Oxidative stress as pathogenesis of cardiovascular risk associated with metabolic syndrome

Metabolic syndrome (MetS) is characterized by accumulation of visceral fat associated with the clustering of metabolic and pathophysiological cardiovascular risk factors: impaired glucose tolerance, dyslipidemia, and hypertension. Although the definition of MetS is different among countries, visceral obesity is an indispensable component of MetS. A growing body of evidence suggests that increased oxidative stress to adipocytes is central to the pathogenesis of cardiovascular disease in MetS. Increased oxidative stress to adipocytes causes dysregulated expression of inflammation-related adipocytokines in MetS, which contributes to obesity-associated vasculopathy and cardiovascular risk primarily through endothelial dysfunction. The purpose of present review is to unravel the mechanistic link between oxidative stress and cardiovascular risk in MetS, focusing on insulin resistance, hypertension, and atherosclerosis. Then, therapeutic opportunities translated from the bench to bedside will be provided to develop novel strategies to cardiovascular risk factors in MetS.     

Associations of visceral fat,physical activity and muscle strength with the metabolic syndrome

Objective

We investigated the association of visceral fat with the metabolic syndrome (MetS) and its separate components; the associations of both physical activity and muscle strength with the MetS and its separate components independent of visceral fat. Furthermore, we studied these associations within participants with low and high amounts of visceral fat.

Study design

400 men (aged 40–80 years) were recruited into a cross-sectional study.Main outcome measures: Logistic regression models were used to study the individual associations in all participants (OR). The associations of physical activity (active vs inactive) and muscle strength (high vs low) within participants with low and high levels of visceral fat (assessed by ultrasonography) were tested using Univariate Analysis of Variance (difference in mean levels of the separate components of MetS) and logistic regression (risk on MetS).

Results

High levels of visceral fat were significantly associated with increased risk of MetS (OR 1.7 95%CI 1.5;1.9) and its separate components (p < 0.05). We did not find strong individual associations for physical activity or muscle strength, neither within men with low or high levels of visceral fat.

Conclusions

High body fat levels were associated with an unhealthier metabolic risk profile and a higher risk of the MetS. Our cross-sectional data do not indicate associations for physical activity or for muscle strength with the MetS independent of visceral fat. Also no differential associations of physical activity or muscle strength in men with low or high levels of visceral fat were found.     

Should visceral fat be reduced to increase longevity?

Several epidemiologic studies have implicated visceral fat as a major risk factor for insulin resistance, type 2 diabetes mellitus, cardiovascular disease, stroke, metabolic syndrome and death. Utilizing novel models of visceral obesity, numerous studies have demonstrated that the relationship between visceral fat and longevity is causal while the accrual of subcutaneous fat does not appear to play an important role in the etiology of disease risk. Specific recommended intake levels vary based on a number of factors, including current weight, activity levels, and weight loss goals. It is discussed the need of reducing the visceral fat as a potential treatment strategy to prevent or delay age-related diseases and to increase longevity.     

Melatonin and the metabolic syndrome: a tool for effective therapy in obesity‐associated abnormalities?

The metabolic syndrome (MetS) is a cluster of metabolic abnormalities associated with increased risk for cardiovascular diseases. Apart from its powerful antioxidant properties, the pineal gland hormone melatonin has recently attracted the interest of various investigators as a multifunctional molecule. Melatonin has been shown to have beneficial effects in cardiovascular disorders including ischaemic heart disease and hypertension. However, its role in cardiovascular risk factors including obesity and other related metabolic abnormalities is not yet established, particularly in humans. New emerging data show that melatonin may play an important role in body weight regulation and energy metabolism. This review will address the role of melatonin in the MetS focusing on its effects in obesity, insulin resistance and leptin resistance. The overall findings suggest that melatonin should be exploited as a therapeutic tool to prevent or reverse the harmful effects of obesity and its related metabolic disorders.     

Hyperinsulinaemia, a key factor of the metabolic syndrome in postmenopausal women

The metabolic syndrome (MetS) is a complex disorder combining obesity, hypertension, atherogenic dyslipidaemia and insulin resistance, a clustering of factors which markedly enhance the risk of developing cardiovascular disease (CVD) and type 2 diabetes. Main features of the MetS, which are found in many postmenopausal women, are increasing prevalence of insulin resistance and obesity (particularly visceral adiposity). Accordingly, a majority of postmenopausal women comply with criteria defining the MetS, and CVD is the first cause of morbidity/mortality in women, occurring even more frequently than in men. Moreover, obesity-related type 2 diabetes approaches pandemic proportions. Simultaneous occurrence of insulin resistance and obesity are most detrimental for metabolic health, and are also associated with increased oxidative stress, inflammatory and prothrombotic processes as well as with postmenopausal alterations in adipocytokine production. Hormone replacement therapy, provided the selected progestin does not antagonize estrogen action, may improve fat mass and distribution, dyslipidaemia and insulin sensitivity in postmenopausal women.     

The metabolic syndrome: the crossroads between rheumatoid arthritis and cardiovascular risk

Rheumatoid arthritis (RA) patients have an incidence of cardiovascular (CV) diseases at least two times higher than the general population. Atherosclerosis, the main determinant of CV morbidity and mortality, and carotid intima-media thickness, an early preclinical marker of atherosclerosis, also occur early on in RA. Traditional CV risk factors seem to have the same prevalence in RA and non-RA patients, and thus do not fully explain the increased CV burden, suggesting that RA inflammation and therapies play a role in increasing CV risk in these patients. The metabolic syndrome and fat tissue are likely to be the major players in this complex network. The metabolic syndrome (MetS) represents a cluster of cardiovascular risk factors that have in common insulin resistance and increased visceral adiposity. This entity has received great attention in the last few years due to its contribution to the burden of cardiovascular morbidity and mortality. Moreover, recently the adipose tissue has emerged as a dynamic organ that releases several inflammatory and immune mediators (adipokines). The association of MetS and atherosclerosis is thought to be partly mediated by altered secretion of adipokines by the adipose tissue and, on the other hand, there are evidence that adipokines may play some role in inflammatory arthritides. Obesity is now regarded as a systemic, low-grade inflammatory state, and inflammation as a link between obesity, metabolic syndrome, and cardiovascular diseases. To obtain a full control of the CV risk, data suggest that it is therefore mandatory a "tight control" of both RA and MetS inflammations.     

Independent associations of body-size adjusted fat mass and fat-free mass with the metabolic syndrome in Chinese

Background: Excess fat leads to adverse health outcomes. Most previous studies investigating body fatness using BMI or fat percentage, which contain both fat mass and fat-free mass, were not able to differentiate the exposure.

Aim: The present study assessed the independent association of fat and fat-free mass with metabolic syndrome (MetS) in Chinese.

Subjects and methods: A population-based study of 1144 subjects aged 50–70 from urban and rural areas of Shanghai in 2005–2006 was employed. Body composition was measured with DEXA. Fat mass index (FMI) and fat-free mass index (FFMI) were calculated. MetS was defined using the National Cholesterol Education Program Adult Treatment Panel III (NCEP ATP III) criteria without waist circumference for its high correlation with body composition.

Results: Both FMI and FFMI were significantly related with higher odds of MetS (OR 3.97, 95% CI 2.58–6.09 for FMI; OR 2.67, 95% CI 1.70–4.18 for FFMI, the highest quartile vs the lowest group) after adjusting for age, residence, sex, smoking, drinking, physical activity, medication, family history of chronic diseases, and fat-free mass (for FMI) or fat mass (for FFMI).

Conclusion: Both FMI and FFMI are independently associated with increased MetS risks. Proper expression of body composition is essential in assessing body composition and disease risk association.     

Metabolic syndrome and systemic lupus erythematosus: the connection

ABSTRACT

Introduction: The metabolic syndrome (MetS) is now recognized as a chronic proinflammatory and prothrombotic state that aggravates insulin resistance, oxidative injury, and cardiovascular risk. MetS is more prevalent in patients with systemic lupus erythematosus (SLE), a prototype of systemic autoimmune disease associated with premature atherosclerosis that cannot be accounted by traditional vascular risk factors alone. Dysregulation of the cytokines and adipokines is a common feature in both SLE and MetS, suggesting a complex relationship among autoimmunity, obesity, inflammation, and atherosclerosis.

Areas covered: This review summarizes the prevalence of MetS and its effect on cardiovascular outcome and organ damage in patients with SLE. The pathophysiology of MetS and its relevance to SLE is also briefly discussed.

Expert opinion: Imbalance of adipokine production in MetS contributes to inflammation and atherosclerosis. MetS predisposes SLE patients to new cardiovascular events and vascular mortality, as well as the development of chronic kidney disease and diabetes mellitus. However, conflicting results have been reported in the literature regarding the levels of the proinflammatory leptin and anti-inflammatory adiponectin, and their relationship with disease activity in SLE patients. While lifestyle modifications and targeting dyslipidemia, hypertension and diabetes mellitus is essential, there is little information on the efficacy and safety of metformin and hydroxychloroquine in alleviating insulin resistance in SLE or MetS. Further research on adipokines in SLE and the role of anti-obesity medications and probiotics in MetS is necessary.     

Ten-Year Trends of Metabolic Syndrome Prevalence and Nutrient Intake among Korean Children and Adolescents: A Population-Based Study

PurposeMetabolic syndrome (MetS) comprises a cluster of risk factors for future cardiovascular and metabolic diseases. Only a few recent studies have reported the trend in the prevalence of MetS in youth. This study aimed to analyze trends in the prevalence of MetS and nutrient intake in the last 10 years and investigate the changes in MetS components among Korean children and adolescents.Materials and MethodsWe analyzed the data of 9513 children and adolescents aged 10–19 years from the 2008–2017 Korean National Health and Nutrition Examination Surveys. Diagnosis of MetS was based on the International Diabetes Federation (IDF) and modified National Cholesterol Education Program-Adult Treatment Panel III (NCEP-ATP III) criteria.ResultsBased on the IDF criteria, MetS prevalence increased from 1.53% in 2008 to 3.19% in 2017 (p=0.007). Based on the NCEP-ATP III criteria, MetS prevalence increased from 2.18% in 2008 to 3.19% in 2017; however, the increase was not statistically significant. Daily calorie and fat intakes increased significantly during the study period. Among the risk factors that MetS comprises, the prevalence rates of central obesity, low high-density lipoprotein cholesterol levels, and high fasting glucose levels increased significantly.ConclusionOver the last 10 years, the prevalence of MetS has grown significantly with increasing calorie and fat intake in Korean children and adolescents. Central obesity and high-density lipoprotein cholesterol and fasting glucose levels have worsened. Therefore, active support and close monitoring are required to control MetS and prevent further increase in the prevalence of cardiovascular diseases.     

High prevalence of cardiometabolic risk features in adolescents with 47,XXY/Klinefelter syndrome

Klinefelter syndrome (KS) occurs in 1:600 males and is associated with high morbidity and mortality due to diabetes and cardiovascular disease. Up to 50% of men with KS have metabolic syndrome, a cluster of features conferring increased risk for diabetes and cardiovascular disease. These cardiometabolic (CM) risk features have not been studied in adolescents with KS. The objective of this cohort study was to compare CM risk features in adolescents with KS to controls matched for sex, age, and BMI z score. Fifty males with KS (age 10–17 years) were well‐matched to male controls (n = 50) for age (14.0 ± 1.7 vs. 14.0 ± 1.5 years) and BMI z score (0.3 ± 1.3 vs. 0.4 ± 1.2). Three CM risk features were present in 30% of adolescents with KS compared to 12% of controls (RR 2.5, 95% CI 1.1–5.9, p = .048). The KS group had significantly lower HDL cholesterol (p = .006), higher triglycerides (p < .001), and greater waist circumference percentile (p < .001). Despite a normal BMI, the prevalence of CM risk features was very high in adolescents with KS, particularly for central adiposity and dyslipidemia. The pathophysiology of this metabolic profile independent of obesity needs further investigation to facilitate prevention of the high morbidity of cardiovascular disease and diabetes in this population. ClinicalTrials.gov identifiers: NCT01585831 and NCT02723305.     

Effects of different types of exercise on body composition and fat distribution in HIV-infected patients: a brief review.

HIV infection and its treatment is associated with unfavourable metabolic and morphological abnormalities. These metabolic abnormalities, particularly alterations in body composition and fat distribution, may increase the risk for cardiovascular and metabolic complications, as well as reduce functional independence and lower self-esteem. Thus there is an urgent need to develop interventions intended to manage secondary side effects of HIV or antiretroviral therapy-related complications. In poly-treated patients, nonpharmacological interventions are a logical first step. Exercise training in particular may help alleviate some of the metabolic adverse effects associated with antiretroviral therapy by favourably altering body composition and patterns of body fat distribution. Studies have shown that exercise training, particularly aerobic training, can help reduce total body and visceral fat, as well as normalizing lipid profiles in HIV-infected patients. The results for resistance training, however, are less conclusive. Knowledge of the use of resistance and aerobic training and its attendant effects on insulin resistance and adipocytokines may represent an effective nonpharmacologic means for treating metabolic complications of HIV-infected persons who are receiving appropriate antiretroviral therapy. In this brief review we examine the effects of aerobic and resistance training on body composition, body fat distribution, and selected metabolic outcomes.     

身体活动与运动对代谢综合征的影响与作用

文题释义： 代谢综合征：是指遗传和环境因素共同所致人体的蛋白质、脂肪、碳水化合物等物质发生代谢紊乱的病理状态,是多个心脑血管危险因素集聚于同一个体的慢性症候群,其可分为中心性肥胖、血脂紊乱、高血压、糖尿病或糖耐量异常等多种代谢性疾病,是导致糖尿病及心血管等疾病的危险因素。 身体活动与运动：身体活动与运动是不同的概念,身体活动是由骨骼肌收缩引起能量代谢的任何机体活动,即潜在表现在人们的生活、劳动、学习等方面;体育运动则是为了保持一种或几种身体能力而进行的有计划、有组织、重复性的身体活动。 背景：目前,代谢综合征呈现出“高龄化”和“低龄化”两大趋势。增加身体活动量和积极运动能有效提高代谢综合征患者的胰岛素敏感度,调节机体脂代谢和糖代谢,以及有降血压的作用,降低代谢综合征发病率。 目的：全面评述身体活动及运动介入对代谢综合征的影响作用,进一步揭示身体活动、有氧运动、抗阻运动等对儿童青少年和中老年人代谢综合征产生的正向效益,从而为有效预防、缓解及治疗代谢综合征提供理论及实践参考。 方法：利用PubMed、ElsevierSDOL以及CNKI等中、英文资料数据库,以 “代谢综合征”“身体活动” “运动”等中英主题词搜索研究文献,关键词主要有“代谢综合征、身体活动、运动”“Metabolic syndrome, physical activity, exercise”。针对代谢综合征发病机制及身体活动和运动对代谢综合征的影响等进行归纳、整理,以确保最终入围的文献符合研究目的。 结果与结论：①充分的身体活动是代谢综合征的保护独立因素,少坐多动、改变出行方式、增加家务活动等健康的生活方式能有效加快能量代谢,提高各人群胰岛素敏感度,降低代谢综合征及各个组分疾病的患病率;②规律运动对防治代谢综合征具有显著正向效益,有氧运动与抗阻运动均可降低机体脂含量及胰岛素抵抗等危险因素;其中抗阻运动在增加骨骼肌含量、提升基础代谢率和胰岛素敏感度,控制血糖效果更为显著;但仅有氧运动可纠正代谢综合征的炎症反应,并在减少体脂和降血压方面更有优势;③儿童、青少年肥胖与代谢综合征密切相关,身体活动及运动对预防及改善代谢综合征有显著作用,而代谢综合征的改善则可控制儿童及青少年肥胖,从而有利于减少其成年后发病率;中老年代谢综合征患者生存率降低,血管粥样硬化及心脑血管疾病发病风险及死亡率升高,生活方式的转变及规律运动是防治中老年代谢综合征及心脑血管疾病发生的重要举措。 ORCID: 0000-0002-9648-5510(田露) 中国组织工程研究杂志出版内容重点：组织构建;骨细胞;软骨细胞;细胞培养;成纤维细胞;血管内皮细胞;骨质疏松;组织工程     

Vitamin D and menopause—A narrative review

There is accumulating evidence that vitamin D (VD) has important effects besides its well-known role in calcium and bone metabolism. Hypovitaminosis D is associated with cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, cancer as well as with increased mortality. Further, VD deficiency is related to depression and impaired cognitive function. Increasing age and elevated body fat mass contribute to an increased risk of VD deficiency. Further, some studies report a relationship between VD and estrogen metabolism.     

Regional differences of insulin action in adipose tissue: insights from in vivo and in vitro studies

Adipose tissue is now recognized to have a multitude of functions that are of importance in the regulation of energy balance and substrate metabolism. Different hormones, in particular insulin and catecholamines, govern the storage and utilization of energy in the triglyceride depots. In addition, adipocytes produce several different substances with endocrine or paracrine functions, which regulate the overall energetic homeostasis. With excess energy storage, obesity develops, leading to increased risk for type 2 diabetes and cardiovascular disease. The distribution of body fat appears to be even more important than the total amount of fat. Abdominal and, in particular, visceral adiposity is strongly linked to insulin resistance, type 2 diabetes, hypertension and dyslipidaemia, leading to increased risk of cardiovascular disease. The adverse metabolic impact of visceral fat has been attributed to distinct biological properties of adipocytes in this depot compared with other adipose tissue depots. Indeed, regional variations in the metabolic activity of fat cells have been observed. Furthermore, expression studies aiming at defining the unique biological properties of adipose tissues from distinct anatomical sites have identified depot-related differences in the protein content of fat-produced molecules. In this review we wish to summarize important results from the literature and also some recent data from our own work. The main scope is to describe the biological functions of adipose tissue, and to focus on metabolic, hormonal, and signalling differences between fat depots.     

Antioxidant-Rich Dietary Intervention Improves Cardiometabolic Profiles and Arterial Stiffness in Elderly Koreans with Metabolic Syndrome

PurposeOxidative stress plays an important role in the pathogenesis of chronic metabolic diseases. This study investigated the effect of the antioxidant-rich dietary intervention on oxidative stress, metabolic parameters, and arterial stiffness in elderly Koreans with metabolic syndrome (MetS).Materials and MethodsThirty-one subjects with MetS were enrolled and randomly divided into dietary intervention group and control group. Subjects in the intervention group received three meal boxes prepared with antioxidant-rich ingredients every day for 4 weeks, and subjects in the control group maintained their usual diets. Anthropometric and various biochemical parameters related to oxidative stress, inflammation, and MetS were assessed. Brachial-ankle pulse wave velocity (baPWV) and fat measurement using computed tomography were also conducted before and after 4 weeks.ResultsThere were significant differences in waist circumference, visceral to subcutaneous fat ratio, lipid peroxidation, oxidized low density lipoprotein (oxLDL), systolic and diastolic blood pressure, lipid parameters, advanced glycation end products, and baPWV between before and after the study in the experimental group (all p<0.05). Significant inter-group differences were observed between the experimental and control group in terms of the differences in body mass index, waist circumference, oxygen radical absorbance capacity, protein carboxylation, lipid peroxidation, oxLDL, blood pressure, lipid parameters, and baPWV between before and after the study (all p<0.05).ConclusionAntioxidant-rich dietary intervention for a 4-week period ameliorated the state of oxidative stress and improved the components of MetS including central obesity, dyslipidemia, hypertension, and arterial stiffness in elderly Koreans with MetS.     

Cardiometabolic health in Turner syndrome

Individuals with Turner syndrome (TS) have a higher morbidity and mortality compared to the general population. Diabetes and cardiovascular disease are the major contributors to this burden. Precursors to diabetes and cardiovascular disease make up what is known as metabolic syndrome, including abdominal obesity, hypertension, dyslipidemia, and elevated fasting glucose. These features of poor cardiometabolic health are also prevalent among women with TS. Youth with TS also exhibit many of these features, indicating that the pathogenesis of these cardiometabolic conditions may begin early in life. The etiology of the increased risk of cardiometabolic conditions in TS is likely multifactorial, involving genetics, epigenetics, hypogonadism, medical comorbidities, medications, and lifestyle. Counseling for the increased risk of cardiometabolic diseases as well as efforts to prevent or lower this risk should be routinely provided in the care of all patients with TS. Clinical practice guidelines are now available to guide screening and treatment of cardiometabolic conditions in girls and women with TS.     

Cardiorespiratory fitness effect may be under-estimated in ‘fat but fit’ hypothesis studies

Background: Both cardiorespiratory fitness and body fat have been independently related to metabolic syndrome in adolescents; however, the strength of these relationships seems to be dependent on the outcome composition.

Aim: To analyse the relationship between cardiorespiratory fitness and body fat combined with different indicators of metabolic risk in adolescents.

Subjects and methods: The sample was composed of 957 adolescents (58.7% girls). Cardiorespiratory fitness was obtained using the 20-metre shuttle run test and skinfold thickness was collected for body fat estimation. Metabolic risk score was calculated from waist circumference, systolic and diastolic blood pressure, glucose, HDL cholesterol and triglycerides measurements and an alternative outcome without the central obesity indicator was adopted. Chronological age and somatic maturity were used as covariates.

Results: Higher metabolic risk was observed in the highest fat/lowest fit adolescents (p?Conclusion: These findings suggest that body fat is strongly related to cardiovascular risk, but, when the outcome is calculated without the central obesity indicator, cardiorespiratory fitness becomes more related to metabolic risk.     

Evaluation of Lasting High Levels of CRP among the Patients with Metabolic Syndrome

“Low-grade” systemic inflammation is common findings in patients with metabolic syndrome (MetS). When we assessed 256 MetS patients, we found eight patients who presented high levels of C-reactive protein (CRP) which are between 40 and 15 mg/L for more than 3 years. They have not satisfied any criteria of inflammatory diseases such as rheumatoid arthritis and the area of visceral fat estimated by computed tomography was more than 200 cm². All the other MetS patients of visceral fat over 200 cm² presented low levels of CRP which are less than 10 mg/L. Insulin resistance and ultrasound study of carotid plaques showed no differences between high and low levels of CRP patients. There are a series of MetS patients who show high levels of CRP without clinical symptoms of inflammatory diseases. High levels of CRP merely cannot be explained by visceral fat area, insulin resistance, or carotid plaques.     

Impact of visceral fat on the metabolic syndrome and nonalcoholic fatty liver disease

Visceral fat has been reported to be associated with nonalcoholic fatty liver disease (NAFLD) and the metabolic syndrome (MetS). We assessed the prevalence of both NAFLD and the MetS, measured visceral fat thickness VFT), and estimated the physical activity indexes of 224 relatively healthy hospital workers. We also investigated the associations between both VFT and physical activity index and each of NAFLD and the MetS. The MetS was diagnosed according to the guidelines outlined by the Adult Treatment Panel III, and NAFLD was diagnosed by ultrasonography. Subjects with hepatitis B and C infections and those reporting moderate alcohol consumption were excluded from the study. The prevalence of the MetS was 11.6% and that of NAFLD was 41.5%. Many subjects with the MetS had NAFLD (73.1%), and some subjects with NAFLD (20.4%) also had several components of the MetS (p=0.001). VFT was significantly increased by both the addition of components of the MetS and the severity of NAFLD (p<0.001). In addition, VFT was independently associated with NAFLD (odds ratio [OR], 1.10; 95% confidence interval [CI], 1.02-1.19) in subjects with more than 2 components of the MetS. In contrast, habitual physical activity was reversely associated with NAFLD (OR, 0.29; 95% CI, 0.10-0.87). In conclusion, an increased visceral fat content and reduced physical activity could be not only biological markers but also therapeutic targets in the treatment of NAFLD and the MetS.     

Clinical aspects of obesity in the gynecological endocrinologicaly practice

Obesity is epidemic of 21st century, its visceral form is associated with increased risk for type 2 diabetes, cardiovascular disease, hypertension and increased mortality due to consequences of the disease. This type of obesity is a common diagnostic and therapeutic problem in gynecological practice. This especially concerns polycystic ovary disease, in which this type of obesity with its metabolic consequences is one of the important factors in etiology and additionally may lead to remote metabolic and cardiovascular problems. Another group of women in which this type of obesity plays an important role are climacteric women in whom redistribution of adipose tissue with increase in visceral fat deposit occurs. On the basis of current viewpoints and own experiences, the authors propose a diagnostic-therapeutic algorithm in women with visceral obesity and polycystic ovary disease or climacteric period. In case with cardiovascular risk factors (waist circumference over than 80cm, serum triglycerides over 1.7mmol/l, HDL cholesterol lower than 1.0mmol/l, blood pressure over 130/85mmHg and fast serum glucose levels over 100mg/dl) the therapeutic model focuses on the recognize risk factors. It must be considered that diet and physical activity play a very important role in the therapy.