[Inflammation enhances the accumulation of lipid in ApoE/SRA/CD36 KO mice liver].
OBJECTIVE
To investigate if inflammatory stress enhances liver lipid accumulation via SREBPs mediated dysregulation of low density protein receptor (LDLr) expression in apolipoprotein E, scavenger receptors class A and CD36 triple knockout (ApoE/SRA/CD36 KO) mice.


METHODS
16 Male ApoE/SRA/CD36 KO mice were subcutaneously injected with 0.5 ml 10% casein or PBS. The mice were fed a Western diet (Harlan, TD88137) containing 21% fat and 0.15% of cholesterol for 14 weeks. Animals were sacrificed and blood samples were collected. The serum amyloid A (SAA), IL-6, total cholesterol (TC), LDL and high density protein (HDL) were assayed. The lipid accumulation in liver was evaluated by Oil Red O staining. The mRNA and protein expression of SREBP-2, SREBPs cleavage activating protein (SCAP) and LDLr were analyzed by Real-Time Polymerase Chain Reaction (RT-PCR) and immunohistochemistry staining.


RESULTS
Blood levels of SAA [(26.60+/-3.24) ng/ml vs (14.35+/-1.73) ng/ml, P < 0.01] and IL-6 [(36.37+/-2.20) pg/ml vs (18.02+/-4.87) pg/ml, P < 0.01] were higher, while TC [(7.72+/-1.70) mmol/L vs (13.23+/-3.61)mmol/L, P less than 0.01], LDL-cholesterol [(2.94+/-0.44) mmol/L vs (9.28+/-3.66) mmol/L, P less than 0.01] and HDL cholesterol [(2.24+/-0.63) mmol/L vs (4.13+/-0.42) mmol/L, P less than 0.01] were lower in inflamed mice compared to controls. ORO staining showed that lipid accumulation in the liver was more extensive in inflamed group despite lower blood lipid levels. Meanwhile, Real Time PCR data showed inflammation induced the expression of LDLr (4.56 fold), SCAP (3.14 fold) and SREBP-2 (14.72 fold) in liver. Immunohistochemical staining also indicated increased proteins expression in the liver, which was consistent with mRNA data.


CONCLUSIONS
Inflammation causes lipid accumulation in liver via disrupting SREBP-2 and LDLr expression.
Yan
Feng
F
Center for Lipid Research, Key Laboratory of Molecular Biology on Infectious Diseases, Ministry of Education, Second Affiliated Hospital, Chongqing Medical University, Chongqing 400016, China.
Huang
Ai-long
AL
Xu
Zhen-e
ZE
Ruan
Xiong-zhong
XZ
Chen
Ya-xi
YX
D000818:Animals; D001057:Apolipoproteins E / Q000235:genetics; D008078:Cholesterol, LDL / Q000378:metabolism; D005234:Fatty Liver / Q000378:metabolism*; D007249:Inflammation / Q000378:metabolism; D008099:Liver / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D011973:Receptors, LDL / Q000378:metabolism*; D051782:Sterol Regulatory Element Binding Protein 2 / Q000378:metabolism*
D001057:Apolipoproteins E; D008078:Cholesterol, LDL; D011973:Receptors, LDL; C497391:Srebf2 protein, mouse; D051782:Sterol Regulatory Element Binding Protein 2