Cargando…

Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis

Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by...

Descripción completa

Detalles Bibliográficos
Autores principales: Zhu, Yi, Li, Na, Huang, Mingyang, Bartels, Mason, Dogné, Sophie, Zhao, Shangang, Chen, Xi, Crewe, Clair, Straub, Leon, Vishvanath, Lavanya, Zhang, Zhuzhen, Shao, Mengle, Yang, Yongjie, Gliniak, Christy M., Gordillo, Ruth, Smith, Gordon I., Holland, William L., Gupta, Rana K., Dong, Bingning, Caron, Nathalie, Xu, Yong, Akgul, Yucel, Klein, Samuel, Scherer, Philipp E.
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355239/
https://www.ncbi.nlm.nih.gov/pubmed/34376643
http://dx.doi.org/10.1038/s41467-021-25025-4
_version_ 1783736722945736704
author Zhu, Yi
Li, Na
Huang, Mingyang
Bartels, Mason
Dogné, Sophie
Zhao, Shangang
Chen, Xi
Crewe, Clair
Straub, Leon
Vishvanath, Lavanya
Zhang, Zhuzhen
Shao, Mengle
Yang, Yongjie
Gliniak, Christy M.
Gordillo, Ruth
Smith, Gordon I.
Holland, William L.
Gupta, Rana K.
Dong, Bingning
Caron, Nathalie
Xu, Yong
Akgul, Yucel
Klein, Samuel
Scherer, Philipp E.
author_facet Zhu, Yi
Li, Na
Huang, Mingyang
Bartels, Mason
Dogné, Sophie
Zhao, Shangang
Chen, Xi
Crewe, Clair
Straub, Leon
Vishvanath, Lavanya
Zhang, Zhuzhen
Shao, Mengle
Yang, Yongjie
Gliniak, Christy M.
Gordillo, Ruth
Smith, Gordon I.
Holland, William L.
Gupta, Rana K.
Dong, Bingning
Caron, Nathalie
Xu, Yong
Akgul, Yucel
Klein, Samuel
Scherer, Philipp E.
author_sort Zhu, Yi
collection PubMed
description Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma HA. Instead, an HA-driven systemic substrate redistribution and adipose tissue-liver crosstalk contributes to the systemic glucose improvements. In summary, we demonstrate an unexpected improvement in glucose metabolism as a consequence of HA overproduction in adipose tissue, which argues against the use of systemic HA synthesis inhibitors to treat obesity and T2D.
format Online
Article
Text
id pubmed-8355239
institution National Center for Biotechnology Information
language English
publishDate 2021
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-83552392021-08-30 Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis Zhu, Yi Li, Na Huang, Mingyang Bartels, Mason Dogné, Sophie Zhao, Shangang Chen, Xi Crewe, Clair Straub, Leon Vishvanath, Lavanya Zhang, Zhuzhen Shao, Mengle Yang, Yongjie Gliniak, Christy M. Gordillo, Ruth Smith, Gordon I. Holland, William L. Gupta, Rana K. Dong, Bingning Caron, Nathalie Xu, Yong Akgul, Yucel Klein, Samuel Scherer, Philipp E. Nat Commun Article Plasma hyaluronan (HA) increases systemically in type 2 diabetes (T2D) and the HA synthesis inhibitor, 4-Methylumbelliferone, has been proposed to treat the disease. However, HA is also implicated in normal physiology. Therefore, we generated a Hyaluronan Synthase 2 transgenic mouse line, driven by a tet-response element promoter to understand the role of HA in systemic metabolism. To our surprise, adipocyte-specific overproduction of HA leads to smaller adipocytes and protects mice from high-fat-high-sucrose-diet-induced obesity and glucose intolerance. Adipocytes also have more free glycerol that can be released upon beta3 adrenergic stimulation. Improvements in glucose tolerance were not linked to increased plasma HA. Instead, an HA-driven systemic substrate redistribution and adipose tissue-liver crosstalk contributes to the systemic glucose improvements. In summary, we demonstrate an unexpected improvement in glucose metabolism as a consequence of HA overproduction in adipose tissue, which argues against the use of systemic HA synthesis inhibitors to treat obesity and T2D. Nature Publishing Group UK 2021-08-10 /pmc/articles/PMC8355239/ /pubmed/34376643 http://dx.doi.org/10.1038/s41467-021-25025-4 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zhu, Yi
Li, Na
Huang, Mingyang
Bartels, Mason
Dogné, Sophie
Zhao, Shangang
Chen, Xi
Crewe, Clair
Straub, Leon
Vishvanath, Lavanya
Zhang, Zhuzhen
Shao, Mengle
Yang, Yongjie
Gliniak, Christy M.
Gordillo, Ruth
Smith, Gordon I.
Holland, William L.
Gupta, Rana K.
Dong, Bingning
Caron, Nathalie
Xu, Yong
Akgul, Yucel
Klein, Samuel
Scherer, Philipp E.
Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
title Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
title_full Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
title_fullStr Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
title_full_unstemmed Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
title_short Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
title_sort adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for cl 316,243-stimulated lipolysis
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8355239/
https://www.ncbi.nlm.nih.gov/pubmed/34376643
http://dx.doi.org/10.1038/s41467-021-25025-4
work_keys_str_mv AT zhuyi adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT lina adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT huangmingyang adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT bartelsmason adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT dognesophie adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT zhaoshangang adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT chenxi adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT creweclair adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT straubleon adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT vishvanathlavanya adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT zhangzhuzhen adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT shaomengle adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT yangyongjie adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT gliniakchristym adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT gordilloruth adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT smithgordoni adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT hollandwilliaml adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT guptaranak adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT dongbingning adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT caronnathalie adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT xuyong adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT akgulyucel adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT kleinsamuel adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis
AT schererphilippe adiposetissuehyaluronanproductionimprovessystemicglucosehomeostasisandprimesadipocytesforcl316243stimulatedlipolysis