E4orf1 Improves Lipid and Glucose Metabolism in Hepatocytes: A Template to Improve Steatosis & Hyperglycemia

Emily J. Dhurandhar, Rashmi Krishnapuram, Vijay Hegde, Olga Dubuisson, Rongya Tao, X. Dong, Jianping Ye, Nikhil V. Dhurandhar

Research output: Contribution to journalArticle

21 Citations (Scopus)

Abstract

Hepatic steatosis often accompanies obesity and insulin resistance. The cornerstones of steatosis treatment include reducing body weight and dietary fat intake, which are marginally successful over the long term. Ad36, a human adenovirus, may offer a template to overcome these limitations. In vitro and in vivo studies collectively indicate that via its E4orf1 protein, Ad36 improves hyperglycemia, and attenuates hepatic steatosis, despite a high fat diet and without weight loss. Considering that hepatic insulin sensitivity, or the synthesis, oxidation, or export of fatty acid by hepatocytes are the key determinant of hepatic lipid storage, we determined the role of E4orf1 protein in modulating these physiological pathways. For this study, HepG2 cells, or mouse primary hepatocytes were transfected with E4orf1 or the null vector. Glucose output by hepatocytes was determined under gluconeogenic conditions (cAMP and dexamethasone, or glucagon exposure). Also, de-novo lipogenesis, palmitate oxidation, and lipid export as determined by apoB secretion were measured 48 h post transfection. Results show that compared to null vector transfected cells, E4orf1 significantly reduced glucose output in basal and gluconeogenic conditions. E4orf1 reduced de-novo lipogenesis by about 35%, increased complete fatty acid oxidation 2-fold (p<0.0001), and apoB secretion 1.5 fold(p<0.003). Response of key signaling molecules to E4orf1 transfection was in agreement with these findings. Thus, E4orf1 offers a valuable template to exogenously modulate hepatic glucose and lipid metabolism. Elucidating the underlying molecular mechanism may help develop therapeutic approaches for treating diabetes or non-alcoholic fatty liver disease(NAFLD).

Original languageEnglish
Article numbere47813
JournalPLoS One
Volume7
Issue number10
DOIs
StatePublished - Oct 23 2012

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fatty liver
hyperglycemia
Lipid Metabolism
Metabolism
Hyperglycemia
hepatocytes
Hepatocytes
lipogenesis
Apolipoproteins B
transfection
Lipids
Glucose
insulin resistance
Oxidation
liver
glucose
metabolism
Liver
Fatty Acids
lipids

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Dhurandhar, E. J., Krishnapuram, R., Hegde, V., Dubuisson, O., Tao, R., Dong, X., ... Dhurandhar, N. V. (2012). E4orf1 Improves Lipid and Glucose Metabolism in Hepatocytes: A Template to Improve Steatosis & Hyperglycemia. PLoS One, 7(10), [e47813]. https://doi.org/10.1371/journal.pone.0047813

E4orf1 Improves Lipid and Glucose Metabolism in Hepatocytes : A Template to Improve Steatosis & Hyperglycemia. / Dhurandhar, Emily J.; Krishnapuram, Rashmi; Hegde, Vijay; Dubuisson, Olga; Tao, Rongya; Dong, X.; Ye, Jianping; Dhurandhar, Nikhil V.

In: PLoS One, Vol. 7, No. 10, e47813, 23.10.2012.

Research output: Contribution to journalArticle

Dhurandhar, EJ, Krishnapuram, R, Hegde, V, Dubuisson, O, Tao, R, Dong, X, Ye, J & Dhurandhar, NV 2012, 'E4orf1 Improves Lipid and Glucose Metabolism in Hepatocytes: A Template to Improve Steatosis & Hyperglycemia', PLoS One, vol. 7, no. 10, e47813. https://doi.org/10.1371/journal.pone.0047813
Dhurandhar, Emily J. ; Krishnapuram, Rashmi ; Hegde, Vijay ; Dubuisson, Olga ; Tao, Rongya ; Dong, X. ; Ye, Jianping ; Dhurandhar, Nikhil V. / E4orf1 Improves Lipid and Glucose Metabolism in Hepatocytes : A Template to Improve Steatosis & Hyperglycemia. In: PLoS One. 2012 ; Vol. 7, No. 10.
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