MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism

Abstract Adipose tissue takes up glucose and releases lactate, thereby contributing significantly to systemic glucose and lactate homeostasis. This implies the necessity of upregulation of net acid and lactate flux capacity during adipocyte differentiation and function. However, the regulation of la...

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Autores principales: Charlotte Petersen, Mette D. Nielsen, Elise S. Andersen, Astrid L. Basse, Marie S. Isidor, Lasse K. Markussen, Birgitte M. Viuff, Ian H. Lambert, Jacob B. Hansen, Stine F. Pedersen
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Publicado: Nature Portfolio 2017
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spelling oai:doaj.org-article:8bf3e0267a624fd6a5bb3adcd9b1f5ba2021-12-02T15:06:00ZMCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism10.1038/s41598-017-13298-z2045-2322https://doaj.org/article/8bf3e0267a624fd6a5bb3adcd9b1f5ba2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-13298-zhttps://doaj.org/toc/2045-2322Abstract Adipose tissue takes up glucose and releases lactate, thereby contributing significantly to systemic glucose and lactate homeostasis. This implies the necessity of upregulation of net acid and lactate flux capacity during adipocyte differentiation and function. However, the regulation of lactate- and acid/base transporters in adipocytes is poorly understood. Here, we tested the hypothesis that adipocyte thermogenesis, browning and differentiation are associated with an upregulation of plasma membrane lactate and acid/base transport capacity that in turn is important for adipocyte metabolism. The mRNA and protein levels of the lactate-H+ transporter MCT1 and the Na+,HCO3 − cotransporter NBCe1 were upregulated in mouse interscapular brown and inguinal white adipose tissue upon cold induction of thermogenesis and browning. MCT1, MCT4, and NBCe1 were furthermore strongly upregulated at the mRNA and protein level upon differentiation of cultured pre-adipocytes. Adipocyte differentiation was accompanied by increased plasma membrane lactate flux capacity, which was reduced by MCT inhibition and by MCT1 knockdown. Finally, in differentiated brown adipocytes, glycolysis (assessed as ECAR), and after noradrenergic stimulation also oxidative metabolism (OCR), was decreased by MCT inhibition. We suggest that upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated HCO3 −/pH homeostasis are important for the physiological function of mature adipocytes.Charlotte PetersenMette D. NielsenElise S. AndersenAstrid L. BasseMarie S. IsidorLasse K. MarkussenBirgitte M. ViuffIan H. LambertJacob B. HansenStine F. PedersenNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-13 (2017)
institution DOAJ
collection DOAJ
language EN
topic Medicine
R
Science
Q
spellingShingle Medicine
R
Science
Q
Charlotte Petersen
Mette D. Nielsen
Elise S. Andersen
Astrid L. Basse
Marie S. Isidor
Lasse K. Markussen
Birgitte M. Viuff
Ian H. Lambert
Jacob B. Hansen
Stine F. Pedersen
MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism
description Abstract Adipose tissue takes up glucose and releases lactate, thereby contributing significantly to systemic glucose and lactate homeostasis. This implies the necessity of upregulation of net acid and lactate flux capacity during adipocyte differentiation and function. However, the regulation of lactate- and acid/base transporters in adipocytes is poorly understood. Here, we tested the hypothesis that adipocyte thermogenesis, browning and differentiation are associated with an upregulation of plasma membrane lactate and acid/base transport capacity that in turn is important for adipocyte metabolism. The mRNA and protein levels of the lactate-H+ transporter MCT1 and the Na+,HCO3 − cotransporter NBCe1 were upregulated in mouse interscapular brown and inguinal white adipose tissue upon cold induction of thermogenesis and browning. MCT1, MCT4, and NBCe1 were furthermore strongly upregulated at the mRNA and protein level upon differentiation of cultured pre-adipocytes. Adipocyte differentiation was accompanied by increased plasma membrane lactate flux capacity, which was reduced by MCT inhibition and by MCT1 knockdown. Finally, in differentiated brown adipocytes, glycolysis (assessed as ECAR), and after noradrenergic stimulation also oxidative metabolism (OCR), was decreased by MCT inhibition. We suggest that upregulation of MCT1- and MCT4-mediated lactate flux capacity and NBCe1-mediated HCO3 −/pH homeostasis are important for the physiological function of mature adipocytes.
format article
author Charlotte Petersen
Mette D. Nielsen
Elise S. Andersen
Astrid L. Basse
Marie S. Isidor
Lasse K. Markussen
Birgitte M. Viuff
Ian H. Lambert
Jacob B. Hansen
Stine F. Pedersen
author_facet Charlotte Petersen
Mette D. Nielsen
Elise S. Andersen
Astrid L. Basse
Marie S. Isidor
Lasse K. Markussen
Birgitte M. Viuff
Ian H. Lambert
Jacob B. Hansen
Stine F. Pedersen
author_sort Charlotte Petersen
title MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism
title_short MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism
title_full MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism
title_fullStr MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism
title_full_unstemmed MCT1 and MCT4 Expression and Lactate Flux Activity Increase During White and Brown Adipogenesis and Impact Adipocyte Metabolism
title_sort mct1 and mct4 expression and lactate flux activity increase during white and brown adipogenesis and impact adipocyte metabolism
publisher Nature Portfolio
publishDate 2017
url https://doaj.org/article/8bf3e0267a624fd6a5bb3adcd9b1f5ba
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