in subcutaneous fat cells were investigated for sensitivity (reflecting receptor-near events) and responsiveness (i.e., maximum action reflecting distal post-receptor events) in 363 subjects. Results were compared with log10 transformed values for HOMA-IR and Adipo-IR.

Results

Individually, the four measures of in vitro insulin action on fat cells correlated significantly (p < 0.0001) but weakly with each other (adjusted r2 0.05–0.23). HOMA-IR and Adipo-IR correlated strongly with each other (adjusted r2 = 0.81). Using Spearman or simple linear regression all in vitro measures except antilipolytic responsiveness expressed per lipid weight, correlated significantly with Adipo-IR or HOMA-IR (p values <0.0001). Similar relationships remained after combined correction for age, body mass index and sex. Together, the four in vitro measures explained 50% of the variability in HOMA-IR and ADIPO-IR (p < 0.0001). Receiver-operating characteristic analysis showed good sensitivity and specificity for Adipo-IR and HOMA-IR to detect combined insulin resistance of antilipolysis and lipogenesis in fat cells (area under the curve = 0.8).

Conclusions

Insulin action at the receptor and post-receptor levels on lipolysis and lipogenesis in fat cells correlates significantly with Adipo-IR and HOMA-IR. Both surrogate measures give similar information about insulin resistance of glucose and lipid metabolism in fat cells.

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Fig. 1: Relationship between in vitro or in vivo insulin action parameters.
Fig. 2: Sensitivity and specificity of Adipo-IR and HOMA-IR to detect fat cell insulin resistance.

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Acknowledgements

The excellent technical assistance of Britt-Marie Leijonhufvud, Katarina Hertel, Yvonne Widlund, Eva Sjölin, Kerstin Wåhlén, Ana Maria Suzuki, Thais de Castro-Barbosa, and Gaby Åström is greatly appreciated. The study was supported by grants from Swedish Research Council, Knut and Alice Wallenberg’s foundation, Novo Nordisk Foundation (including the Tripartite Immuno-metabolism Consortium Grant Number NNF15CC0018486 and the MSAM consortium NNF15SA0018346), Stockholm County Council, CIMED, the Strategic Research Program in Diabetes at Karolinska Institutet and the Swedish Society of Medicine.

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PA and MR designed the study, wrote the first version of the MS and are the guarantors of the work. All authors analyzed data, contributed to further writing, and accepted the final version of the paper.

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Correspondence to Mikael Rydén or Peter Arner.

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Rydén, M., Andersson, D.P. & Arner, P. Usefulness of surrogate markers to determine insulin action in fat cells. Int J Obes (2020). https://doi.org/10.1038/s41366-020-0592-9

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