Metabolic syndrome (MetS) was developed by the National Cholesterol Education Program Adult Treatment Panel III, identifying adults with at least 3 of 5 cardiometabolic risk factors (hyperglycemia, ...increased central adiposity, elevated triglycerides, decreased high-density lipoprotein cholesterol, and elevated blood pressure) who are at increased risk of diabetes and cardiovascular disease. The constellation of MetS component risk factors has a shared pathophysiology and many common treatment approaches grounded in lifestyle modification. Several attempts have been made to define MetS in the pediatric population. However, in children, the construct is difficult to define and has unclear implications for clinical care. In this Clinical Report, we focus on the importance of screening for and treating the individual risk factor components of MetS. Focusing attention on children with cardiometabolic risk factor clustering is emphasized over the need to define a pediatric MetS.
Abstract
Metabolic Syndrome and Associated Diseases: From the Bench to the Clinic, a Society of Toxicology Contemporary Concepts in Toxicology (CCT) workshop was held on March 11, 2017. The meeting ...was convened to raise awareness of metabolic syndrome and its associated diseases and serve as a melting pot with scientists of multiple disciplines (eg, toxicologists, clinicians, regulators) so as to spur research and understanding of this condition. The criteria for metabolic syndrome include obesity, dyslipidemia (low high-density lipoprotein and/or elevated triglycerides), elevated blood pressure, and alterations in glucose metabolism. It can lead to a greater potential of type 2 diabetes, lipid disorders, cardiovascular disease, hepatic steatosis, and other circulatory disorders. Although there are no approved drugs specifically for this syndrome, many drugs target diseases associated with this syndrome thus potentially increasing the likelihood of drug-drug interactions. There is currently significant research focusing on understanding the key pathways that control metabolism, which would be likely targets of risk factors (eg, exposure to xenobiotics, genetics) and lifestyle factors (eg, microbiome, nutrition, and exercise) that contribute to metabolic syndrome. Understanding these pathways could also lead to the development of pharmaceutical interventions. As individuals with metabolic syndrome have signs similar to that of toxic responses (eg, oxidative stress and inflammation) and organ dysfunction, these alterations should be taken into account in drug development. With the increasing frequency of metabolic syndrome in the general population, the idea of a “normal” individual may need to be redefined. This paper reports on the substance and outcomes of this workshop.
Metabolic syndrome (MetS) forms a cluster of metabolic dysregulations including insulin resistance, atherogenic dyslipidemia, central obesity, and hypertension. The pathogenesis of MetS encompasses ...multiple genetic and acquired entities that fall under the umbrella of insulin resistance and chronic low-grade inflammation. If left untreated, MetS is significantly associated with an increased risk of developing diabetes and cardiovascular diseases (CVDs). Given that CVDs constitute by far the leading cause of morbidity and mortality worldwide, it has become essential to investigate the role played by MetS in this context to reduce the heavy burden of the disease. As such, and while MetS relatively constitutes a novel clinical entity, the extent of research about the disease has been exponentially growing in the past few decades. However, many aspects of this clinical entity are still not completely understood, and many questions remain unanswered to date. In this review, we provide a historical background and highlight the epidemiology of MetS. We also discuss the current and latest knowledge about the histopathology and pathophysiology of the disease. Finally, we summarize the most recent updates about the management and the prevention of this clinical syndrome.
Diabetic peripheral neuropathy and metabolic syndrome (MetS) are both global health challenges with well‐established diagnostic criteria and significant impacts on quality of life. Clinical ...observations, epidemiologic evidence, and animal models of disease have strongly suggested MetS is associated with an elevated risk for cryptogenic sensory peripheral neuropathy (CSPN). MetS neuropathy preferentially affects small unmyelinated axons early in its course, and it may also affect autonomic and large fibers. CSPN risk is linked to MetS and several of its components including obesity, dyslipidemia, and prediabetes. MetS also increases neuropathy risk in patients with established type 1 and type 2 diabetes. In this review we present animal data regarding the role of inflammation and dyslipidemia in MetS neuropathy pathogenesis. Several studies suggest exercise‐based lifestyle modification is a promising treatment approach for MetS neuropathy.
Metabolic syndrome Samson, Susan L; Garber, Alan J
Endocrinology and metabolism clinics of North America,
03/2014, Volume:
43, Issue:
1
Journal Article
Peer reviewed
Metabolic syndrome is not a disease per se, but is a term that highlights traits that may have an increased risk of disease, approximately 2-fold for cardiovascular disease and 5-fold or more for ...type 2 diabetes mellitus. Obesity and insulin resistance are believed to be at the core of most cases of metabolic syndrome, although further research is required to truly understand the pathophysiology behind the syndrome and the gene-environment interactions that increase susceptibility. The mainstay of treatment remains lifestyle changes with exercise and diet to induce weight loss and pharmacologic intervention to treat atherogenic dyslipidemia, hypertension, and hyperglycemia.
While activation of beige thermogenesis is a promising approach for treatment of obesity-associated diseases, there are currently no known pharmacological means of inducing beiging in humans. ...Intermittent fasting is an effective and natural strategy for weight control, but the mechanism for its efficacy is poorly understood. Here, we show that an every-other-day fasting (EODF) regimen selectively stimulates beige fat development within white adipose tissue and dramatically ameliorates obesity, insulin resistance, and hepatic steatosis. EODF treatment results in a shift in the gut microbiota composition leading to elevation of the fermentation products acetate and lactate and to the selective upregulation of monocarboxylate transporter 1 expression in beige cells. Microbiota-depleted mice are resistance to EODF-induced beiging, while transplantation of the microbiota from EODF-treated mice to microbiota-depleted mice activates beiging and improves metabolic homeostasis. These findings provide a new gut-microbiota-driven mechanism for activating adipose tissue browning and treating metabolic diseases.
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•EODF is a novel strategy for beige adipose development•EODF selectively induces WAT beiging by reshaping gut microbiota•EODF reverses high-fat-diet-induced obesity and associated metabolic disorders•The microbiota-fat axis orchestrates EODF-induced metabolic improvement
White adipose beiging is a promising therapy for obesity and related metabolic diseases. Here, Li, Xie and colleagues find that an EODF regimen can selectively induce the beiging of white adipose tissue and subsequently ameliorate metabolic disorders in mice. Gut microbiota orchestrate the effects of EODF on beiging and metabolic improvement.
The world wide prevalence of obesity and the metabolic syndrome is escalating. Contrary to earlier experimental evidence, human obesity is characterised by sympathetic nervous activation, with the ...outflows to both the kidney and skeletal muscle being activated. While the mechanisms responsible for initiating the sympathetic activation remain to be unequivocally elucidated, hyperinsulinemia, obstructive sleep apnoea, increased circulating adipokines, stress and beta adrenergic receptor polymorphisms are implicated. The pattern of sympathetic activation may be the pathophysiological mechanism underpinning much obesity-related illnesses with the consequences including, amongst others, the development of hypertension, insulin resistance, diastolic dysfunction and renal impairment. While diet and exercise are the first line therapy for the treatment of obesity and the metabolic syndrome, pharmacological interventions targeting the sympathetic nervous system, either directly or indirectly are also likely to be of benefit. Importantly, the benefit may not necessarily be weight related but may be associated with a reduction in end organ damage.
The long-term impact of intentional weight loss on cardiovascular events remains unknown. We describe 12-month changes in body weight and cardiovascular risk factors in PREvención con DIeta ...MEDiterránea (PREDIMED)-Plus, a trial designed to evaluate the long-term effectiveness of an intensive weight loss lifestyle intervention on primary cardiovascular prevention.
Overweight/obese adults with metabolic syndrome aged 55-75 years (
= 626) were randomized to an intensive weight loss lifestyle intervention based on an energy-restricted Mediterranean diet, physical activity promotion, and behavioral support (IG) or a control group (CG). The primary and secondary outcomes were changes in weight and cardiovascular risk markers, respectively.
Diet and physical activity changes were in the expected direction, with significant improvements in IG versus CG. After 12 months, IG participants lost an average of 3.2 kg vs. 0.7 kg in the CG (
< 0.001), a mean difference of -2.5 kg (95% CI -3.1 to -1.9). Weight loss ≥5% occurred in 33.7% of IG participants compared with 11.9% in the CG (
< 0.001). Compared with the CG, cardiovascular risk factors, including waist circumference, fasting glucose, triglycerides, and HDL cholesterol, significantly improved in IG participants (
< 0.002). Reductions in insulin resistance, HbA
, and circulating levels of leptin, interleukin-18, and MCP-1 were greater in IG than CG participants (
< 0.05). IG participants with prediabetes/diabetes significantly improved glycemic control and insulin sensitivity, along with triglycerides and HDL cholesterol levels compared with their CG counterparts.
PREDIMED-Plus intensive lifestyle intervention for 12 months was effective in decreasing adiposity and improving cardiovascular risk factors in overweight/obese older adults with metabolic syndrome, as well as in individuals with or at risk for diabetes.
Dysregulation of circadian rhythms is associated with metabolic dysfunction, yet it is unclear whether enhancing clock function can ameliorate metabolic disorders. In an unbiased chemical screen ...using fibroblasts expressing PER2::Luc, we identified Nobiletin (NOB), a natural polymethoxylated flavone, as a clock amplitude-enhancing small molecule. When administered to diet-induced obese (DIO) mice, NOB strongly counteracted metabolic syndrome and augmented energy expenditure and locomotor activity in a Clock gene-dependent manner. In db/db mutant mice, the clock is also required for the mitigating effects of NOB on metabolic disorders. In DIO mouse liver, NOB enhanced clock protein levels and elicited pronounced gene expression remodeling. We identified retinoid acid receptor-related orphan receptors as direct targets of NOB, revealing a pharmacological intervention that enhances circadian rhythms to combat metabolic disease via the circadian gene network.
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•High-throughput screening identified Nobiletin as a clock amplitude enhancer•Nobiletin potently protects against metabolic syndrome in a clock-dependent manner•Nobiletin remodels circadian and metabolic gene expression•Nobiletin is an agonist for the ROR nuclear receptors in the circadian oscillator
In a high-throughput chemical screen, He et al. identify the small molecule Nobiletin (NOB), a naturally occurring compound enriched in citrus peels, as a circadian clock amplitude enhancer, which protects against metabolic disease. NOB is an agonist for the ROR nuclear receptors in the circadian oscillator.
Dietary lipids favor the growth of the pathobiont Bilophila wadsworthia, but the relevance of this expansion in metabolic syndrome pathogenesis is poorly understood. Here, we showed that B. ...wadsworthia synergizes with high fat diet (HFD) to promote higher inflammation, intestinal barrier dysfunction and bile acid dysmetabolism, leading to higher glucose dysmetabolism and hepatic steatosis. Host-microbiota transcriptomics analysis reveal pathways, particularly butanoate metabolism, which may underlie the metabolic effects mediated by B. wadsworthia. Pharmacological suppression of B. wadsworthia-associated inflammation demonstrate the bacterium's intrinsic capacity to induce a negative impact on glycemic control and hepatic function. Administration of the probiotic Lactobacillus rhamnosus CNCM I-3690 limits B. wadsworthia-induced immune and metabolic impairment by limiting its expansion, reducing inflammation and reinforcing intestinal barrier. Our results suggest a new avenue for interventions against western diet-driven inflammatory and metabolic diseases.
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