Impaired postprandial apolipoprotein-B48 metabolism in the obese, insulin-resistant JCR:LA-cp rat: increased atherogenicity for the metabolic syndrome.
OBJECTIVE
Postprandial lipaemia is a significant contributor to the development of dyslipidaemia and cardiovascular disease, which has more recently been shown as a potential risk factor for obesity and pre-diabetes. Clinically however, the diagnosis of early insulin-resistance remains confounded due to the fact that aberrations in lipid metabolism are not often readily identified using classic indicators of hypercholesterolemia (i.e. LDL).


METHODS
In this study, we assessed the metabolism of apolipoprotein-B48 (apoB48)-containing lipoproteins in an animal model of obesity and insulin-resistance, the JCR:LA-cp rat. The contribution of lipoproteins from the intestine was assessed by measuring plasma apoB48 concentration in the postprandial period following an oral fat load. Plasma apoB48 was measured by improved enhanced chemiluminescent detection and other biochemical parameters measured by established analysis.


RESULTS
Fasting concentrations of plasma apoB48, postprandial apoB48 area under the curve (AUC), as well as incremental-AUC (iAUC), were all significantly greater in the obese phenotype compared to lean controls. Fasting apoB48 correlated significantly with apoB48-iAUC, triglyceride (TG)-iAUC and insulin-iAUC. In addition, there was a highly significant association with fasting insulin and the postprandial ratio of TG:apoB48, a relationship not often detected in humans during insulin-resistance.


CONCLUSIONS
We conclude that the JCR:LA-cp rat can be used as a model of postprandial lipemia to explore chylomicron metabolism during the onset and development of insulin-resistance, including the increased cardiovascular complications of the metabolic syndrome.
Vine
D F
DF
Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, University of Alberta, Edmonton, Alta, Canada.
Takechi
R
R
Russell
J C
JC
Proctor
S D
SD
D000818:Animals; D053283:Apolipoprotein B-48 / Q000097:blood*; D050197:Atherosclerosis / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D002914:Chylomicrons / Q000097:blood; D004195:Disease Models, Animal; D006946:Hyperinsulinism / Q000097:blood; D007333:Insulin Resistance; D008074:Lipoproteins / Q000097:blood; D008297:Male; D024821:Metabolic Syndrome / Q000097:blood*; D009765:Obesity / Q000097:blood*; D019518:Postprandial Period; D051381:Rats; D011919:Rats, Inbred Strains; D014280:Triglycerides / Q000097:blood
D053283:Apolipoprotein B-48; D015415:Biomarkers; D002914:Chylomicrons; D008074:Lipoproteins; D014280:Triglycerides