Showing papers on "Insulin resistance published in 2017"
TL;DR: The data support the argument that magnesium supplementation improves the metabolic status in hypomagnesemic CKD patients with pre-diabetes and obesity.
Abstract: Background/Aims: Magnesium is an essential mineral for many metabolic functions. There is very little information on the effect of magnesium supplementation on me
4,639 citations
TL;DR: Detailed metabolic phenotyping of obese persons will be invaluable in understanding the pathophysiology of metabolic disturbances, and is needed to identify high-risk individuals or subgroups, thereby paving the way for optimization of prevention and treatment strategies to combat cardiometabolic diseases.
Abstract: The current obesity epidemic poses a major public health issue since obesity predisposes towards several chronic diseases BMI and total adiposity are positively correlated with cardiometabolic disease risk at the population level However, body fat distribution and an impaired adipose tissue function, rather than total fat mass, better predict insulin resistance and related complications at the individual level Adipose tissue dysfunction is determined by an impaired adipose tissue expandability, adipocyte hypertrophy, altered lipid metabolism, and local inflammation Recent human studies suggest that adipose tissue oxygenation may be a key factor herein A subgroup of obese individuals - the 'metabolically healthy obese' (MHO) - have a better adipose tissue function, less ectopic fat storage, and are more insulin sensitive than obese metabolically unhealthy persons, emphasizing the central role of adipose tissue function in metabolic health However, controversy has surrounded the idea that metabolically healthy obesity may be considered really healthy since MHO individuals are at increased (cardio)metabolic disease risk and may have a lower quality of life than normal weight subjects due to other comorbidities Detailed metabolic phenotyping of obese persons will be invaluable in understanding the pathophysiology of metabolic disturbances, and is needed to identify high-risk individuals or subgroups, thereby paving the way for optimization of prevention and treatment strategies to combat cardiometabolic diseases
1,822 citations
TL;DR: Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.
Abstract: There are currently over 1.9 billion people who are obese or overweight, leading to a rise in related health complications, including insulin resistance, type 2 diabetes, cardiovascular disease, liver disease, cancer, and neurodegeneration. The finding that obesity and metabolic disorder are accompanied by chronic low-grade inflammation has fundamentally changed our view of the underlying causes and progression of obesity and metabolic syndrome. We now know that an inflammatory program is activated early in adipose expansion and during chronic obesity, permanently skewing the immune system to a proinflammatory phenotype, and we are beginning to delineate the reciprocal influence of obesity and inflammation. Reviews in this series examine the activation of the innate and adaptive immune system in obesity; inflammation within diabetic islets, brain, liver, gut, and muscle; the role of inflammation in fibrosis and angiogenesis; the factors that contribute to the initiation of inflammation; and therapeutic approaches to modulate inflammation in the context of obesity and metabolic syndrome.
1,179 citations
TL;DR: Managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.
Abstract: Obesity is the accumulation of abnormal or excessive fat that may interfere with the maintenance of an optimal state of health. The excess of macronutrients in the adipose tissues stimulates them to release inflammatory mediators such as tumor necrosis factor α and interleukin 6, and reduces production of adiponectin, predisposing to a pro-inflammatory state and oxidative stress. The increased level of interleukin 6 stimulates the liver to synthesize and secrete C-reactive protein. As a risk factor, inflammation is an imbedded mechanism of developed cardiovascular diseases including coagulation, atherosclerosis, metabolic syndrome, insulin resistance, and diabetes mellitus. It is also associated with development of non-cardiovascular diseases such as psoriasis, depression, cancer, and renal diseases. On the other hand, a reduced level of adiponectin, a significant predictor of cardiovascular mortality, is associated with impaired fasting glucose, leading to type-2 diabetes development, metabolic abnormalities, coronary artery calcification, and stroke. Finally, managing obesity can help reduce the risks of cardiovascular diseases and poor outcome via inhibiting inflammatory mechanisms.
997 citations
TL;DR: In this mini review, the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM are outlined.
Abstract: Type 2 diabetes mellitus (T2DM) is a global pandemic, as evident from the global cartographic picture of diabetes by the International Diabetes Federation (http://www.diabetesatlas.org/). Diabetes mellitus is a chronic, progressive, incompletely understood metabolic condition chiefly characterized by hyperglycemia. Impaired insulin secretion, resistance to tissue actions of insulin, or a combination of both are thought to be the commonest reasons contributing to the pathophysiology of T2DM, a spectrum of disease originally arising from tissue insulin resistance and gradually progressing to a state characterized by complete loss of secretory activity of the beta cells of the pancreas. T2DM is a major contributor to the very large rise in the rate of non-communicable diseases affecting developed as well as developing nations. In this mini review, we endeavor to outline the current management principles, including the spectrum of medications that are currently used for pharmacologic management, for lowering the elevated blood glucose in T2DM.
841 citations
TL;DR: This Perspective reviews alternate viewpoints and recent results on the temporal and mechanistic connections between hyperinsulinemia, obesity and insulin resistance and connects insulin resistance to extensive metabolic cross-talk between the liver, adipose tissue, pancreas and skeletal muscle.
Abstract: Nutritional excess is a major forerunner of type 2 diabetes. It enhances the secretion of insulin, but attenuates insulin's metabolic actions in the liver, skeletal muscle and adipose tissue. However, conflicting evidence indicates a lack of knowledge of the timing of these events during the development of obesity and diabetes, pointing to a key gap in our understanding of metabolic disease. This Perspective reviews alternate viewpoints and recent results on the temporal and mechanistic connections between hyperinsulinemia, obesity and insulin resistance. Although much attention has addressed early steps in the insulin signaling cascade, insulin resistance in obesity seems to be largely elicited downstream of these steps. New findings also connect insulin resistance to extensive metabolic cross-talk between the liver, adipose tissue, pancreas and skeletal muscle. These and other advances over the past 5 years offer exciting opportunities and daunting challenges for the development of new therapeutic strategies for the treatment of type 2 diabetes.
784 citations
TL;DR: Diabetes and hypertension as comorbidities are discussed and some vascular mechanisms that predispose to both conditions are highlighted, focusing on advanced glycation end products, oxidative stress, inflammation, the immune system, and microRNAs.
771 citations
TL;DR: Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight, thus suggesting potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis.
Abstract: Adiponectin is the most abundant peptide secreted by adipocytes, whose reduction plays a central role in obesity-related diseases, including insulin resistance/type 2 diabetes and cardiovascular disease. In addition to adipocytes, other cell types, such as skeletal and cardiac myocytes and endothelial cells, can also produce this adipocytokine. Adiponectin effects are mediated by adiponectin receptors, which occur as two isoforms (AdipoR1 and AdipoR2). Adiponectin has direct actions in liver, skeletal muscle, and the vasculature.Adiponectin exists in the circulation as varying molecular weight forms, produced by multimerization. Several endoplasmic reticulum ER-associated proteins, including ER oxidoreductase 1-α (Ero1-α), ER resident protein 44 (ERp44), disulfide-bond A oxidoreductase-like protein (DsbA-L), and glucose-regulated protein 94 (GPR94), have recently been found to be involved in the assembly and secretion of higher-order adiponectin complexes. Recent data indicate that the high-molecular weight (HMW) complexes have the predominant action in metabolic tissues. Studies have shown that adiponectin administration in humans and rodents has insulin-sensitizing, anti-atherogenic, and anti-inflammatory effects, and, in certain settings, also decreases body weight. Therefore, adiponectin replacement therapy in humans may suggest potential versatile therapeutic targets in the treatment of obesity, insulin resistance/type 2 diabetes, and atherosclerosis. The current knowledge on regulation and function of adiponectin in obesity, insulin resistance, and cardiovascular disease is summarized in this review.
720 citations
TL;DR: These studies show that ATMs in obese mice secrete exosomes containing miRNA cargo, which can be transferred to insulin target cell types through mechanisms of paracrine or endocrine regulation with robust effects on cellular insulin action, in vivo insulin sensitivity, and overall glucose homeostasis.
712 citations
TL;DR: Increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction in obese women.
Abstract: Obesity is the most common medical condition in women of reproductive age. Obesity during pregnancy has short term and long term adverse consequences for both mother and child. Obesity causes problems with infertility, and in early gestation it causes spontaneous pregnancy loss and congenital anomalies. Metabolically, obese women have increased insulin resistance in early pregnancy, which becomes manifest clinically in late gestation as glucose intolerance and fetal overgrowth. At term, the risk of cesarean delivery and wound complications is increased. Postpartum, obese women have an increased risk of venous thromboembolism, depression, and difficulty with breast feeding. Because 50-60% of overweight or obese women gain more than recommended by Institute of Medicine gestational weight guidelines, postpartum weight retention increases future cardiometabolic risks and prepregnancy obesity in subsequent pregnancies. Neonates of obese women have increased body fat at birth, which increases the risk of childhood obesity. Although there is no unifying mechanism responsible for the adverse perinatal outcomes associated with maternal obesity, on the basis of the available data, increased prepregnancy maternal insulin resistance and accompanying hyperinsulinemia, inflammation, and oxidative stress seem to contribute to early placental and fetal dysfunction. We will review the pathophysiology underlying these data and try to shed light on the specific underlying mechanisms.
669 citations
TL;DR: Obesity is associated with a large decrease in life expectancy, but up to 30% of obese patients are metabolically healthy with insulin sensitivity similar to healthy normal weight individuals, lower visceral fat content, and lower intima media thickness of the carotid artery than the majority of metabolically "unhealthy" obese patients.
Abstract: Increase in prevalence of obesity has become a worldwide major health problem in adults, as well as among children and adolescents. Furthermore, total adiposity and truncal subcutaneous fat accumulation during adolescence are positively and independently associated with atherosclerosis at adult ages. Centrally accumulation of body fat is associated with insulin resistance, whereas distribution of body fat in a peripheral pattern is metabolically less important. Obesity is associated with a large decrease in life expectancy. The effect of extreme obesity on mortality is greater among younger than older adults. In this respect, obesity is also associated with increased risk of several cancer types. However, up to 30% of obese patients are metabolically healthy with insulin sensitivity similar to healthy normal weight individuals, lower visceral fat content, and lower intima media thickness of the carotid artery than the majority of metabolically “unhealthy” obese patients.
TL;DR: The term periodic fasting (PF) is used to describe eating patterns in which individuals go extended time periods (e.g., 16-48h) with little or no energy intake, with intervening periods of normal food intake, on a recurring basis as mentioned in this paper.
TL;DR: The multifaceted and complex interactions between the liver and T2DM are described, which show some efficacy in the treatment of NASH.
Abstract: The association between NAFLD and diabetes mellitus has garnered increasing attention in the past few years. In this Review, Tilg and colleagues explore in detail the molecular mechanisms linking NAFLD and diabetes mellitus, and discuss clinical aspects arising from the interaction of both diseases. The liver constitutes a key organ in systemic metabolism, contributing substantially to the development of insulin resistance and type 2 diabetes mellitus (T2DM). The mechanisms underlying these processes are not entirely understood, but involve hepatic fat accumulation, alterations of energy metabolism and inflammatory signals derived from various cell types including immune cells. Lipotoxins, mitochondrial function, cytokines and adipocytokines have been proposed to play a major part in both NAFLD and T2DM. Patients with NAFLD are commonly insulin resistant. On the other hand, a large number of patients with T2DM develop NAFLD with its inflammatory complication, NASH. The high incidence of NASH in patients with T2DM leads to further complications, such as liver cirrhosis and hepatocellular carcinoma, which are increasingly recognized. Therapeutic concepts such as thiazolidinediones (glitazones) for treating T2DM also show some efficacy in the treatment of NASH. This Review will describe the multifaceted and complex interactions between the liver and T2DM.
TL;DR: A mechanism for the progression of subclinical hepatic insulin resistance to overt fasting hyperglycaemia in type 2 diabetes mellitus is proposed and the therapeutic potential of strategies that target hepatosteatosis, hyperglucagonaemia and adipose lipolysis is considered.
Abstract: The liver is crucial for the maintenance of normal glucose homeostasis - it produces glucose during fasting and stores glucose postprandially. However, these hepatic processes are dysregulated in type 1 and type 2 diabetes mellitus, and this imbalance contributes to hyperglycaemia in the fasted and postprandial states. Net hepatic glucose production is the summation of glucose fluxes from gluconeogenesis, glycogenolysis, glycogen synthesis, glycolysis and other pathways. In this Review, we discuss the in vivo regulation of these hepatic glucose fluxes. In particular, we highlight the importance of indirect (extrahepatic) control of hepatic gluconeogenesis and direct (hepatic) control of hepatic glycogen metabolism. We also propose a mechanism for the progression of subclinical hepatic insulin resistance to overt fasting hyperglycaemia in type 2 diabetes mellitus. Insights into the control of hepatic gluconeogenesis by metformin and insulin and into the role of lipid-induced hepatic insulin resistance in modifying gluconeogenic and net hepatic glycogen synthetic flux are also discussed. Finally, we consider the therapeutic potential of strategies that target hepatosteatosis, hyperglucagonaemia and adipose lipolysis.
TL;DR: The beneficial effects of lean donor FMT on glucose metabolism are associated with changes in intestinal microbiota and plasma metabolites and can be predicted based on baseline fecal microbiota composition.
TL;DR: Advances in "omics" technologies have further stimulated additional basic and clinical-translational research to further interrogate mechanisms for improved metabolic flexibility in skeletal muscle and adipose tissue with the goal of preventing and treating metabolic disease.
TL;DR: Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications.
Abstract: Metformin (dimethylbiguanide) has become the preferred first-line oral blood glucose-lowering agent to manage type 2 diabetes. Its history is linked to Galega officinalis (also known as goat's rue), a traditional herbal medicine in Europe, found to be rich in guanidine, which, in 1918, was shown to lower blood glucose. Guanidine derivatives, including metformin, were synthesised and some (not metformin) were used to treat diabetes in the 1920s and 1930s but were discontinued due to toxicity and the increased availability of insulin. Metformin was rediscovered in the search for antimalarial agents in the 1940s and, during clinical tests, proved useful to treat influenza when it sometimes lowered blood glucose. This property was pursued by the French physician Jean Sterne, who first reported the use of metformin to treat diabetes in 1957. However, metformin received limited attention as it was less potent than other glucose-lowering biguanides (phenformin and buformin), which were generally discontinued in the late 1970s due to high risk of lactic acidosis. Metformin's future was precarious, its reputation tarnished by association with other biguanides despite evident differences. The ability of metformin to counter insulin resistance and address adult-onset hyperglycaemia without weight gain or increased risk of hypoglycaemia gradually gathered credence in Europe, and after intensive scrutiny metformin was introduced into the USA in 1995. Long-term cardiovascular benefits of metformin were identified by the UK Prospective Diabetes Study (UKPDS) in 1998, providing a new rationale to adopt metformin as initial therapy to manage hyperglycaemia in type 2 diabetes. Sixty years after its introduction in diabetes treatment, metformin has become the most prescribed glucose-lowering medicine worldwide with the potential for further therapeutic applications.
TL;DR: Clinical significant hypoglycemia is now defined at blood glucose levels <54 mg/dL, whereas blood sugar levels <70mg/dL should be used as an “alert value” to help individuals avoid more severe hypoglycesmia.
Abstract: The American Diabetes Association’s (ADA) 2017 Standards of Care were published in Diabetes Care on 15 December 2016. Notable changes in the new guidelines include the recommendation of sodiumglucose cotransporter 2 (SGLT-2) inhibitor empagliflozin and glucagon-like peptide 1 (GLP-1) agonist liraglutide for type 2 diabetes (T2D) patients at high risk for cardiovascular morbidity and mortality. Data from the Empagliflozin, Cardiovascular Outcomes, and Mortality in Type 2 Diabetes (EMPA-REG OUTCOME) trial and the Liraglutide Effect and Action in Diabetes: Evaluation of Cardiovascular Outcome Results (LEADER) trial are now included in the section on cardiovascular disease and risk management. In addition, fixed-ratio combinations of a basal insulin and a GLP-1 agonist are included in the algorithm for combination therapy, just weeks after the first of these products, Novo Nordisk’s (Copenhagen, Denmark) Xultophy (insulin degludec/liraglutide) and Sanofi’s (Paris, France) Soliqua (insulin glargine/lixisenatide), were approved by the US Food and Drug Administration (FDA) for prescription in the US. Based on recommendations from the International Hypoglycemia Study Group, the ADA’s 2017 Standards of Care features a new classification for hypoglycemia: clinically significant hypoglycemia is now defined at blood glucose levels <54 mg/dL, whereas blood glucose levels <70 mg/dL should be used as an “alert value” to help individuals avoid more severe hypoglycemia. The ADA’s new guidelines also include a greater emphasis on cost of diabetes drugs, T2D prevention (with a push for more frequent prediabetes screenings), and psychosocial support in diabetes care, especially for adolescents and pediatric patients.
TL;DR: Molecular mechanisms that link obesity, diabetes and AD, including oxidative stress, mitochondrial dysfunction, and inflammation that are observed in these disorders are discussed.
TL;DR: The findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.
Abstract: Insulin resistance is a key mediator of obesity-related cardiometabolic disease, yet the mechanisms underlying this link remain obscure. Using an integrative genomic approach, we identify 53 genomic regions associated with insulin resistance phenotypes (higher fasting insulin levels adjusted for BMI, lower HDL cholesterol levels and higher triglyceride levels) and provide evidence that their link with higher cardiometabolic risk is underpinned by an association with lower adipose mass in peripheral compartments. Using these 53 loci, we show a polygenic contribution to familial partial lipodystrophy type 1, a severe form of insulin resistance, and highlight shared molecular mechanisms in common/mild and rare/severe insulin resistance. Population-level genetic analyses combined with experiments in cellular models implicate CCDC92, DNAH10 and L3MBTL3 as previously unrecognized molecules influencing adipocyte differentiation. Our findings support the notion that limited storage capacity of peripheral adipose tissue is an important etiological component in insulin-resistant cardiometabolic disease and highlight genes and mechanisms underpinning this link.
TL;DR: The metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated are evaluated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation is evaluated.
Abstract: The AMP-activated protein kinase (AMPK) is a central regulator of multiple metabolic pathways and may have therapeutic importance for treating obesity, insulin resistance, type 2 diabetes (T2D), non-alcoholic fatty liver disease (NAFLD), and cardiovascular disease (CVD). Given the ubiquitous expression of AMPK, it has been a challenge to evaluate which tissue types may be most beneficially poised for mediating the positive metabolic effects of AMPK-centered treatments. In this review we evaluate the metabolic phenotypes of transgenic mouse models in which AMPK expression and function have been manipulated, and the impact this has on controlling lipid metabolism, glucose homeostasis, and inflammation. This information may be useful for guiding the development of AMPK-targeted therapeutics to treat chronic metabolic diseases.
TL;DR: Evidence is provided that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle, and recent advances in the understanding of how Steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication are discussed.
Abstract: Hepatic steatosis is an underlying feature of nonalcoholic fatty liver disease (NAFLD), which is the most common form of liver disease and is present in up to ∼70% of individuals who are overweight. NAFLD is also associated with hypertriglyceridaemia and low levels of HDL, glucose intolerance, insulin resistance and type 2 diabetes mellitus. Hepatic steatosis is a strong predictor of the development of insulin resistance and often precedes the onset of other known mediators of insulin resistance. This sequence of events suggests that hepatic steatosis has a causal role in the development of insulin resistance in other tissues, such as skeletal muscle. Hepatokines are proteins that are secreted by hepatocytes, and many hepatokines have been linked to the induction of metabolic dysfunction, including fetuin A, fetuin B, retinol-binding protein 4 (RBP4) and selenoprotein P. In this Review, we describe the factors that influence the development of hepatic steatosis, provide evidence of strong links between hepatic steatosis and insulin resistance in non-hepatic tissues, and discuss recent advances in our understanding of how steatosis alters hepatokine secretion to influence metabolic phenotypes through inter-organ communication.
TL;DR: It is shown 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.
TL;DR: This Review presents the current knowledge on the physiology of irisin and its role in glucose homeostasis, and describes the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement.
Abstract: Irisin is a myokine that leads to increased energy expenditure by stimulating the 'browning' of white adipose tissue. In the first description of this hormone, increased levels of circulating irisin, which is cleaved from its precursor fibronectin type III domain-containing protein 5, were associated with improved glucose homeostasis by reducing insulin resistance. Consequently, several studies attempted to characterize the role of irisin in glucose regulation, but contradictory results have been reported, and even the existence of this hormone has been questioned. In this Review, we present the current knowledge on the physiology of irisin and its role in glucose homeostasis. We describe the mechanisms involved in the synthesis, secretion, circulation and regulation of irisin, and the controversies regarding the measurement of irisin. We also discuss the direct effects of irisin on glucose regulatory mechanisms in different organs, the indirect effects and interactions with other hormones, and the important open questions with regard to irisin in those organs. Finally, we present the results from animal interventional studies and from human clinical studies investigating the association of irisin with obesity, insulin resistance, type 2 diabetes mellitus and the metabolic syndrome.
TL;DR: Significant shared mechanisms between AD and diabetes are discussed and therapeutic avenues for diabetes and AD are provided and the effects of insulin in the pathology of AD through cellular and molecular mechanisms are provided.
TL;DR: Evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue.
Abstract: Obesity is associated with chronic inflammation, which contributes to insulin resistance and type 2 diabetes mellitus. Under normal conditions, skeletal muscle is responsible for the majority of insulin-stimulated whole-body glucose disposal; thus, dysregulation of skeletal muscle metabolism can strongly influence whole-body glucose homeostasis and insulin sensitivity. Increasing evidence suggests that inflammation occurs in skeletal muscle in obesity and is mainly manifested by increased immune cell infiltration and proinflammatory activation in intermyocellular and perimuscular adipose tissue. By secreting proinflammatory molecules, immune cells may induce myocyte inflammation, adversely regulate myocyte metabolism, and contribute to insulin resistance via paracrine effects. Increased influx of fatty acids and inflammatory molecules from other tissues, particularly visceral adipose tissue, can also induce muscle inflammation and negatively regulate myocyte metabolism, leading to insulin resistance.
TL;DR: It is suggested that higher PM may induce metabolic alterations that are consistent with activations of the hypothalamus-pituitary-adrenal and sympathetic- adrenal-medullary axes, adding potential mechanistic insights into the adverse health outcomes associated with PM.
Abstract: Background Exposure to ambient particulate matter (PM) is associated with a number of adverse health outcomes, but potential mechanisms are largely unknown. Metabolomics represents a powerful approach to study global metabolic changes in response to environmental exposures. We therefore conducted this study to investigate changes in serum metabolites in response to the reduction of PM exposure among healthy college students. Methods We conducted a randomized, double-blind crossover trial in 55 healthy college students in Shanghai, China. Real and sham air purifiers were placed in participants' dormitories in random order for 9 days with a 12-day washout period. Serum metabolites were quantified by using gas chromatography-mass spectrometry and ultrahigh performance liquid chromatography-mass spectrometry. Between-treatment differences in metabolites were examined using orthogonal partial least square-discriminant analysis and mixed-effect models. Secondary outcomes include blood pressure, corticotropin-releasing hormone, adrenocorticotropic hormone, insulin resistance, and biomarkers of oxidative stress and inflammation. Results The average personal exposure to PMs with aerodynamic diameters ≤2.5 μm was 24.3 μg/m3 during the real purification and 53.1 μg/m3 during the sham purification. Metabolomics analysis showed that higher exposure to PMs with aerodynamic diameters ≤2.5 μm led to significant increases in cortisol, cortisone, epinephrine, and norepinephrine. Between-treatment differences were also observed for glucose, amino acids, fatty acids, and lipids. We found significantly higher blood pressure, hormones, insulin resistance, and biomarkers of oxidative stress and inflammation among individuals exposed to higher PMs with aerodynamic diameters ≤2.5 μm. Conclusions This study suggests that higher PM may induce metabolic alterations that are consistent with activations of the hypothalamus-pituitary-adrenal and sympathetic-adrenal-medullary axes, adding potential mechanistic insights into the adverse health outcomes associated with PM. Furthermore, our study demonstrated short-term reductions in stress hormone following indoor air purification. Clinical trial registration URL: http://www.clinicaltrials.gov. Unique identifier: NCT02712333.
TL;DR: A review of sources of short chain fatty acids, with emphasis on sources ofbutyrate, mechanisms of fiber and butyrate metabolism in the gut and its protective effects on colon cancer and the peripheral effects of butyrates supplementation in peripheral tissues in the prevention and reversal of obesity and insulin resistance.
Abstract: Increased dietary fiber consumption has been associated with many beneficial effects, including amelioration of obesity and insulin resistance. These effects may be due to the increased production of short chain fatty acids, including propionate, acetate and butyrate, during fermentation of the dietary fiber in the colon. Indeed, oral and dietary supplementation of butyrate alone has been shown to prevent high fat-diet induced obesity and insulin resistance. This review focuses on sources of short chain fatty acids, with emphasis on sources of butyrate, mechanisms of fiber and butyrate metabolism in the gut and its protective effects on colon cancer and the peripheral effects of butyrate supplementation in peripheral tissues in the prevention and reversal of obesity and insulin resistance.
TL;DR: The molecular mechanisms involved in the pathogenesis of NAFLD, including macrophage/Kupffer cell polarization, and disturbed hepatic function inNAFLD are summarized and dietary antioxidants, such as β-cryptoxanthin and astaxanthin, that may be effective in the prevention or treatment of NA FLD are discussed.
Abstract: Nonalcoholic fatty liver disease (NAFLD) is one of the most common chronic liver disorders worldwide. It is associated with clinical states such as obesity, insulin resistance, and type 2 diabetes, and covers a wide range of liver changes, ranging from simple steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Metabolic disorders, such as lipid accumulation, insulin resistance, and inflammation, have been implicated in the pathogenesis of NAFLD, but the underlying mechanisms, including those that drive disease progression, are not fully understood. Both innate and recruited immune cells mediate the development of insulin resistance and NASH. Therefore, modifying the polarization of resident and recruited macrophage/Kupffer cells is expected to lead to new therapeutic strategies in NAFLD. Oxidative stress is also pivotal for the progression of NASH, which has generated interest in carotenoids as potent micronutrient antioxidants in the treatment of NAFLD. In addition to their antioxidative function, carotenoids regulate macrophage/Kupffer cell polarization and thereby prevent NASH progression. In this review, we summarize the molecular mechanisms involved in the pathogenesis of NAFLD, including macrophage/Kupffer cell polarization, and disturbed hepatic function in NAFLD. We also discuss dietary antioxidants, such as β-cryptoxanthin and astaxanthin, that may be effective in the prevention or treatment of NAFLD.
TL;DR: Prevalence of metabolic syndrome in children and adolescents is increasing, in parallel with the increasing trends in obesity rates, and variations in definitions of this syndrome have hindered the development of a consensus for the diagnostic criteria in the pediatric population.
Abstract: Prevalence of metabolic syndrome in children and adolescents is increasing, in parallel with the increasing trends in obesity rates. Varying definitions of this syndrome have hindered the development of a consensus for the diagnostic criteria in the pediatric population. While pathogenesis of metabolic syndrome is not completely understood, insulin resistance and subsequent inflammation are thought to be among its main mechanistic underpinnings. Overweight and obesity are cardinal features, along with abnormal glucose metabolism, dyslipidemia, and hypertension. Other disorders associated with metabolic syndrome include fatty liver, polycystic ovarian syndrome (PCOS), and pro-inflammatory states. Prevention and management of this condition can be accomplished with lifestyle modifications, behavioral interventions, pharmacological and surgical interventions as needed.