Apolipoprotein AV does not contribute to hypertriglyceridaemia or triglyceride lowering by dietary fish oil and rosiglitazone in obese Zucker rats.
OBJECTIVE
Apolipoprotein AV (apoAV) is a recently discovered apolipoprotein with a triglyceride-lowering effect in genetically modified mice. Transcription of the human gene encoding apoAV (APOA5) is suppressed by insulin and stimulated by fibrates. Our goal was to study the expression of Apoa5, in comparison with Apoa4 and Apoc3, in hypertriglyceridaemic, obese and insulin-resistant Zucker rats receiving the insulin sensitiser rosiglitazone and/or a fish oil diet to lower triglycerides.


METHODS
Hepatic Apoa5, Apoa4 and Apo3 mRNA and liver and plasma apoAV were measured in lean and obese Zucker rats receiving rosiglitazone while on a coconut oil or fish oil diet.


RESULTS
Basal hepatic Apoa5 expression was similar in obese and lean Zucker rats. Unexpectedly, obese Zucker rats tended to have higher plasma apoAV levels despite their hypertriglyceridaemic state. Both rosiglitazone and the fish oil diet significantly increased Apoa5 mRNA, by about 70%, but tended to lower liver and plasma apoAV. Rosiglitazone had no effect on Apoa5 mRNA in cultured rat hepatocytes. No intact PPAR (peroxisome proliferator-activated receptor) response element was identified in the rat Apoa5 promoter.


CONCLUSIONS
Our data indicate that apoAV does not contribute to the hypertriglyceridaemia of obese Zucker rats or to the hypolipidaemic effect of rosiglitazone or a fish oil diet. The divergent changes of Apoa5 mRNA and apoAV levels suggest co- or post-translational regulation. The increase in Apoa5 mRNA induced by rosiglitazone is not directly mediated by peroxisome proliferator-activated receptor gamma.
Department of Medical Chemistry, Center of Physiology and Pathophysiology, Medical University of Vienna, Währinger Strasse 9, A-1090 Vienna, Austria.
B
B
Dorfmeister
S
S
Brandlhofer
F G
FG
Schaap
M
M
Hermann
C
C
Fürnsinn
B P
BP
Hagerty
H
H
Stangl
W
W
Patsch
W
W
Strobl
D000818:Animals; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins / Q000235:genetics*; D001483:Base Sequence; D002784:Cholesterol / Q000097:blood; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3 / Q000627:therapeutic use*; D005395:Fish Oils / Q000627:therapeutic use*; D015228:Hypertriglyceridemia / Q000097:blood* / Q000188:drug therapy; D007328:Insulin / Q000097:blood; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics*; D047495:PPAR gamma; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats; D011924:Rats, Zucker; D000077154:Rosiglitazone; D016415:Sequence Alignment; D012689:Sequence Homology, Nucleic Acid; D045162:Thiazolidinediones / Q000627:therapeutic use*; D014280:Triglycerides / Q000097:blood*
C514818:Apoa5 protein, rat; D000072040:Apolipoprotein A-V; D001053:Apolipoproteins; D004041:Dietary Fats; D005230:Fatty Acids, Nonesterified; D015525:Fatty Acids, Omega-3; D005395:Fish Oils; D007328:Insulin; D047495:PPAR gamma; D012333:RNA, Messenger; D045162:Thiazolidinediones; D014280:Triglycerides; D000077154:Rosiglitazone; D002784:Cholesterol