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Ibrahim A, Neinast MD, Li K, et al. Insulin-stimulated adipocytes secrete lactate to promote endothelial fatty acid uptake and transport. J Cell Sci. 2021;135(5)doi: 10.1242/jcs.258964.
Ibrahim, A., Neinast, M. D., Li, K., Noji, M., Kim, B., Bornstein, M. R., Mohammed, R., Wellen, K. E., & Arany, Z. (2022). Insulin-stimulated adipocytes secrete lactate to promote endothelial fatty acid uptake and transport. Journal of cell science, 135(5), . https://doi.org/10.1242/jcs.258964
Ibrahim, Ayon, et al. "Insulin-stimulated adipocytes secrete lactate to promote endothelial fatty acid uptake and transport." Journal of cell science vol. 135,5 (2022). doi: https://doi.org/10.1242/jcs.258964
Ibrahim A, Neinast MD, Li K, Noji M, Kim B, Bornstein MR, Mohammed R, Wellen KE, Arany Z. Insulin-stimulated adipocytes secrete lactate to promote endothelial fatty acid uptake and transport. J Cell Sci. 2022 Mar 01;135(5). doi: 10.1242/jcs.258964. Epub 2021 Dec 16. PMID: 34779480; PMCID: PMC8729779.
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J Cell Sci. 2022 Mar 01;135(5). doi: 10.1242/jcs.258964. Epub 2021 Dec 16.

Insulin-stimulated adipocytes secrete lactate to promote endothelial fatty acid uptake and transport.

Journal of cell science

Ayon Ibrahim, Michael D Neinast, Kristina Li, Michael Noji, Boa Kim, Marc R Bornstein, Raffiu Mohammed, Kathryn E Wellen, Zoltan Arany

Affiliations

  1. Cardiovascular Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
  2. Department of Cancer Biology and Abramson Family Cancer Research Institute, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.

PMID: 34779480 PMCID: PMC8729779 DOI: 10.1242/jcs.258964

Abstract

Insulin stimulates adipose tissue to extract fatty acids from circulation and sequester them inside adipose cells. How fatty acids are transported across the capillary endothelial barrier, and how this process is regulated, remains unclear. We modeled the relationship of adipocytes and endothelial cells in vitro to test the role of insulin in fatty acid transport. Treatment of endothelial cells with insulin did not affect endothelial fatty acid uptake, but endothelial cells took up more fatty acids when exposed to medium conditioned by adipocytes treated with insulin. Manipulations of this conditioned medium indicated that the secreted factor is a small, hydrophilic, non-proteinaceous metabolite. Factor activity was correlated with lactate concentration, and inhibition of lactate production in adipocytes abolished the activity. Finally, lactate alone was sufficient to increase endothelial uptake of both free fatty acids and lipids liberated from chylomicrons, and to promote transendothelial transport, at physiologically relevant concentrations. Taken together, these data suggest that insulin drives adipocytes to secrete lactate, which then acts in a paracrine fashion to promote fatty acid uptake and transport across the neighboring endothelial barrier.

© 2021. Published by The Company of Biologists Ltd.

Keywords: Adipose tissue; Chylomicrons; Endothelium; Fatty acid uptake; Fatty acids; Lactate; Lipid droplet; Paracrine

Conflict of interest statement

Competing interests The authors declare no competing or financial interests.

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