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

2003 ◽  
Vol 104 (4) ◽  
pp. 383-388 ◽  
Author(s):  
Dick C. CHAN ◽  
Gerald F. WATTS ◽  
P. Hugh R. BARRETT ◽  
Frans H. O'NEILL ◽  
Trevor G. REDGRAVE ◽  
...  

The dysmetabolic syndrome of insulin resistance and visceral obesity is characterized by elevated plasma concentration of triacylglycerol-rich lipoprotein (TRL) remnants that may be related to increased cardiovascular risk. Perturbed hepato-intestinal cholesterol metabolism may play a contributory role in this abnormality. We therefore investigated the association between plasma markers of cholesterol absorption and synthesis with TRL remnant metabolism in 35 men with the metabolic syndrome (MS). Plasma campesterol:cholesterol and lathosterol:cholesterol ratios were measured as estimates of cholesterol absorption and synthesis respectively. Remnant metabolism was assessed by measuring remnant-like particle-cholesterol (RLP-C), apolipoprotein (apo)B-48 and the fractional catabolic rate (FCR) of a labelled remnant-like emulsion. Compared with controls, subjects with the MS had significantly lower plasma campesterol:cholesterol ratio, but higher lathosterol:cholesterol ratio (P<0.05). Plasma RLP-C and apoB-48 concentrations were also higher (P<0.01) and the remnant-like emulsion FCR was lower (P<0.05). The plasma campesterol:cholesterol ratio was inversely correlated (P<0.05) with plasma triacylglycerols (r =-0.346), RLP-C (r =-0.443), apoB-48 (r =-0.427) and plasma lathosterol:cholesterol ratio (r =-0.366); the campesterol:cholesterol ratio was also positively correlated with the remnant-like emulsion FCR (r = 0.398, P<0.05). In multiple regression analysis, the significant correlations between plasma campesterol:cholesterol ratio and plasma triacylglycerols, RLP-C, apoB-48 and FCR of the remnant-like emulsion were independent of age, dietary energy and plasma lathosterol. Our findings suggest that in subjects with the MS alterations in cholesterol absorption and synthesis may be closely linked with the kinetic defects in TRL metabolism.

2007 ◽  
pp. 749-755
Author(s):  
A Šmahelová ◽  
R Hyšpler ◽  
T Haas

Using non-cholesterol sterols investigation several authors postulated a hypothesis that in the metabolic syndrome cholesterol endogenous synthesis is increased and its absorption decreased. Our study is the first attempt to evaluate the direct relation of cholesterol metabolism to the principal pathogenetic phenomenon of the metabolic syndrome--namely to insulin resistance. We have measured insulin sensitivity by two methods--Quicki (Quantitative Sensitivity Check Index) and intravenous insulin tolerance test (Kitt) and 3 indirect markers--fasting insulin level, fasting C-peptide level and SHBG (sex hormone binding globulin). The investigation was performed in three groups of subjects with a different prevalence of insulin resistance: 72 non-diabetics with ischemic heart disease, 117 young blood donors and 63 type 2 diabetics on diet therapy only. Analyzing altogether 60 relationships--between four sterols (lathosterol, squalene, sitosterol and campesterol) and five markers of insulin resistance in three groups of subjects--we have found only six significant relations between cholesterol synthesis and absorption and insulin resistance in all groups of patients. Our results indicate that there exists a significant relationship between insulin sensitivity and indices of either increased cholesterol synthesis or decreased cholesterol absorption. Insulin resistance explains only a part of both abnormalities mentioned above.


2007 ◽  
Vol 30 (4) ◽  
pp. 95
Author(s):  
Valerie Taylor ◽  
Glenda M. MacQueen

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


2019 ◽  
Vol 2019 ◽  
pp. 1-8 ◽  
Author(s):  
Daria Kupczyk ◽  
Renata Studzińska ◽  
Rafał Bilski ◽  
Alina Woźniak

The metabolic syndrome is defined by impaired carbohydrate metabolism and lipid disorders and often accompanied by hypertension, all of which will lead to obesity and insulin resistance. Glucocorticoids play a regulatory role in the metabolism of proteins, lipids, and carbohydrates. There is growing evidence for a role of glucocorticoids in the development of the metabolic syndrome. The most important factor that regulates the access of endogenous glucocorticoids to receptors after release of glucocorticoids and their diffusion into the cytoplasm of target cells is the steroid metabolism involving a microsomal enzyme, 11β-hydroxysteroid dehydrogenase (11β-HSD). The changes in intracellular glucocorticoid metabolism in the pathogenesis of obesity indicate the participation of modulation by 11β-HSD1, which may represent a new therapeutic target for the treatment of diseases such as type 2 diabetes, visceral obesity, or atherosclerosis. The aim of our study was to determine the fast and effective method to assess inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase. The material for this study was human liver and kidney microsomes. In this study we used ELISA technique using 96-well microplates coated with antibodies which were specific for analyzed enzymes. The method can quickly and efficiently measure the inhibition of both 11β-HSD1 and 11β-HSD2. This method can be used to search for and determine inhibitors of this enzyme. Cortisone and cortisol were used as the substrates for corresponding enzyme assays. Furthermore, 3-N-allyl-2-thiouracil derivatives were used by us for comparison purposes in developing the method, although, due to their structure, those derivatives have not previously been considered as potential inhibitors of 11β-HSD1. 3-N-Allyl-2-thiouracil derivatives are a group worth considering, because by modifying their structure (e.g., by introducing other substituents into the pyrimidine ring) it will be possible to obtain an increase in the activity of compounds in this regard. In conclusion, this study shows an efficient and fast method of determining inhibition activity of compounds in relation with 11β-hydroxysteroid dehydrogenase.


2016 ◽  
Vol 11 (1) ◽  
pp. 33-43 ◽  
Author(s):  
Dragana Lovre ◽  
Sarah H. Lindsey ◽  
Franck Mauvais-Jarvis

The world population is aging, and women will spend an increasing share of their lives in a postmenopausal state that predisposes to metabolic dysfunction. Thus, the prevalence of metabolic syndrome (MetS) in women is likely to increase dramatically. This article summarizes the effects of menopause in predisposing to components of MetS including visceral obesity, dyslipidemia, type 2 diabetes (T2D) and hypertension (HTN). We also summarize the effects of menopausal hormone therapy (MHT) in reversing these metabolic alterations and discuss therapeutic advances of novel menopausal treatment on metabolic function.


2011 ◽  
Vol 107 (5) ◽  
pp. 705-711 ◽  
Author(s):  
Caroline Richard ◽  
Patrick Couture ◽  
Sophie Desroches ◽  
Suzanne Benjannet ◽  
Nabil G. Seidah ◽  
...  

The mechanisms implicated in the LDL-cholesterol (LDL-C)-lowering effects of the Mediterranean-type diet (MedDiet) are unknown. The present study assessed the impact of the MedDiet consumed under controlled feeding conditions, with and without weight loss, on surrogate markers of cholesterol absorption, synthesis and clearance using plasma phytosterols, lathosterol and proprotein convertase subtilisin/kexin-9 (PCSK9) concentrations, respectively, in men with the metabolic syndrome. The subjects' diet (n19, 24–62 years) was first standardised to a baseline North American control diet (5 weeks) followed by a MedDiet (5 weeks), both under weight-maintaining isoenergetic feeding conditions. The participants then underwent a 20-week free-living energy restriction period (10 (sd3) % reduction in body weight,P < 0·01), followed by the consumption of the MedDiet (5 weeks) under controlled isoenergetic feeding conditions. The LDL-C-lowering effect of the MedDiet in the absence of weight loss ( − 9·9 %) was accompanied by significant reductions in plasma PCSK9 concentrations ( − 11·7 %,P < 0·01) and in the phytosterol:cholesterol ratio ( − 9·7 %,P < 0·01) compared with the control diet. The addition of weight loss to the MedDiet had no further impact on plasma LDL-C concentrations and on these surrogate markers of LDL clearance and cholesterol absorption. The present results suggest that the MedDiet reduces plasma LDL-C concentrations primarily by increasing LDL clearance and reducing cholesterol absorption, with no synergistic effect of body weight loss in this process.


Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 3177-3177
Author(s):  
Francesco Dentali ◽  
Cihan Ay ◽  
Moon Jang ◽  
Matteo di Minno ◽  
Ingrid Pabinger ◽  
...  

Abstract Abstract 3177 Background: The metabolic syndrome (MS) is a cluster of interrelated risk factors that identify patients at increased risk of cardiovascular events. Recent studies also suggested an association between MS and venous thromboembolism (VTE). However, the role of the individual features of MS and whether MS and its features are more important than obesity alone to predict VTE remain to be established. Methods: We performed an individual patient level meta-analysis of case-control studies comparing the prevalence of MS in patients with unprovoked VTE and in controls. MEDLINE, EMBASE databases, and abstract books were searched up to January 2010. Odds ratios (OR) and 95% confidence intervals of pooled results were calculated. The influence of individual variables (age, sex, BMI and MS) on the likelihood of VTE was compared using logistic regression analysis. Multivariate analysis was subsequently performed including the individual components of MS in the place of MS. The impact of increasing number of individual components of MS on the risk of VTE was investigated. Results: Four studies were identified and analyzed, for a total of 1332 patients (479 cases and 833 controls). Mean age was 53.3 and 52.7, respectively (p=n.s.), 49.5% cases and 42.4% controls were males (p=0.0003), 38.8% and 30.0% were obese (p=0.0001). MS was significantly associated with VTE (OR 1.97, 1.57–2.47), and the association linearly increased with the number of MS features (p for trend <0.001). At multivariate analysis, MS but not obesity remained associated with VTE (OR 1.92, 1.50–2.46 and 1.14, 0.88–1.47, respectively). All individual features of MS, but HDL cholesterol, were independently associated with VTE. Conclusions: The results of this meta-analysis confirm the association between MS and VTE and suggest that MS (and visceral obesity defined by increased waist circumference) could be a more important predictor of VTE than obesity defined by BMI. Disclosures: No relevant conflicts of interest to declare.


2007 ◽  
Vol 383 (1-2) ◽  
pp. 126-132 ◽  
Author(s):  
Maarit Hallikainen ◽  
Marjukka Kolehmainen ◽  
Ursula Schwab ◽  
David E. Laaksonen ◽  
Leo Niskanen ◽  
...  

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