Elevated UCP1 levels are sufficient to improve glucose uptake in human white adipocytes.

Abstract

Brown adipose tissue (BAT) has been considered beneficial for metabolic health by participating in the regulation of glucose homoeostasis. The browning factors that improve glucose uptake beyond normal levels are still unknown but glucose uptake is not affected in UCP1 knockout mice. Here, we demonstrate in human white adipocytes that basal/resting glucose uptake is improved by solely elevating UCP1 protein levels. Generating human white Simpson-Golabi-Behmel syndrome (SGBS) adipocytes with a stable knockout and overexpression of UCP1, we discovered that UCP1 overexpressing adipocytes significantly improve glucose uptake by 40%. Mechanistically, this is caused by higher glycolytic flux, seen as increased oxygen consumption, extracellular acidification and lactate secretion rates. The improvements in glucose handling are comparable to white-to-brown transitions, as judged by, for the first time, directly comparing in vitro differentiated mouse brown vs white adipocytes. Although no adipogenic, metabolic and mitochondrial gene expressions were significantly altered in SGBS cells, pharmacological inhibition of GLUT1 completely abrogated differences between UCP1+ and control cells, thereby uncovering GLUT1-mediated uptake as permissive gatekeeper. Collectively, our data demonstrate that elevating UCP1 levels is sufficient to improve human white adipocytes as a glucose sink without adverse cellular effects, thus not requiring the adrenergic controlled, complex network of browning which usually hampers translational efforts.

• Authors: D Tews, T Pula, J B Funcke, M Jastroch, M Keuper, K M Debatin, M Wabitsch, P Fischer-Posovszky
• Journal: Redox biology (Redox Biol) Vol. 26 Pg. 101286 (09 2019) ISSN: 2213-2317 [Electronic] Netherlands
• PMID: 31382214 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2019 The Authors. Published by Elsevier B.V. All rights reserved.

Chemical References

• Uncoupling Protein 1
• Glucose

Topics

• Adipocytes, Brown (metabolism)
• Adipocytes, White (metabolism)
• Animals
• Biological Transport
• Gene Expression
• Glucose (metabolism)
• Glycolysis
• Humans
• Mice
• Mitochondria
• Thermogenesis
• Uncoupling Protein 1 (genetics, metabolism)