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

Publication ,  Journal Article
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 ...
Published in: Nat Commun
August 10, 2021

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.

Duke Scholars

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Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 10, 2021

Volume

12

Issue

1

Start / End Page

4829

Location

England

Related Subject Headings

  • Obesity
  • Mice, Transgenic
  • Mice
  • Male
  • Lipolysis
  • Hypoglycemic Agents
  • Hyaluronic Acid
  • Humans
  • Homeostasis
  • Glucose Intolerance
 

Citation

APA
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Zhu, Y., Li, N., Huang, M., Bartels, M., Dogné, S., Zhao, S., … Scherer, P. E. (2021). Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis. Nat Commun, 12(1), 4829. https://doi.org/10.1038/s41467-021-25025-4
Zhu, Yi, Na Li, Mingyang Huang, Mason Bartels, Sophie Dogné, Shangang Zhao, Xi Chen, et al. “Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis.Nat Commun 12, no. 1 (August 10, 2021): 4829. https://doi.org/10.1038/s41467-021-25025-4.
Zhu Y, Li N, Huang M, Bartels M, Dogné S, Zhao S, et al. Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis. Nat Commun. 2021 Aug 10;12(1):4829.
Zhu, Yi, et al. “Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis.Nat Commun, vol. 12, no. 1, Aug. 2021, p. 4829. Pubmed, doi:10.1038/s41467-021-25025-4.
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. Adipose tissue hyaluronan production improves systemic glucose homeostasis and primes adipocytes for CL 316,243-stimulated lipolysis. Nat Commun. 2021 Aug 10;12(1):4829.

Published In

Nat Commun

DOI

EISSN

2041-1723

Publication Date

August 10, 2021

Volume

12

Issue

1

Start / End Page

4829

Location

England

Related Subject Headings

  • Obesity
  • Mice, Transgenic
  • Mice
  • Male
  • Lipolysis
  • Hypoglycemic Agents
  • Hyaluronic Acid
  • Humans
  • Homeostasis
  • Glucose Intolerance