The World Health Organization (WHO), National Cholesterol Education Program Adults Treatment Panel III (NCEP ATP III) and International Diabetes Federation (IDF) have proposed different criteria to diagnose metabolic syndrome (MetS). However, there is no single definition to accurately diagnose MetS. The objective of this study is to estimate the prevalence of MetS using WHO, NCEP ATP III and IDF in the Malaysian community, and to determine the concordance between these definitions for MetS. 109 men and women aged > 30 years participated in the study, and the prevalence of MetS was determined according to the three definitions. Weight, height, body mass index (BMI), waist-hip circumference, blood pressure, blood lipid profile and plasma fasting glucose were measured. In order to determine the concordance between IDF and the other two definitions, the kappa index (κ-test) was used. The prevalence of MetS (95% confidence interval) was 22.9% (22.8-23.1) by IDF definition, 16.5% (16.3-16.9) by NCEP ATP III definition and 6.4% (6.2-6.6) by modified WHO definition. The sensitivity and specificity of IDF against NCEP ATP III were 88.9% and 90.1% respectively, IDF against WHO definition were 85.7% and 81.4%. The κ statistics for the agreement of the IDF definition was 68.3 ± 0.1 with the NCEP ATP III, and 30.5 ± 0.1 with the modified WHO definition. The prevalence of the MetS among respondents using the IDF definition was highest, followed by NCEP ATP III, and finally modified WHO definition. There was a good concordance between the IDF and NCEP ATP III definitions, and a low concordance between IDF and modified WHO definitions.
Withdrawal from long-term ethanol consumption results in overexcitation of glutamatergic neurotransmission in the amygdala, which induces an anxiety-like syndrome. Most alcoholics that suffer from such symptoms frequently depend on habitual drinking as self-medication to alleviate their symptoms. Metabotropic glutamate receptor subtype 5 (mGlu5) and protein kinase C (PKC) epsilon have been reported to mediate acute and chronic effects of ethanol. This study explores the changes in mGlu5 and PKC epsilon in the amygdala following acute administration of ethanol during ethanol withdrawal (EW) induced anxiety. Male Wistar rats were fed a modified liquid diet containing low-fat cow milk, sucrose, and maltodextrin, with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into EW, the rats were intraperitoneally injected with normal saline and ethanol (2.5 g/kg, 20% v/v), and exposed to open-field and elevated plus maze tests. Then, amygdala tissue was dissected from the rat brain for Western blot and gene expression studies. EW-induced anxiety was accompanied by a significant increase in mGlu5, total PKC epsilon, and phosphorylated PKC epsilon protein levels, and also of mRNA of mGlu5 (GRM5) in the amygdala. Acute administration of ethanol significantly attenuated EW-induced anxiety as well as an EW-induced increase in GRM5. The acute challenge of ethanol to EW rats had little effect on the phosphorylated and total protein levels of PKC epsilon in the amygdala. Our results demonstrate that amygdala PKC epsilon may not be directly involved in the development of anxiety following EW.
This study was conducted to determine the mRNA and protein expression levels of peroxisome proliferator-activated receptors (PPARs) in visceral adipose tissue, as well as serum adipokine levels, in Sprague Dawley rats. The rats were fed either a normal (control rats) or excessive (experimental rats) intake of food for 8 or 16 weeks, then sacrificed, at which time visceral and subcutaneous adipose tissues, as well as blood samples, were collected. The mRNA and protein expression levels of PPARs in the visceral adipose tissues were determined using reverse transcription-polymerase chain reaction and Western blotting, respectively. In addition, the levels of adipokines in the serum samples were determined using commercial ELISA kits. The results revealed that at 8 weeks, the mass of subcutaneous adipose tissue was higher than that of the visceral adipose tissue in the experimental rats, but the reverse occurred at 16 weeks. Furthermore, at 16 weeks the experimental rats exhibited an upregulation of PPARγ mRNA and protein expression levels in the visceral adipose tissues, and significant increases in the serum levels of CCL2 and interleukin (IL)-6 were observed, compared with those measured at 8 weeks. In conclusion, this study demonstrated that the PPARγ expression level was likely correlated with serum levels of CCL2 and IL-6, molecules that may facilitate visceral adipose tissue accumulation. In addition, the levels of the two adipokines in the serum may be useful as surrogate biomarkers for the expression levels of PPARγ in accumulated visceral adipose tissues.
Abstinence from chronic ethanol consumption leads to the manifestation of a variety of symptoms attributed to central nervous system hyperexcitability, such as increased irritability, anxiety, and restlessness. Recent studies have demonstrated the importance of metabotropic glutamate receptor 5 (mGluR5) in addictive behaviours. This study investigates the effects of the mGluR5 antagonist 2-methyl-6-(phenylethynyl)-pyridine (MPEP) on ethanol withdrawal induced anxiety using two behavioural paradigms. Male Wistar rats were fed a Modified Liquid Diet (MLD) containing low fat cow milk, sucrose, and maltodextrin with a gradual introduction of 2.4%, 4.8% and 7.2% ethanol for 20 days. Six hours into ethanol withdrawal, the rats were intraperitoneally injected with normal saline and MPEP (2.5, 5.0, 10, 20, 30 mg/kg) and were assessed for ethanol withdrawal induced anxiety-like syndrome using an automated elevated plus maze and an open field. MPEP at 10 mg/kg significantly attenuated ethanol withdrawal induced anxiety without any compromising effects on locomotor activities. Despite reversing several indices of ethanol withdrawal induced anxiety in both the elevated plus maze and the open field, low doses of MPEP (2.5, 5 mg/kg) significantly compromised the locomotor activities of ethanol withdrawn rats. High doses of MPEP (20 and 30 mg/kg) significantly attenuated withdrawal anxiety when tested in the elevated plus maze but not in the open field. Administration of MPEP (2.5, 5, 10, 20, 30 mg/kg) has no significant compromising effect on the locomotor activities of ethanol naïve rats. Despite significantly reducing withdrawal anxiety in both behavioural paradigms at 10 mg/kg, the compromising effects of low and high doses of MPEP must be further explored along with the therapeutic efficiency of this drug for relieving withdrawal induced anxiety.
INTRODUCTION: This study aims to assess microvascular endothelial function in obese compared to age matched lean controls. Serum lipid profile, fasting glucose, high sensitivity C-reactive protein (hs-CRP) and adiponectin levels were also determined.
METHODS: This cross-sectional study involved 36 healthy lean and 36 obese subjects. Microvascular endothelial function was assessed using Laser Doppler fluximetry and iontophoresis with acetylcholine and sodium nitroprusside.
RESULTS: Mean age of subjects was 26.54 ± 0.60 years. Obese subjects had higher systolic (118.8 ± 1.5 vs 105.7 ± 2.0 mmHg, p < 0.001) and diastolic blood pressure (71.61 ± 1.35 vs 64.53 ± 1.40 mmHg, p = 0.001), higher triglyceride (1.35 ± 0.13 vs 0.79 ± 0.05 mmol/l, p < 0.001), lower high density lipoprotein cholesterol (HDL-C) (1.43 ± 0.04 vs 1.62 ± 0.05 mmol/l, p = 0.003), higher hs-CRP (11.58 ± 1.88 vs 1.88 ± 0.35 mg/l, p < 0.001), and lower adiponectin levels (8.80 ± 0.43 vs 25.93 ± 0.40 μg/ml, p < 0.001) compared to lean subjects. Endothelial dependent vasodilatation was lower in obese compared to lean subjects (40.53 ± 6.59 vs 71.03 ± 7.13 AU, p = 0.001).
CONCLUSION: Microvascular endothelial function is reduced in obese compared to age matched controls. This is associated with higher BP, triglyceride and lower HDL-C and adiponectin levels in obese group.
Study site: not mentioned
INTRODUCTION: Obesity is associated with impaired microvascular endothelial function. We aimed to determine the effects of orlistat and sibutramine treatment on microvascular endothelial function, anthropometric and lipid profile, blood pressure (BP), and heart rate (HR).
METHODS: 76 subjects were recruited and randomized to receive orlistat 120 mg three times daily or sibutramine 10 mg daily for 9 months. Baseline weight, BMI, BP, HR and lipid profile were taken. Microvascular endothelial function was assessed using laser Doppler fluximetry and iontophoresis process. Maximum change (max), percent change (% change) and peak flux (peak) in perfusion to acetylcholine (ACh) and sodium nitroprusside (SNP) iontophoresis were used to quantify endothelium dependent and independent vasodilatations.
RESULTS: 24 subjects in both groups completed the trial. After treatment, weight and BMI were decreased for both groups. AChmax, ACh % change and ACh peak were increased in orlistat-treated group but no difference was observed for sibutramine-treated group. BP and total cholesterol (TC) were reduced for orlistat-treated group. HR was reduced for orlistat-treated group but was increased in sibutramine-treated group.
CONCLUSION: 9 months treatment with orlistat significantly improved microvascular endothelial function. This was associated with reductions in weight, BMI, BP, HR, TC and low density lipoprotein cholesterol. No effect was seen in microvascular endothelial function with sibutramine.
KEYWORDS: Microvascular endothelial function; obesity; orlistat; sibutramine
In the past decade, many studies have highlighted the role of metabotropic glutamate receptor subtype 5 (mGlu5) modulators in attenuating alcohol-related biological effects such as alcohol consumption, alcohol-seeking and relapse-like behaviors. Taken together, these findings suggest that pharmacological agents acting at mGlu5 could be promising tools in curbing inebriation. mGlu5s are present abundantly in brain regions known to be involved in emotion regulation, motivation and drug administration. On a cellular level, they are primarily located at the postsynaptic part of the neuron where the receptor is functionally linked to various downstream proteins that are involved in cell signaling and gene transcription that mediate the alcohol-induced neuroplasticity. As well, the discovery of a functional link between mGlu5 and a specific isozyme, Protein Kinase C epsilon (PKCε) in mediating the attenuating effects of selective negative allosteric modulators of mGlu5 such as methyl- 6(phenylethynyl)pyridine (MPEP) and 3-((2-methyl-4-thiazolyl)ethynyl)pyridine (MTEP) has sparked interesting speculations. In this article, we shall review the following: the effects of acute and chronic alcohol intake on mGlu5 signaling; the effects of mGlu5 ligands on alcohol-related neurobehavioral changes that are currently being studied both at pre-clinical and clinical stages; and the mechanisms underlying the pharmacological effects of these drugs.