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

Journal Article (Journal 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.

Full Text

Duke Authors

Cited Authors

  • Zhu, Y; Li, N; Huang, M; Bartels, M; Dogné, S; Zhao, S; Chen, X; Crewe, C; Straub, L; Vishvanath, L; Zhang, Z; Shao, M; Yang, Y; Gliniak, CM; Gordillo, R; Smith, GI; Holland, WL; Gupta, RK; Dong, B; Caron, N; Xu, Y; Akgul, Y; Klein, S; Scherer, PE

Published Date

  • August 10, 2021

Published In

Volume / Issue

  • 12 / 1

Start / End Page

  • 4829 -

PubMed ID

  • 34376643

Pubmed Central ID

  • PMC8355239

Electronic International Standard Serial Number (EISSN)

  • 2041-1723

Digital Object Identifier (DOI)

  • 10.1038/s41467-021-25025-4


  • eng

Conference Location

  • England