Lipoprotein transport in the metabolic syndrome: methodological aspects of stable isotope kinetic studies

2004 ◽  
Vol 107 (3) ◽  
pp. 221-232 ◽  
Author(s):  
Dick C. CHAN ◽  
P. Hugh R. BARRETT ◽  
Gerald F. WATTS
Keyword(s):  
Metabolic Syndrome ◽  
Stable Isotope ◽  
Plasma Concentrations ◽  
Lipoprotein Metabolism ◽  
Visceral Obesity ◽  
Kinetic Studies ◽  
Kinetic Properties ◽  
The Metabolic Syndrome ◽  
Methodological Aspects

The metabolic syndrome encapsulates visceral obesity, insulin resistance, diabetes, hypertension and dyslipidaemia. Dyslipidaemia is a cardinal feature of the metabolic syndrome that accelerates the risk of cardiovascular disease. It is usually characterized by high plasma concentrations of triacylglycerol (triglyceride)-rich and apoB (apolipoprotein B)-containing lipoproteins, with depressed concentrations of HDL (high-density lipoprotein). However, lipoprotein metabolism is complex and abnormal plasma concentrations can result from alterations in the rates of production and/or catabolism of these lipoprotein particles. Our in vivo understanding of kinetic defects in lipoprotein metabolism in the metabolic syndrome has been achieved chiefly by ongoing developments in the use of stable isotope tracers and mathematical modelling. This review deals with the methodological aspects of stable isotope kinetic studies. The design of in vivo turnover studies requires considerations related to stable isotope tracer administration, duration of sampling protocol and interpretation of tracer data, all of which are critically dependent on the kinetic properties of the lipoproteins under investigation. Such models provide novel insight that further understanding of metabolic disorders and effects of treatments. Future investigations of the pathophysiology and therapy of the dyslipoproteinaemia of the metabolic syndrome will require the development of novel kinetic methodologies. Specifically, new stable isotope techniques are required for investigating in vivo the turnover of the HDL subpopulation of particles, as well as the cellular efflux of cholesterol into the extracellular space and its subsequent transport in plasma and metabolic fate in the liver.

Adiponectin: a key adipocytokine in metabolic syndrome

2006 ◽  
Vol 110 (3) ◽  
pp. 267-278 ◽  
Author(s):  
Yoshihisa Okamoto ◽  
Shinji Kihara ◽  
Tohru Funahashi ◽  
Yuji Matsuzawa ◽  
Peter Libby
Keyword(s):  
Metabolic Syndrome ◽  
Plasma Concentrations ◽  
Visceral Obesity ◽  
Clinical Intervention ◽  
Type Ii Diabetes Mellitus ◽  
Experimental Investigations ◽  
Novel Therapy ◽  
Mortality And Morbidity ◽  
The Metabolic Syndrome

The metabolic syndrome, a cluster of metabolic disorders often associated with visceral obesity, increases cardiovascular mortality and morbidity. As the body's largest endocrine organ, adipose tissue not only stores excess body energy, but also secretes a variety of bioactive adipocytokines. Obese patients, particularly those with visceral fat accumulation, have reduced plasma levels of adiponectin, the most abundant and adipose-specific adipocytokine. Although the association of adiponectin with several diseases remains controversial, many clinical studies have demonstrated that low plasma concentrations of adiponectin (hypoadiponectinaemia) associate closely with obesity-related diseases, including atherosclerotic cardiovascular diseases, Type II diabetes mellitus, hypertension and dyslipidaemia. Accumulating experimental evidence indicates that adiponectin possesses anti-atherogenic, anti-inflammatory and anti-diabetic properties and may also participate importantly in the mechanism of metabolic syndrome and other diseases. Despite these associations, further clinical and experimental investigations will be needed to illuminate the in vivo pathophysiological significance of this protein. Although evaluation of adiponectin as a novel therapy will ultimately require clinical intervention studies, this mediator may represent a novel target for the prevention and treatment of visceral obesity metabolic syndrome.

Lipoprotein transport in the metabolic syndrome: pathophysiological and interventional studies employing stable isotopy and modelling methods

2004 ◽  
Vol 107 (3) ◽  
pp. 233-249 ◽  
Author(s):  
Dick C. CHAN ◽  
P. Hugh R. BARRETT ◽  
Gerald F. WATTS
Keyword(s):  
Metabolic Syndrome ◽  
Stable Isotope ◽  
Low Density Lipoprotein ◽  
Lipoprotein Metabolism ◽  
Density Lipoprotein ◽  
Mechanisms Of Action ◽  
Biological Data ◽  
Low Density ◽  
The Metabolic Syndrome ◽  
Modelling Methods

The accompanying review in this issue of Clinical Science [Chan, Barrett and Watts (2004) Clin. Sci. 107, 221–232] presented an overview of lipoprotein physiology and the methodologies for stable isotope kinetic studies. The present review focuses on our understanding of the dysregulation and therapeutic regulation of lipoprotein transport in the metabolic syndrome based on the application of stable isotope and modelling methods. Dysregulation of lipoprotein metabolism in metabolic syndrome may be due to a combination of overproduction of VLDL [very-LDL (low-density lipoprotein)]-apo (apolipoprotein) B-100, decreased catabolism of apoB-containing particles and increased catabolism of HDL (high-density lipoprotein)-apoA-I particles. These abnormalities may be consequent on a global metabolic effect of insulin resistance, partly mediated by depressed plasma adiponectin levels, that collectively increases the flux of fatty acids from adipose tissue to the liver, the accumulation of fat in the liver and skeletal muscle, the hepatic secretion of VLDL-triacylglycerols and the remodelling of both LDL (low-density lipoprotein) and HDL particles in the circulation. These lipoprotein defects are also related to perturbations in both lipolytic enzymes and lipid transfer proteins. Our knowledge of the pathophysiology of lipoprotein metabolism in the metabolic syndrome is well complemented by extensive cell biological data. Nutritional modifications may favourably alter lipoprotein transport in the metabolic syndrome by collectively decreasing the hepatic secretion of VLDL-apoB and the catabolism of HDL-apoA-I, as well as by potentially increasing the clearance of LDL-apoB. Several pharmacological treatments, such as statins, fibrates or fish oils, can also correct the dyslipidaemia by diverse kinetic mechanisms of action, including decreased secretion and increased catabolism of apoB, as well as increased secretion and decreased catabolism of apoA-I. The complementary mechanisms of action of lifestyle and drug therapies support the use of combination regimens in treating dyslipoproteinaemia in subjects with the metabolic syndrome.

Prevalence of metabolic syndrome in never treated mood disordered patientss

2007 ◽  
Vol 30 (4) ◽  
pp. 95
Author(s):  
Valerie Taylor ◽  
Glenda M. MacQueen
Keyword(s):  
Metabolic Syndrome ◽  
Mood Disorders ◽  
Population Attributable Risk ◽  
Disease Process ◽  
Visceral Obesity ◽  
Premature Mortality ◽  
Overweight And Obesity ◽  
The Metabolic Syndrome ◽  
Increased Risk ◽  
Bipolar Patients

Bipolar disorder and major depression are life-shortening illnesses. Unnatural causes such as suicide and accidents account for only a portion of this premature mortality1 Research is beginning to identify that mood disordered patients have a higher incidence of metabolic syndrome, an illness characterized by dyslipidemia, impaired glucose tolerance, hypertension and obesity.2 Metabolic syndrome is associated with an increased risk for a variety of physical illnesses. Hypothesis: Never treated patients with mood disorders have preexisting elevations in the prevalence of the component variables of metabolic syndrome. Central obesity will be especially elevated, predicting increased premature mortality. Methods: We assessed never treated patients with mood disorders for metabolic syndrome and its component variables. Patients were assessed at baseline and followed up at 6-month intervals. All psychiatric pharmacotherapy was documented. Body mass index (BMI) was also obtained and the percentage of deaths attributable to overweight and obesity was calculated using the population attributable risk (PAR). [PAR= ∑[P (RR-1)/RR] Results: Prior to the initiation of treatment, patients did not differ from population norms with respect to metabolic syndrome or BMI. At 2-year follow-up, BMI had increased for unipolar patients 2.02 points and 1.92 points for bipolar patients. (p < .001) This increase in BMI predicted an increase in mortality of 19.4%. Conclusion: An increase in visceral obesity is often the first component of metabolic syndrome to appear and may indicate the initiation of this disease process prematurely in this group. The increase in BMI places patients with mood disorders at risk for premature mortality and indicates a need for early intervention. References 1.Osby U, Brandt L, Correia N, Ekbom A & Sparen P. Excess mortability in bipolar and Unipolar disorder rin Sweden. Archives of General Psychiatry, 2001;58: 844-850 2.Toalson P, Saeeduddin A, Hardy T & Kabinoff G. The metabolic syndrome in patients with severe mental illness. Journal of Clinical Psychiatry, 2004; 6(4): 152-158

Abstract W P386: Matrix Metalloproteinase Levels May Mediate Ischemic Stroke Incidence and Recovery in Stroke Patients with Metabolic Syndrome

Stroke ◽  
2015 ◽  
Vol 46 (suppl_1) ◽  
Author(s):  
Ashley B Petrone ◽  
Taura L Barr ◽  
Kelly Devlin ◽  
Sara B Fournier ◽  
Evan D Devallance ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Stroke Risk ◽  
Plasma Concentrations ◽  
Stroke Recovery ◽  
Ultrasound Images ◽  
Stroke Patients ◽  
Stroke Incidence ◽  
The Metabolic Syndrome ◽  
Diabetes Status ◽  
Increased Risk

Intro: The metabolic syndrome (MetS) is highly prevalent in the US characterized by a combination of risk factors that can lead to cardiovascular disease (CVD). While the association between CVD, inflammation, and stroke risk has been characterized, the immune mechanisms underlying increased risk of stroke in MetS is unclear. While stroke risk is higher among MetS, MetS individuals tend to have better stroke recovery than controls. The immune response may mediate these paradoxical observations in stroke. In particular, matrix metalloproteinases (MMP) enzymes play a role in stroke incidence and recovery. Similar to MetS, MMPs have a dual role in stroke, as they are harmful immediately after stroke, but play a vital role in brain repair and recovery following stroke. We hypothesize that elevated levels of MMPs in MetS may account for the paradoxical increased stroke risk, yet better recovery seen in stroke patients with MetS. Methods: MMP protein concentrations were obtained from fasting venous samples and quantified using a Multi-Analyte Profiling Kit (Millipore) on the Luminex®. Each subject was assigned a metabolic risk score (MRS) based on sex, age, SBP, treatment for hypertension, smoking and diabetes status, HDL, and total cholesterol. B-mode ultrasound images of the right common carotid artery were obtained to measure intima-medial thickness (cIMT). Spearman correlations were used to measure the relationship between MRS, cIMT, and MMP levels. Results: In n=68 subjects (60% female) with a mean age of 48+14 yrs, MRS of 25+12, and cIMT of 0.57+0.12 mm. MRS was significantly correlated with cIMT (r=0.39, p< .001). Further, cIMT was positively correlated with MMP1 (r=0.025, p=0.04), MMP7 (r=0.5, p=0.01), and MMP9 (r=0.31, p=0.01). Conclusion: Plasma concentrations of MMP1, 7, and 9 were significantly correlated with cIMT, indicating that increased severity of MetS is associated with increased inflammation. Elevated MMP protein levels may account for the increased stroke risk, yet better recovery seen in stroke patients with MetS.

scholarly journals Enhanced phosphorylation of Na+–Cl− co-transporter in experimental metabolic syndrome: role of insulin

2012 ◽  
Vol 123 (11) ◽  
pp. 635-647 ◽  
Author(s):  
Radko Komers ◽  
Shaunessy Rogers ◽  
Terry T. Oyama ◽  
Bei Xu ◽  
Chao-Ling Yang ◽  
...  
Keyword(s):  
Metabolic Syndrome ◽  
Time Course ◽  
Kinase Inhibitor ◽  
Endogenous Expression ◽  
The Metabolic Syndrome ◽  
Mammalian Cell Lines ◽  
Phosphoinositide 3 Kinase

In the present study, we investigated the activity of the thiazide-sensitive NCC (Na+–Cl− co-transporter) in experimental metabolic syndrome and the role of insulin in NCC activation. Renal responses to the NCC inhibitor HCTZ (hydrochlorothiazide), as a measure of NCC activity in vivo, were studied in 12-week-old ZO (Zucker obese) rats, a model of the metabolic syndrome, and in ZL (Zucker lean) control animals, together with renal NCC expression and molecular markers of NCC activity, such as localization and phosphorylation. Effects of insulin were studied further in mammalian cell lines with inducible and endogenous expression of this molecule. ZO rats displayed marked hyperinsulinaemia, but no differences in plasma aldosterone, compared with ZL rats. In ZO rats, natriuretic and diuretic responses to NCC inhibition with HCTZ were enhanced compared with ZL rats, and were associated with a decrease in BP (blood pressure). ZO rats displayed enhanced Thr53 NCC phosphorylation and predominant membrane localization of both total and phosphorylated NCC, together with a different profile in expression of SPAK (Ste20-related proline/alanine-rich kinase) isoforms, and lower expression of WNK4. In vitro, insulin induced NCC phosphorylation, which was blocked by a PI3K (phosphoinositide 3-kinase) inhibitor. Insulin-induced reduction in WNK4 expression was also observed, but delayed compared with the time course of NCC phosphorylation. In summary, we report increased NCC activity in hyperinsulinaemic rodents in conjunction with the SPAK expression profile consistent with NCC activation and reduced WNK4, as well as an ability of insulin to induce NCC stimulatory phosphorylation in vitro. Together, these findings indicate that hyperinsulinaemia is an important driving force of NCC activity in the metabolic syndrome with possible consequences for BP regulation.

scholarly journals Lipid Peroxidation as a Link Between Unhealthy Diets and the Metabolic Syndrome

2021 ◽  
Author(s):  
Arnold N. Onyango
Keyword(s):  
Oxidative Stress ◽  
Metabolic Syndrome ◽  
Lipid Peroxidation ◽  
Lipid Oxidation ◽  
Saturated Fatty Acids ◽  
Radical Scavenging ◽  
The Metabolic Syndrome ◽  
Mechanisms Of Formation ◽  
Obesity Hypertension

Unhealthy diets, such as those high in saturated fat and sugar accelerate the development of non-communicable diseases. The metabolic syndrome is a conglomeration of disorders such as abdominal obesity, hypertension, impaired glucose regulation and dyslipidemia, which increases the risk for diabetes and cardiovascular disease. The prevalence of the metabolic syndrome is increasing globally, and dietary interventions may help to reverse this trend. A good understanding of its pathophysiological mechanisms is needed for the proper design of such interventions. This chapter discusses how lipid peroxidation is associated with the development of this syndrome, mainly through the formation of bioactive aldehydes, such as 4-hydroxy-2-nonenal, malondialdehyde, acrolein and glyoxal, which modify biomolecules to induce cellular dysfunction, including the enhancement of oxidative stress and inflammatory signaling. It gives a current understanding of the mechanisms of formation of these aldehydes and how dietary components such as saturated fatty acids promote oxidative stress, leading to lipid oxidation. It also outlines mechanisms, apart from free radical scavenging and singlet oxygen quenching, by which various dietary constituents prevent oxidative stress and lipid oxidation in vivo.

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