Chylomicron and apoB48 metabolism in the JCR:LA corpulent rat, a model for the metabolic syndrome

Abstract

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.

The small leucine-rich proteoglycan, biglycan, is highly expressed in adipose tissue of Psammomys obesus and is associated with obesity and type 2 diabetes

“…Recent studies have demonstrated biglycan to be upregulated in a murine model of diet-induced obesity with atherosclerosis,23 to be involved in vascular and proatherogenic remodeling in a rat model of metabolic syndrome,24 to be proangiogenic,25 and interestingly, to have upregulated expression in parallel with matrix degradation genes in white adipose tissue from db/db mice fed a high fat diet 2026.…”

Streptococcus pneumoniae worsens cerebral ischemia via interleukin 1 and platelet glycoprotein Ibα

“…Male Wistar rats were 8 weeks old (250-300g). Aged (15 months) lean and (JCR:LA-cp; cp/cp) corpulent rats, which are obese, atherosclerotic, and insulin resistant, 15 were also used. Animals were allowed free access to food and water and maintained under temperature-, humidity-, and light-controlled conditions.…”

“…Corpulent rats that spontaneously develop atherosclerosis as they age 15 were fed a chow diet throughout. Mice and rats were sacrificed 6 or 7 days after the first infection, respectively.…”

Elevation of tumor necrosis factor-α induces the overproduction of postprandial intestinal apolipoprotein B48-containing very low-density lipoprotein particles: evidence for related gene expression of inflammatory, insulin and lipoprotein signaling in enterocytes

“…9,10 It secretes VLDLs and chylomicrons to transport fat and fat-soluble vitamins into the blood. Studies 10,11 confirm that both fasting and postprandial intestinal apoB48 are significantly elevated during conditions of obesity and insulin resistance. The accumulation of apoB48-containing particles in the insulin-resistant state may be an important contributor to the elevation of circulating triglyceride-rich lipoproteins (TRL)s, 10,12 which are particularly atherogenic.…”