Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome

CHAN, Dick C.; Watts, Gerald F.; Barrett, P. Hugh R.; O’Neill, F. H.; Redgrave, Trevor G.; Thompson, Gilbert R.

doi:10.1042/cs1040383

Cited by 30 publications

(20 citation statements)

References 17 publications

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“…18 However, the changes in cholesterol levels are often more directly associated to the consequences of insulin resistance and hyperinsulinaemia 19 than, to small extent, changes in insulin sensitivity such as those observed here. In addition, most effects of insulin resistance on cholesterol levels are mediated by the handling of lipoproteins, such as chylomicra remnants 20,21 or modulation of lipoprotein lipase. 16,22 The lack of changes in circulating triacylglycerol may point towards a limited extent of change in lipoprotein lipase, but OE is known to induce marked decreases in adipose tissue and increases in muscle lipoprotein lipase 3 that facilitate the transfer of lipid energy from adipose tissue to peripheral tissues.…”

Section: Discussionmentioning

confidence: 99%

Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

et al. 2005

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OBJECTIVE: Oral treatment with oleoyl-estrone induces the loss of body fat and improvement of insulin resistance. Since cholesterol levels are deeply affected by oleoyl-estrone, we investigated here whether short-term treatment affected cholesterol turnover and overall metabolite changes. DESIGN: Wistar female rats received a single oral dose of 10 mmol/kg oleoyl-estrone in 0.2 ml of sunflower oil. Groups of animals were killed at timed intervals and blood samples were taken. In a second experiment series, rats had implanted carotid and jugular cannulas and were given a single gavage of oleoyl-estrone. These rats were used for the measurement of the cholesterol turnover rate. MEASUREMENTS: Body weight change and food intake: Glucose, total and HDL-cholesterol, triacylglycerols, 3-hydroxybutyrate, nonesterified fatty acids, insulin, HOMA score in the rats of the first series. Cholesterol: Cholesterol pool changes and cholesterol turnover rates in the rats of the second series. RESULTS: OE induced early effects, decreasing food intake, cholesterol and HDL-cholesterol levels, and increasing insulin sensitivity (HOMA score). OE also increased cholesteryl-ester turnover, and decreased circulating total cholesterol, especially esterified cholesterol pools. CONCLUSIONS: The role of early changes in insulin sensitivity induced by oral OE cannot explain per se the deep changes in cholesterol handling, essentially a consequence of accelerated lipoprotein turnover. However, the increase in cholesteryl-ester turnover observed with OE treatment may be, at least in part, a consequence of the decrease in insulin resistance. The compounded effect of increased insulin sensitivity and accelerated lipoprotein turnover may help explain the early and marked hypocholesterolaemic effects of OE.

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Section: Discussionmentioning

confidence: 99%

Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

et al. 2005

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“…Furthermore, patients with the MetS had a low campesterol/ cholesterol ratio, indicative of reduced cholesterol absorption. 86 This ratio was inversely correlated with plasma levels of TG, remnant cholesterol, and apo B48.…”

Section: Lifestyle Changesmentioning

confidence: 94%

Pathophysiology of dyslipidaemia in the metabolic syndrome

Kolovou

Anagnostopoulou

Cokkinos

2005

Postgraduate Medical Journal

188

119

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The insulin resistance/metabolic syndrome is characterised by the variable coexistence of hyperinsulinaemia, obesity, dyslipidaemia, and hypertension. The pathogenesis of the syndrome has multiple origins, but obesity and sedentary lifestyle coupled with diet and still largely unknown genetic factors clearly interact to produce the syndrome. Dyslipidaemia, the hallmark of the metabolic syndrome, includes increased flux of free fatty acids, raised triglycerides, apolipoprotein B, and small dense low density lipoprotein, and decreased high density lipoprotein cholesterol. The widely prevalent nature of the metabolic syndrome emphasises the importance of its diagnosis and treatment. This review analyses the clinical and dynamic features of this syndrome in the aspect of dyslipidaemia and its management.

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“…A major metabolic abnormality associated with insulin resistance is dyslipidemia characterized by the overproduction of hepatic VLDL-apoB-100, which contributes to the increased risk of cardiovascular disease in this population (6)(7)(8). The failure of insulin to suppress hepatic de novo lipogenesis, increased free fatty acid (FFA) flux, TG synthesis, and decreased fatty acid oxidation collectively lead to increased VLDL overproduction.…”

Section: Discussionmentioning

confidence: 99%

“…Because insulin and naringenin inhibit apoB-100 secretion through activation of the same signaling mechanisms, we postulated that naringenin has the ability to potentiate the effects of insulin in HepG2 cells and that naringenin sensitizes cells to insulin. Thus, examination of the molecular events in hepatocytes exposed to naringenin may provide insight into novel mechanisms for reduction of hepatic overproduction of apoB-100-containing lipoproteins, a characteristic of the dyslipidemia associated with insulin resistance (6)(7)(8).…”

mentioning

confidence: 99%

Inhibition of apoB secretion from HepG2 cells by insulin is amplified by naringenin, independent of the insulin receptor

Allister

Mulvihill

Barrett

et al. 2008

Journal of Lipid Research

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Hepatic overproduction of apolipoprotein B (apoB)-containing lipoproteins is characteristic of the dyslipidemia associated with insulin resistance. Recently, we demonstrated that the flavonoid naringenin, like insulin, decreased apoB secretion from HepG2 cells by activation of both the phosphoinositide-3-kinase (PI3-K) pathway and the mitogen-activated protein kinase/extracellular-regulated kinase (MAPK erk ) pathway. In the present study, we determined whether naringenin-induced signaling required the insulin receptor (IR) and sensitized the cell to the effects of insulin, and whether the kinetics of apoB assembly and secretion in cells exposed to naringenin were similar to those of insulin. Immunoblot analysis revealed that insulin stimulated maximal phosphorylation of IR and IR substrate-1 after 10 min, whereas naringenin did not affect either at any time point up to 60 min. The combination of naringenin and submaximal concentrations of insulin potentiated extracellularregulated kinase 1/2 activation and enhanced upregulation of the LDL receptor, downregulation of microsomal triglyceride transfer protein expression, and inhibition of apoB-100 secretion. Multicompartmental modeling of apoB pulse-chase studies revealed that attenuation of secreted radiolabeled apoB in naringenin-or insulin-treated cells was similar under lipoprotein-deficient or oleate-stimulated conditions. Naringenin and insulin both stimulated intracellular apoB degradation via a kinetically defined rapid pathway. Therefore, naringenin, like insulin, inhibits apoB secretion through activation of both PI3-K and MAPK erk signaling, resulting in similar kinetics of apoB secretion. However, the mechanism for naringenin-induced signaling is independent of the IR. Naringenin represents a possible strategy for reduction of hepatic apoB secretion, particularly in the setting of insulin

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Relationships between cholesterol homoeostasis and triacylglycerol-rich lipoprotein remnant metabolism in the metabolic syndrome

Cited by 30 publications

References 17 publications

Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

Short-term oral oleoyl-estrone treatment increases plasma cholesterol turnover in the rat

Pathophysiology of dyslipidaemia in the metabolic syndrome

Inhibition of apoB secretion from HepG2 cells by insulin is amplified by naringenin, independent of the insulin receptor

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