Bile duct obstruction is associated with early postoperative upregulation of liver uncoupling protein-2 and reduced circulating glucose concentration in the rat

Enochsson, Lars; Isaksson, Bengt; Strömmer, Lovisa; Erlanson-Albertsson, Charlotte; Permert, Johan

doi:10.1016/j.nut.2009.05.005

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Volume 26, Issue 4 , Pages 405-410, April 2010

Bile duct obstruction is associated with early postoperative upregulation of liver uncoupling protein-2 and reduced circulating glucose concentration in the rat

Lars Enochsson, M.D., Ph.D.
- Division of Surgery, Department for Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet at Karolinska University Hospital–Huddinge, Stockholm, Sweden
- Corresponding author. Tel.: +46-8-5858-0000; fax: +46-8-5858-2340.
Bengt Isaksson, M.D., Ph.D.
- Division of Surgery, Department for Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet at Karolinska University Hospital–Huddinge, Stockholm, Sweden
Lovisa Strömmer, M.D., Ph.D.
- Division of Surgery, Department for Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet at Karolinska University Hospital–Huddinge, Stockholm, Sweden
Charlotte Erlanson-Albertsson, M.D., Ph.D.
- Department of Cell and Molecular Biology, Biomedical Center (BMC), University of Lund, Lund, Sweden
Johan Permert, M.D., Ph.D.
- Division of Surgery, Department for Clinical Science Intervention and Technology (CLINTEC), Karolinska Institutet at Karolinska University Hospital–Huddinge, Stockholm, Sweden

Received 9 October 2008; accepted 14 May 2009. published online 27 July 2009.

Abstract

Objective

To evaluate whether upregulation of liver and muscle uncoupling protein 2 (UCP-2) is an acute phenomenon in obstructive jaundice and associated with secondary metabolic effects.

Methods

Male Sprague-Dawley rats were divided into four groups: bile duct ligated (BDL) and sham-operated pair-fed (PF), ad libitum fed (AL), and controls. BDL, PF, and AL rats were further divided into subgroups according to the interval postoperatively when they were reanesthetized and sampled for tissue and blood: 2, 4, and 8 d, respectively. Bilirubin, liver enzymes, glucose, free fatty acids, and insulin in blood plasma were analyzed. Liver and muscle tissue were sampled for UCP-2 and adenosine triphosphate analysis.

Results

The BDL rats showed an increase of the liver UCP-2 expression compared with PF and AL rats (P<0.05) 4 d postoperatively. Liver adenosine triphosphate in BDL rats showed a decrease compared with sham-operated controls at all intervals (P<0.05). Plasma glucose concentration in BDL rats was decreased compared with the other groups. Free fatty acids showed an initial increase 2 d postoperatively compared with sham-operated controls and PF and AL rats (P<0.05) at the corresponding time point.

Conclusion

Obstructive jaundice is associated with an early upregulation of liver UCP-2, reduced liver adenosine triphosphate content, and decreased plasma glucose concentration, supporting the hypothesis that obstructive jaundice results in impaired energy homeostasis in the liver, which might cause decreased glucose output and hypoglycemia as a consequence.

Keywords: Bile duct ligation, Mitochondria, Obstructive jaundice, Uncoupling protein