Impaired postprandial apolipoprotein-B48 metabolism in the obese, insulin-resistant JCR:LA-cp rat: Increased atherogenicity for the metabolic syndrome

Vine, Donna F.; Takechi, Ryusuke; Russell, James B.; Proctor, Spencer D.

doi:10.1016/j.atherosclerosis.2006.03.013

Cited by 83 publications

(87 citation statements)

References 43 publications

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“…Hormonal secretion is rapidly modulated in the fasted-to-fed that developed obesity and IR showed signifi cantly higher rates of de novo TG synthesis, apoB-48, and TRLs, suggesting that IR induces an oversecretion of intestinal apoB-48-containing lipoproteins in these animals. Similarly, Vine et al ( 33 ) reported impaired postprandial apoB-48 metabolism, greater TG absorption, and higher levels of apoB-48 in the lymph of obese IR JCR:LA-cp rats. Studies have also revealed abnormal intestinal lipoprotein metabolism in Zucker diabetic fatty rats.…”

Section: Intestinal Protein Levels Assessed By Lc-ms/msmentioning

confidence: 84%

Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance

Couture

Tremblay

Kelly

et al. 2014

Journal of Lipid Research

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Dyslipidemia is an important feature of insulin resistance (IR) that contributes to the pathogenesis of atherosclerosis and increases the risk of cardiovascular disease ( 1 ). Dyslipidemia associated with IR is typically characterized by elevated concentrations of triglyceride-rich lipoproteins (TRLs), reduced plasma levels of HDL-cholesterol (HDL-C), an increased number of small dense LDL particles, and greater levels of free fatty acid (FFA) ( 1 ). Metabolic kinetic studies have indicated that the increased plasma levels of TRLs in individuals with IR are caused by the elevated secretion of both hepatic (apoB-100-containing) and intestinal (apoB-48-containing) lipoproteins in fasting and postprandial states ( 2-5 ). We have already shown that the intestinal lipoprotein production rate (PR) is markedly greater in dyslipidemic patients with type 2 diabetes ( 6 ). This relationship is of signifi cant interest because there is now convincing evidence indicating that elevated levels of intestine-derived lipoproteins are proatherogenic and associated with an increased risk of cardiovascular disease ( 7-9 ). Hence, a better understanding of the factors regulating intestinal lipoprotein secretion could potentially lead to rational therapeutic strategies to reduce cardiovascular risk in this vulnerable group of patients. Abstract Insulin resistance (IR) is

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Section: Intestinal Protein Levels Assessed By Lc-ms/msmentioning

confidence: 84%

Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance

Couture

Tremblay

Kelly

et al. 2014

Journal of Lipid Research

View full text Add to dashboard Cite

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“…After 8 weeks of feeding and exercise intervention, a standardized meal tolerance test (MTT) was performed. Briefly, animals were fasted overnight and given a 5.0 g chow meal pellet, and blood was taken using an established tail-snip procedure (Vine et al 2007). …”

Section: Exercise and Energy-restriction Diet Protocolmentioning

confidence: 99%

“…The free androgen index (FAI) was calculated (FAIZ100; total testosterone/SHBG) (Azziz et al 2009). Apolipoproteins (apo) B48 (a marker of intestinal chylomicron (CM)) and B100 (a marker of hepatic VLDL and LDL) were quantified in fasting plasma using a western blotting procedure, SDS-PAGE combined with ECL analysis, as described previously (Vine et al 2007). …”

Section: Plasma Biochemical Analysesmentioning

confidence: 99%

Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model

Diané

Kupreeva

Borthwick

et al. 2015

Journal of Endocrinology

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Polycystic ovary syndrome (PCOS) is one of the most common endocrine-metabolic disorders in women of reproductive age characterized by ovulatory dysfunction, hyperandrogenism and cardiometabolic risk. The overweight-obese PCOS phenotype appears to have exacerbated reproductive dysfunction and cardiometabolic risk. In overweight-obese adult women with PCOS, exercise and energy restricted diets have shown limited and inconsistent effects on both cardiometabolic indices and reproductive outcomes. We hypothesized that an early lifestyle intervention involving exercise and dietary energy restriction to prevent or reduce the propensity for adiposity would modulate reproductive indices and cardiometabolic risk in an obese PCOS-prone rodent model. Weanling obese PCOS-prone and Lean-Control JCR:LA-cp rodents were given a chow diet ad libitum or an energyrestricted diet combined with or without voluntary exercise (4 h/day) for 8 weeks. Dietary energy restriction and exercise lowered total body weight gain and body fat mass by 30% compared to free-fed sedentary or exercising obese PCOS-prone animals (P!0.01). Energy restriction induced an increase in exercise intensity compared to free-feeding plus exercise conditions. Energy restriction and exercise decreased fasting plasma triglycerides and apoB48 concentrations in obese PCOS-prone animals compared to free-fed and exercise or sedentary groups. The energy restriction and exercise combination in obese PCOS-prone animals significantly increased plasma sex-hormone binding globulin, hypothalamic cocaine-and amphetamine-regulated transcript (CART) and Kisspeptin mRNA expression to levels of the Lean-Control group, and this was further associated with improvements in estrous cyclicity. The combination of exercise and dietary energy restriction when initiated in early life exerts beneficial effects on cardiometabolic and reproductive indices in an obese PCOS-prone rodent model, and this may be associated with normalization of the hypothalamic neuropeptides, Kisspeptin and CART.

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“…Rats that are homozygous for the autosomal recessive cp gene (cp/cp) are obese and insulin resistant, have dyslipidaemia and develop early atherosclerotic lesions. [12][13][14] Consequently, this model has been used extensively to study the impact of metabolic syndrome on various parameters of cardiovascular disease; 15,16 however, this is the first study to examine aspects of the gut-associated immune system. It is well established that dietary nutrients, particularly lipids, can influence T-cell function and the inflammatory response.…”

Section: Introductionmentioning

confidence: 99%

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

2008

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Objective: Aberrant immune responses have been identified in obesity; however, immune cells of lymph nodes residing in the inflammatory environment of visceral adipose tissue have been largely overlooked. Eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) can reduce inflammation and modify T-cell function and therefore may improve immune function in obesity. Thus, we determined the effects of feeding fish oil (FO) containing EPA and DHA on mesenteric lymph node (MLN) immune cell function. Methods: In this study, 14-week-old obese, leptin receptor-deficient JCR:LA-cp rats (cp/cp) (n ¼ 10 per group) were randomized to one of three nutritionally adequate diets for 3 weeks: control (ctl, 0% EPA þ DHA), low FO (LFO, 0.8% w/w EPA þ DHA) or high FO (HFO, 1.4% w/w EPA þ DHA). Lean JCR:LA-cp (Cp/cp or Cp/Cp) rats (n ¼ 5) were fed ctl diet. MLN cell phospholipid (PL) fatty acid composition, phenotypes and cytokine production were measured. Results: Obese ctl rats produced more IL-1b, IL-4 and IL-10, despite a higher proportion of (nÀ3) polyunsaturated fatty acids (PUFAs) and a lower (nÀ6):(nÀ3) PUFA ratio in MLN PL compared with lean ctl rats (Po0.05). Concanavalin A-stimulated IL-2 production did not differ from lean rats even though obese ctl rats had a lower proportion of CD4 þ CD25 þ cells (Po0.05). Feeding FO to obese rats increased the incorporation of (nÀ3) PUFA into MLN PL and normalized production of IL-1b (HFO only), IL-4 and IL-10 to the levels similar to lean ctl rats (Po0.05). Conclusion: We demonstrate for the first time that obese JCR:LA-cp rats have impaired responses of MLN immune cells to mitogen stimulation and altered PL fatty acid composition. Feeding FO lowered the ex vivo inflammatory response (HFO only) and production of Th2 cytokines, without changing IL-2 production from ConA-stimulated splenocytes, which may occur independent of leptin signalling.

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Impaired postprandial apolipoprotein-B48 metabolism in the obese, insulin-resistant JCR:LA-cp rat: Increased atherogenicity for the metabolic syndrome

Cited by 83 publications

References 43 publications

Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance

Key intestinal genes involved in lipoprotein metabolism are downregulated in dyslipidemic men with insulin resistance

Cardiometabolic and reproductive benefits of early dietary energy restriction and voluntary exercise in an obese PCOS-prone rodent model

Effects of feeding fish oil on mesenteric lymph node cytokine responses in obese leptin receptor-deficient JCR:LA-cp rats

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