Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis
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Published:2021-08-10
Issue:1
Volume:12
Page:
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ISSN:2041-1723
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Container-title:Nature Communications
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language:en
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Short-container-title:Nat Commun
Author:
Zhu Yi, Li Na, Huang Mingyang, Bartels Mason, Dogné SophieORCID, Zhao ShangangORCID, Chen Xi, Crewe Clair, Straub LeonORCID, Vishvanath Lavanya, Zhang Zhuzhen, Shao MengleORCID, Yang Yongjie, Gliniak Christy M.ORCID, Gordillo Ruth, Smith Gordon I., Holland William L.ORCID, Gupta Rana K.ORCID, Dong Bingning, Caron Nathalie, Xu YongORCID, Akgul Yucel, Klein Samuel, Scherer Philipp E.ORCID
Abstract
AbstractPlasma 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.
Publisher
Springer Science and Business Media LLC
Subject
General Physics and Astronomy,General Biochemistry, Genetics and Molecular Biology,General Chemistry
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