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Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia.

Publication ,  Journal Article
Waskowicz, LR; Zhou, J; Landau, DJ; Brooks, ED; Lim, A; Yavarow, ZA; Kudo, T; Zhang, H; Wu, Y; Grant, S; Young, SP; Huat, BB; Yen, PM; Koeberl, DD
Published in: Hum Mol Genet
January 1, 2019

Glucose-6-phosphatase α (G6Pase) deficiency, also known as von Gierke's Disease or Glycogen storage disease type Ia (GSD Ia), is characterized by decreased ability of the liver to convert glucose-6-phosphate to glucose leading to glycogen accumulation and hepatosteatosis. Long-term complications of GSD Ia include hepatic adenomas and carcinomas, in association with the suppression of autophagy in the liver. The G6pc-/- mouse and canine models for GSD Ia were treated with the pan-peroxisomal proliferator-activated receptor agonist, bezafibrate, to determine the drug's effect on liver metabolism and function. Hepatic glycogen and triglyceride concentrations were measured and western blotting was performed to investigate pathways affected by the treatment. Bezafibrate decreased liver triglyceride and glycogen concentrations and partially reversed the autophagy defect previously demonstrated in GSD Ia models. Changes in medium-chain acyl-CoA dehydrogenase expression and acylcarnintine flux suggested that fatty acid oxidation was increased and fatty acid synthase expression associated with lipogenesis was decreased in G6pc-/- mice treated with bezafibrate. In summary, bezafibrate induced autophagy in the liver while increasing fatty acid oxidation and decreasing lipogenesis in G6pc-/- mice. It represents a potential therapy for glycogen overload and hepatosteatosis associated with GSD Ia, with beneficial effects that have implications for non-alcoholic fatty liver disease.

Duke Scholars

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

January 1, 2019

Volume

28

Issue

1

Start / End Page

143 / 154

Location

England

Related Subject Headings

  • Triglycerides
  • Mice, Knockout
  • Mice
  • Liver
  • Lipid Metabolism
  • Glycogen Storage Disease Type I
  • Glycogen
  • Glucose-6-Phosphate
  • Glucose-6-Phosphatase
  • Glucose
 

Citation

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MLA
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Waskowicz, L. R., Zhou, J., Landau, D. J., Brooks, E. D., Lim, A., Yavarow, Z. A., … Koeberl, D. D. (2019). Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia. Hum Mol Genet, 28(1), 143–154. https://doi.org/10.1093/hmg/ddy343
Waskowicz, Lauren R., Jin Zhou, Dustin J. Landau, Elizabeth D. Brooks, Andrea Lim, Zollie A. Yavarow, Tsubasa Kudo, et al. “Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia.Hum Mol Genet 28, no. 1 (January 1, 2019): 143–54. https://doi.org/10.1093/hmg/ddy343.
Waskowicz LR, Zhou J, Landau DJ, Brooks ED, Lim A, Yavarow ZA, et al. Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia. Hum Mol Genet. 2019 Jan 1;28(1):143–54.
Waskowicz, Lauren R., et al. “Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia.Hum Mol Genet, vol. 28, no. 1, Jan. 2019, pp. 143–54. Pubmed, doi:10.1093/hmg/ddy343.
Waskowicz LR, Zhou J, Landau DJ, Brooks ED, Lim A, Yavarow ZA, Kudo T, Zhang H, Wu Y, Grant S, Young SP, Huat BB, Yen PM, Koeberl DD. Bezafibrate induces autophagy and improves hepatic lipid metabolism in glycogen storage disease type Ia. Hum Mol Genet. 2019 Jan 1;28(1):143–154.
Journal cover image

Published In

Hum Mol Genet

DOI

EISSN

1460-2083

Publication Date

January 1, 2019

Volume

28

Issue

1

Start / End Page

143 / 154

Location

England

Related Subject Headings

  • Triglycerides
  • Mice, Knockout
  • Mice
  • Liver
  • Lipid Metabolism
  • Glycogen Storage Disease Type I
  • Glycogen
  • Glucose-6-Phosphate
  • Glucose-6-Phosphatase
  • Glucose