Chylomicron and apoB48 metabolism in the JCR:LA corpulent rat, a model for the metabolic syndrome.
Postprandial (PP) lipaemia is a significant contributor to the development of dyslipidaemia and cardiovascular disease (CVD). It is also evident that PP lipaemia is prevalent during conditions of obesity and insulin resistance (IR) and may contribute to increased progression of CVD. Our group has assessed the potential of the obese JCR:LA-cp rat as a model of PP lipaemia in order to explore CM (chylomicron) metabolism during the onset and development of IR in the metabolic syndrome. Studies confirm that both fasting plasma and PP apoB48 (apolipoprotein B48) area under the curve are significantly elevated in the obese JCR:LA-cp phenotype as compared with lean controls. Mechanistic studies have also shown that the concentration of lymphatic CM apoB48 and CM size are significantly increased in this model. Furthermore, PP dyslipidaemia in the obese rat can be improved acutely with supplementation of n-3 polyunsaturated fatty acids. Using a different approach, we have subsequently hypothesized that the vascular remodelling that accompanies IR may explain accelerated entrapment of apoB48-containing particles. Small leucine-rich proteoglycans (including biglycan and decorin) have been observed to co-localize with apoB in human tissue. However, the potential impact of IR on vascular remodelling, particularly in the presence of obesity, remains unclear. Preliminary observations from the JCR:LA-cp model indicate that biglycan protein core content increases with age and is exacerbated by IR, suggestive of pro-atherogenic remodelling. The focus of this review is to contribute to the perspective of PP lipaemia in CVD risk associated with the metabolic syndrome through the use of animal models.
Mangat
R
R
Metabolic and Cardiovascular Diseases Laboratory, Alberta Institute for Human Nutrition, University of Alberta, Edmonton, AB, Canada, T6G 2PS.
Su
J
J
Scott
P G
PG
Russell
J C
JC
Vine
D F
DF
Proctor
S D
SD
D000818:Animals; D053283:Apolipoprotein B-48 / Q000378:metabolism*; D050197:Atherosclerosis / Q000209:etiology / Q000378:metabolism; D002914:Chylomicrons / Q000378:metabolism*; D004195:Disease Models, Animal; D015525:Fatty Acids, Omega-3 / Q000494:pharmacology; D006801:Humans; D006949:Hyperlipidemias / Q000188:drug therapy / Q000378:metabolism; D015228:Hypertriglyceridemia / Q000378:metabolism; D007328:Insulin / Q000378:metabolism; D007333:Insulin Resistance; D007413:Intestinal Mucosa / Q000378:metabolism; D008079:Lipoproteins, VLDL / Q000378:metabolism; D024821:Metabolic Syndrome / Q000150:complications / Q000378:metabolism*; D051381:Rats; D011922:Rats, Mutant Strains
D053283:Apolipoprotein B-48; D002914:Chylomicrons; D015525:Fatty Acids, Omega-3; D007328:Insulin; D008079:Lipoproteins, VLDL