IL-27 increases energy storage in white adipocytes by enhancing glucose uptake and fatty acid esterification

ABSTRACT

The cytokine interleukin (IL)-27 has been reported to induce thermogenesis in white adipocytes. However, it remains unknown whether IL-27-mediated adipocyte energy dissipation is paralleled by an elevated energy supply from lipids and/or carbohydrates. We hypothesized that IL-27 increases lipolysis and glucose uptake in white adipocytes, thereby providing substrates for thermogenesis. Unexpectedly, we found that treatment of 3T3-L1 adipocytes with IL-27 reduced intra- and extracellular free fatty acid (FFA) concentrations and that phosphorylation of hormone-sensitive lipase (HSL) was not affected by IL-27. These results were confirmed in subcutaneous white adipocytes. Further, application of IL-27 to 3T3-L1 adipocytes increased intracellular triglyceride (TG) content but not mitochondrial ATP production nor expression of enzymes involved in beta-oxidation indicating that elevated esterification rather than oxidation causes FFA disappearance. In addition, IL-27 significantly increased GLUT1 protein levels, basal glucose uptake as well as glycolytic ATP production, suggesting that increased glycolytic flux due to IL-27 provides the glycerol backbone for TG synthesis. In conclusion, our findings suggest IL-27 increases glucose uptake and TG deposition in white adipocytes.

KEYWORDS:

• Free fatty acid
• triglyceride
• lipolysis
• obesity
• white adipose tissue

Acknowledgements

We thank D Sean Froese (University of Zurich) for proof reading and language editing.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Author contribution

C.S. designed and performed experiments and analysed data. A.S. performed experiments and analysed data. D.K. and S.W. designed experiments, analysed data and wrote the manuscript. All authors reviewed and commented on the manuscript.

Supplementary material

Supplemental data for this article can be accessed online at https://doi.org/10.1080/21623945.2023.2276346.

Additional information

Funding

This work was supported by a grant from the Swiss National Science Foundation (#310030-179344 and #310030-215451 to DK).