Increased apolipoprotein A5 expression in human and rat non-alcoholic fatty livers.
Apolipoprotein A5 (apoA5) is a potent regulator of triglyceride (TG) metabolism and therefore may contribute to the pathogenesis of non-alcoholic fatty liver disease (NAFLD), a disease characterised by excessive TG-rich lipid droplets in hepatocytes. To test this hypothesis, we examined the mRNA expression of apoA5 in paediatric NAFLD livers in comparison to healthy controls. According to microarray and quantitative real-time PCR, human NAFLD livers exhibited elevated apoA5 expression compared to healthy controls. The apoA5 expression levels were positively correlated with hepatic TG storage and a marker for lipid droplets (perilipin), but were not correlated with plasma TG levels. These observations were confirmed with a NAFLD rat model. Interestingly, apoA5 expression was not altered in cultured fat-laden HepG2 cells, demonstrating that fat storage does not induce apoA5 in NAFLD livers. Therefore, the correlation between apoA5 and intracellular fat storage is likely explained by the potent effect of apoA5 in promoting intracellular fat storage. Our NAFLD patients and rats had elevated insulin resistance, which may have a role in elevating apoA5 expression in NAFLD livers. Our data support the hypothesis that apoA5 promotes hepatic TG storage and therefore contributes to the pathogenesis of NAFLD, and may represent a potential target for therapeutic intervention.
1Institute of Hepatology, Shuguang Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China 2Digestive Diseases and Nutrition Center, Women and Children's Hospital of Buffalo, Department of Pediatrics, the State University of New York at Buffalo, Buffalo, NY 3Center for Prevention of Obesity, Diabetes and Cardiovascular Disease, Children's Hospital Oakland Research Institute, Oakland, CA, United States 4Institute of Digestive Diseases, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai, China *these senior authors contributed equally to this work.
Qin
Q
Feng
Susan S
SS
Baker
Wensheng
W
Liu
Ricardo A
RA
Arbizu
Ghanim
G
Aljomah
Maan
M
Khatib
Colleen A
CA
Nugent
Robert D
RD
Baker
Trudy M
TM
Forte
Yiyang
Y
Hu
Lixin
L
Zhu
D000293:Adolescent; D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000096:biosynthesis; D001054:Apolipoproteins A / Q000096:biosynthesis*; D015153:Blotting, Western; D002648:Child; D005260:Female; D056945:Hep G2 Cells; D006801:Humans; D008297:Male; D065626:Non-alcoholic Fatty Liver Disease / Q000378:metabolism* / Q000473:pathology; D020411:Oligonucleotide Array Sequence Analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D060888:Real-Time Polymerase Chain Reaction
C437704:APOA5 protein, human; C514818:Apoa5 protein, rat; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D001054:Apolipoproteins A