Inductive effect of high fat diet on uncoupling protein 2 in rats with nonalcoholic fatty liver

Xiaohong GU; Yundong ZHANG; Aijuan FENG

ABSTRACT

BACKGROUND:

Up to now the pathogenesy of nonalcoholic fatty liver(NAFL) is unclear. Uncoupling protein (UCP) of mitochondrial membrane can make oxidative phosphorylation uncoupling in mitochondrium, and then result in decreasing the efficiency of ATP synthesis by mitochondrium and participate the progression of fatty liver by changing energy metabolism.

OBJECTIVE:

To observe the expressive rule of UCP-2 in NAFL rat models at different time phases.

DESIGN:

Randomized control animal trial.

SETTING:

Department of Gastroenterology, Research Institute of Surgery,Daping Hospital, Third Military Medical University of Chinese PLA.MATERIALS The experiment was performed at National Key Laboratory,Research Institute of Surgery, Daping Hospital, Third Military Medical University of Chinese PLA from November 2004 to December 2005. A total of 64 clean-grade Wistar adult male rats were selected. After being fed with common feed for 1 week, the rats were randomly assigned into model group and normal control group with 32 rats in each group. In each group there were 4 time points feeding for 2, 4, 8 and 12 weeks, 8 ones at each time point.

METHODS:

The rats in model group received high fat diet (88% basic feed, 10% pork fat and 2% cholesterol) for 12 weeks. Those in normal control group received common feed in different cages (6 rats in each cage).MAIN OUTCOME

MEASURES:

Blood was collected from anesthetic rats of the two groups at corresponding time point. Animals were killed,and then liver was extracted rapidly. ①Change of expression of UCP-2in liver was determined with immunohistochemical method and Western blot technique. ②Activity of triacylglycerol, free fatty acid (FFA) and alanine aminotransferase (ALT) in serum was measured with biochemical method. ③Content of malondialdehyde (MDA) in liver tissues was measured.

RESULTS:

Totally 64 rats were involved in the result analysis. ①Biochemical indicators in serum Levels of triacylglycerol, FFA and ALT in serum were significantly higher in the model group than in the normal control group at weeks 4, 8 and 12, especially at weeks 8 and 12 (P ＜ 0.01). ②The expression of UCP-2 enhanced gradually with the exacerbation of fatt yliver in the model group, while it was negative in the normal control group.③Content of MDA in liver tissues It was significantly higher in the model group than in the normal control group at weeks 4, 8 and 12, especially at weeks 8 and 12 [(4.07±0.15), (4.93±0.14), (5.20±0.20) μmol/g; (3.14±0.20), (3.12±0.18), (3.13±0.16) μmol/g,P ＜ 0.01].

CONCLUSION:

With the formation and aggravation of nonalcoholic fatty liver, levels of triacylglycerol, FFA and ALT in serum and content of MDA in liver tissues increase, and the expression of UCP-2 also increase. It is indicated that high fat diet can induce expression of hepatocyte UCP-2,decrease of ATP progression in cells and accelerate the formation and development of fatty liver.