Key Components Of Metabolic Syndrome Research Articles

Modern view of the problem: the influence of obesity as a key component of metabolic syndrome on the development and progression of endometrial cancer

Unlike many other malignancies, the incidence and mortality of endometrial cancer continues to rise. This unfortunate trend is in no small part the result of the worldwide obesity epidemic, which is caused by reduced physical activity, poor diet and chronic stress. Currently, more than 50 % of endometrial cancer cases are associated with obesity, which is recognized as an independent risk factor for the development of this disease. Adipose tissue is not only the main place of storage of excess energy, but also a full-fledged endocrine organ that affects the metabolism, immune response and production of biologically active substances involved in cell growth and differentiation, angiogenesis, apoptosis and carcinogenesis. In this review, we assess the impact of obesity as a key component of metabolic syndrome on the development and progression of endometrial cancer. There are several mechanisms by which obesity enlarges the risk of endometrial cancer, including increased endogenous sex steroid hormones, hyperglycemia, insulin resistance, adipokine secretion, and chronic inflammation. The purpose of this review is to analyze publications, reflecting the already known aspects of the biological effect of obesity, as well as new data from recent years.

Insulin resistance and metabolic syndrome as a risk factor for Alzheimer's Disease: systematic literature review

Introduction: It is estimated that worldwide, 65.7 million people will live with the disease in 2030, with Alzheimer's disease being the most prevalent in the world, accounting for 60% of dementia cases. The hypothesis was then raised that through the neuroprotective effect of insulin and insulin resistance in the genesis of Metabolic Syndrome, the hypothetical relationship is made that metabolic syndrome is a risk factor for Alzheimer's disease. Objective: The literature that verifies the impact of vitamin D deficiency on the quality of life of individuals undergoing bariatric surgery was reviewed. Methods: The search strategy was carried out in the virtual databases PubMed, Scielo, LILACS, Scopus, Web of Science, Embase, and Biblioteca Virtual em Saúde, in addition to gray literature such as Google Scholar, OpenGrey, Ibict/BDTD (Brazilian digital library of theses and dissertations) and ProQuest using the Medical Subject Headings (MeSH) and Health Sciences Descriptors (DeCS) descriptors with the Boolean logical operators AND, OR and NOT. The studies considered eligible were those that presented metabolic syndrome as a risk factor for the development of Alzheimer's disease. Results: The online search found 216 studies in virtual bibliographic databases and 70 in gray literature. After removing duplicates, 282 articles remained and were read the title and abstract, with 25 articles chosen for full-text reading, leaving 13 that met the inclusion criteria. Most of the studies included corroborated the hypothesis that metabolic syndrome is a risk factor for Alzheimer's disease. Even the two studies that provide some results in which BMI showed a slower decline in cognitive function, stated that the phenotype studied was that of metabolically healthy obese individuals. Conclusion: The results of this study confirmed the idea that there is an interaction between metabolic health and brain health. First, chronic inflammation and oxidative stress associated with metabolic syndrome can cause damage to blood vessels, compromising cerebral blood flow and impairing the supply of essential nutrients to the brain. Additionally, insulin resistance, one of the key components of metabolic syndrome, can hurt brain function by interfering with the absorption of glucose, a vital fuel for the brain. Finally, how changes in blood lipid levels can contribute to the accumulation of beta-amyloid protein plaques in the brain, one of the markers of Alzheimer's disease.

Pathogenesis of Hypertension in Metabolic Syndrome: The Role of Fructose and Salt.

Metabolic syndrome is manifested by visceral obesity, hypertension, glucose intolerance, hyperinsulinism, and dyslipidemia. According to the CDC, metabolic syndrome in the US has increased drastically since the 1960s leading to chronic diseases and rising healthcare costs. Hypertension is a key component of metabolic syndrome and is associated with an increase in morbidity and mortality due to stroke, cardiovascular ailments, and kidney disease. The pathogenesis of hypertension in metabolic syndrome, however, remains poorly understood. Metabolic syndrome results primarily from increased caloric intake and decreased physical activity. Epidemiologic studies show that an enhanced consumption of sugars, in the form of fructose and sucrose, correlates with the amplified prevalence of metabolic syndrome. Diets with a high fat content, in conjunction with elevated fructose and salt intake, accelerate the development of metabolic syndrome. This review article discusses the latest literature in the pathogenesis of hypertension in metabolic syndrome, with a specific emphasis on the role of fructose and its stimulatory effect on salt absorption in the small intestine and kidney tubules.

Breviscapine alleviates NASH by inhibiting TGF-β-activated kinase 1-dependent signaling.

Background and AimsNAFLD is a key component of metabolic syndrome, ranging from nonalcoholic fatty liver to NASH, and is now becoming the leading cause of cirrhosis and HCC worldwide. However, due to the complex and unclear pathophysiological mechanism, there are no specific approved agents for treating NASH. Breviscapine, a natural flavonoid prescription drug isolated from the traditional Chinese herb Erigeron breviscapus, exhibits a wide range of pharmacological properties, including effects on metabolism. However, the anti‐NASH efficacy and mechanisms of breviscapine have not yet been characterized.Approach and ResultsWe evaluated the effects of breviscapine on the development of hepatic steatosis, inflammation, and fibrosis in vivo and in vitro under metabolic stress. Breviscapine treatment significantly reduced lipid accumulation, inflammatory cell infiltration, liver injury, and fibrosis in mice fed a high‐fat diet, a high‐fat/high‐cholesterol diet, or a methionine‐ and choline‐deficient diet. In addition, breviscapine attenuated lipid accumulation, inflammation, and lipotoxicity in hepatocytes undergoing metabolic stress. RNA‐sequencing and multiomics analyses further indicated that the key mechanism linking the anti‐NASH effects of breviscapine was inhibition of TGF‐β‐activated kinase 1 (TAK1) phosphorylation and the subsequent mitogen‐activated protein kinase signaling cascade. Treatment with the TAK1 inhibitor 5Z‐7‐oxozeaenol abrogated breviscapine‐mediated hepatoprotection under metabolic stress. Molecular docking illustrated that breviscapine directly bound to TAK1.ConclusionBreviscapine prevents metabolic stress–induced NASH progression through direct inhibition of TAK1 signaling. Breviscapine might be a therapeutic candidate for the treatment of NASH.

Higher hemoglobin levels are an independent risk factor for adverse metabolism and higher mortality in a 20-year follow-up

The aim of this study was to cross-sectionally and longitudinally examine whether higher hemoglobin (Hb) levels within the normal variation associate with key components of metabolic syndrome and total and cardiovascular mortality. The study included 967 Finnish subjects (age 40–59 years) followed for ≥ 20 years. The focus was on Hb levels, cardiovascular diseases (CVDs) and mortality rates. Higher Hb levels associated positively with key anthropometric and metabolic parameters at baseline. At the follow-up similar associations were seen in men. The highest Hb quartile showed higher leptin levels and lower adiponectin levels at baseline and follow-up (p < 0.05) and lower plasma ghrelin levels at baseline (p < 0.05). Higher baseline Hb levels associated independently with prevalence of type 2 diabetes at follow-up (p < 0.01). The highest Hb quartile associated with higher serum alanine aminotransferase levels (p < 0.001) and independently with increased risk for liver fat accumulation (OR 1.63 [1.03; 2.57]) at baseline. The highest Hb quartile showed increased risk for total (HR = 1.48 [1.01; 2.16]) and CVD-related mortality (HR = 2.08 [1.01; 4.29]). Higher Hb levels associated with an adverse metabolic profile, increased prevalence of key components of metabolic syndrome and higher risk for CVD-related and total mortality.

An integrating strategy for serum metabolomics and microarray analysis to expand the understanding of diet-induced obesity.

Obesity is a key component of metabolic syndrome and is precipitated by complex interactions between multiple environmental and genetic factors. The integration of multi-level bioinformation is needed to understand the altered endogenous molecule and metabolic mechanisms. In this study, an integrated analytical strategy was proposed by combining microarray data from a gene expression omnibus database and in vitro serum metabolomic data to unearth bioinformation associated with cafeteria diet induced obesity. In the diet induced obese rats, 23 genes and 9 metabolites showed significant changes, in which the increased levels of alanine, lactate and lactate dehydrogenase B (Ldhb) and the decreased levels of citrate and pyruvate indicated an enhanced glycolysis and a disordered Krebs cycle. Furthermore, the closeness centrality of Slc27a2, Apobr, alanine and histidine in the correlations network of pathways, genes and metabolites was 0.5036, 0.5111, 0.5702, and 0.5352, respectively. These close links between metabolites and genes would be highly useful to assess the degree of obesity and to understand the developmental mechanism of obesity. The pathway enrichment analysis of genes and metabolites proved that a disturbed glucose metabolism and biosynthesis of amino acids are typical metabolic features of cafeteria-induced obesity. The metabolomics combined with microarray data not only could identify the biomarkers, but also would be beneficial to the follow-up research of obesity treatment, especially providing a methodological basis for the study of other diseases.

Anti‐hyperlipidaemic effects of synthetic analogues of nordihydroguaiaretic acid in dyslipidaemic rats

Previous studies have shown that Creosote bush-derived nordihydroguaiaretic acid (NDGA) exerts beneficial actions on the key components of metabolic syndrome including dyslipidaemia, insulin resistance and hypertension in several relevant rodent models. Here, we synthesized and screened a total of 6 anti-hyperlipidaemic analogues of NDGA and tested their efficacy against hepatic lipid metabolism in a high-fructose diet (HFrD) fed dyslipidaemic rat model. HFrD fed Sprague-Dawley rats treated with NDGA or one of the six analogues were used. Serum samples were analysed for blood metabolites, whereas liver samples were quantified for changes in various mRNA levels by real-time RT-PCR. Oral gavage of HFrD-fed rats for 4days with NDGA analogues 1 and 2 (100mg·kg-1 ·day-1 ) suppressed the hepatic triglyceride content, whereas the NDGA analogues 2, 3 and 4, like NDGA, decreased the plasma triglyceride levels by 70-75%. qRT-PCR measurements demonstrated that among NDGA analogues 1, 2, 4 and 5, analogue 4 was the most effective at inhibiting the mRNA levels of some key enzymes and transcription factors involved in lipogenesis. All four analogues almost equally inhibited the key genes involved in triglyceride synthesis and fatty acid elongation. Unlike NDGA, none of the analogues affected the genes of hepatic fatty acid oxidation or transport. Our data suggest that NDGA analogues 1, 2, 4 and 5, particularly analogue 4, exert their anti-hyperlipidaemic actions by negatively targeting genes of key enzymes and transcription factors involved in lipogenesis, triglyceride synthesis and fatty acid elongation. These analogues have therapeutic potential.

SIRT3 deficiency-induced mitochondrial dysfunction and inflammasome formation in the brain

SIRT3, the primary mitochondrial deacetylase, plays a significant role in enhancing the function of mitochondrial proteins. Downregulation of SIRT3 is a key component of metabolic syndrome, a precondition for obesity, diabetes and cardiovascular diseases. In this study, we examined the effects of brain mitochondrial protein hyperacetylation in western diet-fed Sirt3−/− mice, a model for metabolic syndrome. Brain mitochondrial proteins were hyperacetylated, following western diet feeding and Sirt3 deletion. To identity these hyperacetylated proteins, we performed a comprehensive acetylome analysis by label-free tandem mass spectrometry. Gene ontology pathway analysis revealed Sirt3 deletion-mediated downregulation of enzymes in several metabolic pathways, including fatty acid oxidation and tricarboxylic acid cycle. Mitochondrial respiration was impaired at multiple states, along with lower levels of mitochondrial fission proteins Mfn1 and Mfn2. Cleavage of procaspase-1 suggested inflammasome formation. Assembly of inflammasomes with caspase-1 and NLRP3 was detected as shown by proximity ligation assay. Markers of neuroinflammation including microgliosis and elevated brain IL-1β expression were also observed. Importantly, these findings were further exacerbated in Sirt3−/− mice when fed a calorie-rich western diet. The observations of this study suggest that SIRT3 deficiency-induced brain mitochondrial dysfunction and neuroinflammation in metabolic syndrome may play a role in late-life cognitive decline.

Effects of Age at First Childbirth and Other Factors on Central Obesity in Postmenopausal Women: The 2013-2015 Korean National Health and Nutrition Examination Survey.

BackgroundWaist circumference is one of the key components of metabolic syndrome. Recent studies demonstrated that the reproductive profile was associated with metabolic syndrome in postmenopausal women. This study focused on the association between central obesity and age at first childbirth. It also considered other factors associated with central obesity in postmenopausal women.MethodsThis study was based on the 2013–2015 Korean National Health and Nutrition Examination Survey and involved 3,143 naturally postmenopausal women. These women were divided into three groups according to their age at first childbirth: 19 years or younger (n=252), 20–29 years (n=2,695), and 30 years or older (n=196). Multivariate analysis using logistic regression was performed to evaluate the effects of various reproductive factors, including other confounding factors.ResultsDuring adjustment for confounding factors, in the early age at first childbirth group, odds ratios (95% confidence intervals) for central obesity decreased. In the final model, younger age at first childbirth was not significantly related to central obesity (waist circumference more than 85 cm) in naturally postmenopausal women after adjusting for other confounding factors.ConclusionYounger age at first childbirth was not significantly associated with central obesity after adjustment for confounding factors.

Chemerin is not associated with subclinical atherosclerosis markers in prediabetes and diabetes.

Objective:Chemerin is a novel adipokine that is correlated with adipocyte differentiation, glucose metabolism, and inflammation. We aimed to investigate the relation between serum chemerin level and subclinical atherosclerosis markers as exemplified by brachial artery pulse wave velocity (baPWV), carotid intima–media thickness (CIMT), epicardial fat thickness (EFT), and carotid plaque presence in diabetes and prediabetes.Methods:Age-, body mass index (BMI)-, and gender-matched patients with type 2 DM (n=30), prediabetes (n=25), and normal glucose tolerance (n=25) were included in this cross-sectional study. Serum chemerin level, lipid parameters, glucose metabolism marker, baPWV, CIMT, EFT, and anthropometric were recorded. The independent risk factors for atherosclerosis markers were determined by linear and/or multiple logistic regression analysis.Results:baPWV and carotid plaque presence were higher in the diabetes group than in prediabetes and control groups (p=0.039 and p=0.035 respectively), whereas serum chemerin levels were similar among groups (p=0.338). Chemerin levels were not correlated with PWV, CIMT, and epicardial fat thickness overall or in the subgroups. Overall and in the diabetes group, chemerin levels were positively correlated with the key components of metabolic syndrome as BMI, total body fat percentage, waist circumference, triglyceride, and systolic and diastolic blood pressure (BP). After adjusting for age, gender, and BMI, only the association between chemerin and systolic BP remained significant. Chemerin was not found as an independent risk factor for predicting atherosclerosis in diabetes and prediabetes.Conclusion:Chemerin is not a predictive marker for atherosclerosis in diabetes and prediabetes, but correlates well with key aspects of the metabolic syndrome particularly in diabetes.

Study of metabolic syndrome in postmenopausal women

BACKGROUND: Various studies throughout the world have documented higher prevalence of Metabolic Syndrome (MS) and CV risk factors in postmenopausal women. Abdominal obesity, a key component of metabolic syndrome is quite prevalent in South Asian women. However, studies that have investigated the effect of menopause on the health status of Nepalese women is lacking. METHODS: This cross-sectional study was conducted in TUTH, Kathmandu Nepal. Forty five each premenopausal and postmenopausal (defined by cessation of menstruation for ≥12 months) women visiting the General Health Checkup Unit were enrolled as participants. Metabolic syndrome was defined by IDF criteria. BP, height, weight and WC were measured and BMI was calculated while fasting blood samples were analyzed for serum biochemical markers: FBG, lipid profile. RESULTS: This study found higher prevalence of MS in postmenopausal women (57.8%) in comparison to premenopausal women (20%). 13.3% were diabetic, 23.3% were hypertensive, 82.2% had abdominal obesity (WC&gt;80 cm), 43.3% were overweight (BMI 25-29.99 Kg/m2) and 13.3 % were obese (BMI≥30 Kg/m2). WC, BMI and SBP were significantly higher in postmenopausal group. Among the biochemical markers, FBG, TC, LDL-C, TG were significantly higher whereas HDL-C was significantly lower in postmenopausal women than in premenopausal women. CONCLUSION: MS was highly prevalent in postmenopausal women. This is an indication of taking necessary preventive measures so that the risk of developing diabetes and cardiovascular disease can be minimized in the postmenopausal group. DOI: http://dx.doi.org/10.3126/acclm.v1i1.12307 Ann. Clin. Chem. &amp; Lab. Med. 1(1) 2015: 6-11

Probing the factor structure of metabolic syndrome in Sardinian genetic isolates

Background and aimsOwing to the multiplicity of the key components of metabolic syndrome (MetS), its diagnosis is very complex. The lack of a unique definition is responsible for the prevalence variability observed among studies; therefore, a definition based on continuous variables was recommended. The aim of this study was to compare competing models of the MetS factor structure for selecting the one that explains the best clustering pattern and to propose an algorithm for computing MetS as a continuous variable. Methods and resultsData were from isolated Sardinian populations (n = 8102). Confirmatory factor analysis (CFA) and two-group CFA by gender were performed to evaluate the sex-specific factor structure of MetS. After selecting the best model, an algorithm was obtained using factor loadings/residual variances. The quality of the MetS score was evaluated by the receiver operating characteristics curve and the area under the curve. Cross-validation was performed to validate the score and to determine the best cut point. The best fit model was a bifactor one with a general factor (MetS) and three specific factors (f1: obesity/adiposity trait; f2: hypertension/blood pressure trait; and f3: lipid trait). Gender-specific algorithms were implemented to obtain MetS scores showing a good diagnostic performance (0.80 specificity and 0.80 sensitivity for the cut point). Furthermore, cross-validation confirmed these results. ConclusionThese analyses suggested that the bifactor model was the most representative one. In addition, they provided a score and a cut point that are both clinically accessible and interpretable measures for MetS diagnosis and likely useful for evaluating the association with adverse cardiovascular disease and diabetes and for investigating the MetS genetic component.

Intranasal Insulin Improves Age-Related Cognitive Deficits and Reverses Electrophysiological Correlates of Brain Aging.

Peripheral insulin resistance is a key component of metabolic syndrome associated with obesity, dyslipidemia, hypertension, and type 2 diabetes. While the impact of insulin resistance is well recognized in the periphery, it is also becoming apparent in the brain. Recent studies suggest that insulin resistance may be a factor in brain aging and Alzheimer's disease (AD) whereby intranasal insulin therapy, which delivers insulin to the brain, improves cognition and memory in AD patients. Here, we tested a clinically relevant delivery method to determine the impact of two forms of insulin, short-acting insulin lispro (Humalog) or long-acting insulin detemir (Levemir), on cognitive functions in aged F344 rats. We also explored insulin effects on the Ca(2+)-dependent hippocampal afterhyperpolarization (AHP), a well-characterized neurophysiological marker of aging which is increased in the aged, memory impaired animal. Low-dose intranasal insulin improved memory recall in aged animals such that their performance was similar to that seen in younger animals. Further, because ex vivo insulin also reduced the AHP, our results suggest that the AHP may be a novel cellular target of insulin in the brain, and improved cognitive performance following intranasal insulin therapy may be the result of insulin actions on the AHP.

Effects of Chinese herbal medicine Yiqi Huaju Qingli Formula in metabolic syndrome patients with microalbuminuria: a randomized placebo-controlled trial

Microalbuminuria (MAU) is a key component of metabolic syndrome (MetS) and is an early sign of diabetic nephropathy as well. Although routine Western medicine treatments are given to MetS patients to control high blood pressure, hyperglycemia and dyslipidemia, some patients still experience progressive renal lesions and it is necessary to modify and improve the treatment strategy for MetS patients. To investigate the efficacy of Yiqi Huaju Qingli Herb Formula, a compound traditional Chinese herbal medicine, in MetS patients with MAU when it is combined with routine Western medicine treatment. Sixty patients with MetS were randomized into the Chinese herbal formula group (CHF, Yiqi Huaju Qingli formula treatment in combination with Western medicine) and control group (placebo in combination with Western medicine). All treatments were administered for 12 weeks. Urinary microalbumin (MA), urinary albumin-to-creatinine ratio (UACR), 24-hour total urine protein (24-hTP), body mass index (BMI), waist circumference (WC), waist-to-hip ratio (WHR), fasting plasma glucose (FPG), 2-hour postprandial plasma glucose (2-hPPG), glycosylated hemoglobin (HbA1c), homeostasis model assessment for insulin resistance (HOMA-IR), blood lipid profile and blood pressure were observed. Compared with the control group, CHF treatment significantly decreased BMI (P<0.05), WC (P<0.01) and WHR (P<0.01). Both groups had significant decreases in FPG, 2-hPPG, HbA1c, HOMA-IR, MA, and UACR, with CHF treatment showing better effects on these parameters compared with the control treatment (P<0.05). Both treatments significantly reduced the levels of total cholesterol, low-density lipoprotein cholesterol and triacylglycerol (TAG), and a greater reduction in TAG was observed with CHF treatment (P<0.05). The level of high-density lipoprotein cholesterol did not change in the control group after treatment (P>0.05), whereas it significantly increased with CHF treatment (P<0.01). Compared with before the treatment, significant decreases in systolic blood pressure, diastolic blood pressure and mean arterial blood pressure were observed in both groups (P<0.01). However, there was no significant difference between the two groups (P>0.05). Combined treatment of Yiqi Huaju Qingli Formula and Western medicine significantly alleviated MAU, which may correlate with the improvement of insulin sensitivity and glucose and lipid metabolism. TRIAL REGISTRATION IDENTIFIER: This trial was registered in the Chinese Clinical Trial Registry with the identifier ChiCTR-TRC-11001633.

Adipose Angiotensinogen is Upregulated during Insulin Resistance in OLETF Rats

Activation of the renin‐angiotensin system (RAS) has been shown to contribute to metabolic syndrome. Hyptertension is a key component of metabolic syndrome and is regulated by RAS. The Otsuka Long‐Evans Tokushima Fatty (OLETF) rat is a relatively new and highly relevant model because its pathogenesis of insulin resistance, metabolic syndrome, and type 2 diabetes closely resembles that of the progression of the human condition. However, the contribution of adipose RAS to metabolic syndrome is not well defined. To address the hypothesis that adipose RAS activation is increased with insulin resistance, rats were divided into two groups (n=10–12/group): 1) lean strain‐control LETO and 2) obese insulin resistant OLETF. Systolic blood pressure (SBP) was measured weekly for 24 weeks and insulin resistance index (IRI) was determined at 9 and 24 weeks. Tissue samples were collected from each group (n=5–6/group) at 15 and 24 weeks. Mean SBP from OLETF was 28% and 27% greater compared to that of the LETO after 15 and 24 wk respectively. Mean IRI was greater at both time periods and was exacerbated in 24 wk OLETF compared to 15 wk. By 24 wk, adipose angiotensinogen (angiotensin precursor) expression had increased in 24 wk OLETF suggesting that activation of adipose RAS was increased. The data suggest that increased activation of adipose RAS may contribute to the increased metabolic disorders (SBP and IRI) commonly associated with metabolic syndrome.

A pilot study investigating the effect of Caralluma fimbriata extract on the risk factors of metabolic syndrome in overweight and obese subjects: a randomised controlled clinical trial

Central obesity is a key component of metabolic syndrome and it is often associated with other risk factors such as dyslipidemia, elevated plasma glucose levels and elevated blood pressure (BP). In this pilot study, the effect of Caralluma fimbriata (an edible succulent) extract in combination with controlled dietary intake and physical activity on these risk factors was assessed in overweight and obese Australian subjects. This was a randomised, double blind placebo controlled clinical trial. Forty-three adults aged 29-59 years were recruited. The eligibility criteria included a Body Mass Index (BMI) >25 kg/m(2), or a waist circumference >94 cm (male), >80 cm (female). Thirty-three participants completed the 12-week study at Victoria University Nutritional Therapy Clinic. Participants were randomly assigned into two groups. C. fimbriata extract and placebo were orally administered as 500 mg capsules twice daily (1 g/day) and dietary intake and exercise were monitored weekly. The results of thirty-three participants (experimental group, n = 17; placebo group n = 16) were analysed. The primary outcome measure was the decline in waist circumference. By week 9, the experimental group had lost 5.7 cm, compared to only 2.8 cm loss in the placebo group (Difference: -2.890; 95% CI; -5.802 to 0.023). Post intervention, the experimental group had lost 6.5 cm compared to 2.6 cm loss in the placebo group (Difference: -3.847; 95% CI; -7.466 to 0.228). Waist to hip ratio (WHR) also improved significantly after 12 weeks intervention in the experimental group, with a total reduction of 0.03 being recorded compared to 0.01 increase in the placebo group (Difference: -0.033; 95% CI; -0.064 to -0.002). There was also a significant decline in the palatability (visual appeal, smell, taste) of the test meal and sodium intake in the experimental group at week 12 (p < 0.05). In addition a significant reduction in body weight, BMI, hip circumference, systolic BP, HR, triglyceride levels, total fat and saturated fat intake within both groups was observed following the intervention period (p < 0.05). Supplementation with C. fimbriata extract whilst controlling overall dietary intake and physical activity may potentially play a role in curbing central obesity, the key component of metabolic syndrome. Controlling dietary intake and exercise improved body weight and favourably influenced the metabolic risk profile.

Identification of shared genetic susceptibility locus for coronary artery disease, type 2 diabetes and obesity: a meta-analysis of genome-wide studies

Type 2 diabetes (2DM), obesity, and coronary artery disease (CAD) are frequently coexisted being as key components of metabolic syndrome. Whether there is shared genetic background underlying these diseases remained unclear. We performed a meta-analysis of 35 genome screens for 2DM, 36 for obesity or body mass index (BMI)-defined obesity, and 21 for CAD using genome search meta-analysis (GSMA), which combines linkage results to identify regions with only weak evidence and provide genetic interactions among different diseases. For each study, 120 genomic bins of approximately 30 cM were defined and ranked according to the best linkage evidence within each bin. For each disease, bin 6.2 achieved genomic significanct evidence, and bin 9.3, 10.5, 16.3 reached suggestive level for 2DM. Bin 11.2 and 16.3, and bin 10.5 and 9.3, reached suggestive evidence for obesity and CAD respectively. In pooled all three diseases, bin 9.3 and 6.5 reached genomic significant and suggestive evidence respectively, being relatively much weaker for 2DM/CAD or 2DM/obesity or CAD/obesity. Further, genomewide significant evidence was observed of bin 16.3 and 4.5 for 2DM/obesity, which is decreased when CAD was added. These findings indicated that bin 9.3 and 6.5 are most likely to be shared by 2DM, obesity and CAD. And bin 16.3 and 4.5 are potentially common regions to 2DM and obesity only. The observed shared susceptibility regions imply a partly overlapping genetic aspects of disease development. Fine scanning of these regions will definitely identify more susceptibility genes and causal variants.

Negative Regulation of the Human Growth Hormone Gene by Insulin in Primary Pituitary Cell Cultures and a Possible Role for Hypoxia Inducible Factor (HIF)

Hyperinsulinemia is a key component of metabolic syndrome, and is associated with decreased growth hormone (GH) levels. There is evidence that the human (h) GH gene (hGH1) is a direct target for insulin. A hybrid reporter gene driven by upstream −496/+1 hGH1 sequences, including a putative insulin‐responsive HIF site, was negatively regulated by insulin in transfected tumor cells. Here, we have started to assess whether HIF is associated with insulin regulation of “endogenous” hGH1. In the absence of primary human pituitary cell cultures, transgenic (TG) mice expressing the intact hGH1 locus in a somatotroph‐specific manner were generated. Primary pituitary cell cultures from these TG mice were treated with or without 1–15 nM insulin. A significant decrease in hGH1 RNA levels was detected with a physiological dose of insulin. Stabilization of HIF protein by exposure to the hypoxia mimetic CoCl2 decreased hGH1 RNA levels significantly, and to the same extent as insulin treatment. The effects of inhibition of HIF synthesis by RNA interference, and HIF DNA binding by echinomycin treatment were also pursued. In both cases, the decrease in hGH1 RNA levels seen with insulin treatment was blocked significantly. These data indicate hGH1 RNA levels are regulated negatively by insulin, and that this effect is dependent on HIF protein/DNA binding.

The Leptin to Adiponectin Ratio is a Marker of the Number of Metabolic Syndrome Criteria in French Adults

Aim: Visceral distribution of adipose tissue (AT) is one of the key components of Metabolic Syndrome (MetS). Plasma concentrations of leptin and adiponectin are closely linked to AT distribution. Pulse wave velocity (PWV), a marker of arterial stiffness, is linked to metabolic syndrome and cardiovascular risk. The purpose of this study is to describe the extent of the usefulness of the Leptin/Adiponectin (L/A) ratio as a marker of MetS. Methods: Leptin and adiponectin concentrations, magnetic resonance image-based of visceral and subcutaneous fat measurements, and carotid PWV were analyzed in the subjects of a French prospective cohort composed of 97 subjects not presenting metabolic syndrome (MetS-), 122 patients with metabolic syndrome (MetS+) without diabetes, and 94 type 2 diabetics (T2D) with MetS. Results: After adjustment for gender and age, leptinemia was found to be higher in MetS+ patients than in T2D patients. Adiponectinemia alone was not discriminated. There was a statistically significant difference in the L/A ratio between MetS- patients and the other groups. For the whole population, there is a positive correlation between the L/A and waist circumference, waist-to-hip ratio, visceral fat (r=0.53), triglyceride concentrations, fasting glucose concentrations, insulinemia, systolic and diastolic blood pressure, and number of MetS criteria (r=0.39). The L/A ratio is also significantly correlated with carotid artery stiffness. Conclusion: This study demonstrates the potential usefulness of the L/A ratio as a marker, independent of age and gender, of a subject’s metabolic risk. The L/A Ratio is also a reliable marker for arterial stiffness.

Exercise ameliorates high-fat diet-induced metabolic and vascular dysfunction, and increases adipocyte progenitor cell population in brown adipose tissue.

A high-fat diet (HFD) is associated with adipose inflammation, which contributes to key components of metabolic syndrome, including obesity and insulin resistance. The increased visceral adipose tissue mass associated with obesity is the result of hyperplasia and hypertrophy of adipocytes. To investigate the effects of exercise on HFD-induced metabolic disorders, male C57BL/6 mice were divided into four groups: SED (sedentary)-ND (normal diet), EX (exercise)-ND, SED-HFD, and EX-HFD. Exercise was performed on a motorized treadmill at 15 m/min, 40 min/day, and 5 day/wk for 8 wk. Exercise resulted in a decrease in abdominal fat contents and inflammation, improvements in glucose tolerance and insulin resistance, and enhancement of vascular constriction and relaxation responses. Exercise with or without HFD increased putative brown adipocyte progenitor cells in brown adipose tissue compared with groups with the same diet, with an increase in brown adipocyte-specific gene expression in brown and white adipose tissue. Exercise training enhanced in vitro differentiation of the preadipocytes from brown adipose depots into brown adipocytes and enhanced the expression of uncoupling protein 1. These findings suggest that exercise ameliorates high-fat diet-induced metabolic disorders and vascular dysfunction, and increases adipose progenitor cell population in brown adipose tissue, which might thereby contribute to enhanced functional brown adipose.