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Query: UMLS:C0948265 (metabolic syndrome)
 24,271 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Maternal obesity is a risk factor for the development of metabolic syndrome and childhood obesity, and early overnutrition seems to induce the development of pathologies in adulthood, including insulin resistance, cardiovascular diseases, type 2 diabetes mellitus, and a higher BMI. In addition, it is known that obesity can negatively affect fertility and reproductive function in men. The objective of this work was to investigate the impact of maternal obesity induced by the consumption of cafeteria diet on metabolic, endocrine and reproductive outcomes in the male offspring. Body weight, abdominal fat content and concentrations of insulin, leptin, glucose and total cholesterol were analyzed in dams. The same parameters were evaluated in pups when in adulthood, in addition to the analysis of sexual behavior, followed by measurement of plasma luteinizing hormone, follicle-stimulating hormone, testosterone, and prolactin. Maternal consumption of cafeteria diet affected reproductive hormone regulation in the offspring and such modifications were reflected on sexual performance. Also, these modifications were independent of time and of the reproductive period during which dams consumed the diet. Our results indicate, for the first time, that maternal nutrition may have a deep impact on the reproductive function of the adult male offspring.
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PMID:The impact of maternal consumption of cafeteria diet on reproductive function in the offspring. 2463 2

The importance of diet in health and disease has been well characterized in the past decades. Although the earlier focus of diet research was in the context of undernutrition and the importance of adequate nutrient intake to prevent malnutrition, in the current era of epidemic obesity the focus of our efforts has evolved toward understanding the effects of excess caloric intake. The current surge in childhood obesity rates suggests a correlation of maternal metabolic syndrome and obesity with programming of the fetal epigenome for metabolic diseases later in life. Alterations of the fetal genome, epigenome and metabolome have been well documented in cases of maternal malnutrition, including both overnutrition and undernutrition. It is of great interest and importance to understand how these divergent maternal factors regulate/program the fetus for metabolic diseases, and we and others have observed that epigenetic modifications to the fetal and placental epigenome accompany these reprogramming events. The following review summarizes recent studies on the effects of maternal diet and obesity on fetal epigenetics contributing to adult diseases later in life by taking advantage of state-of-the-art genomic, epigenomic and metagenomic techniques in nonhuman primate model systems.
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PMID:Maternal diet: a modulator for epigenomic regulation during development in nonhuman primates and humans. 2501 72

Chronic overnutrition creates chronic hyperglycemia that can gradually induce insulin resistance and insulin secretion impairment. These disorders, if not intervened, will eventually be followed by appearance of frank diabetes. The mechanisms of this chronic pathogenic process are complex but have been suggested to involve production of reactive oxygen species (ROS) and oxidative stress. In this review, I highlight evidence that reductive stress imposed by overflux of NADH through the mitochondrial electron transport chain is the source of oxidative stress, which is based on establishments that more NADH recycling by mitochondrial complex I leads to more electron leakage and thus more ROS production. The elevated levels of both NADH and ROS can inhibit and inactivate glyceraldehyde 3-phosphate dehydrogenase (GAPDH), respectively, resulting in blockage of the glycolytic pathway and accumulation of glycerol 3-phospate and its prior metabolites along the pathway. This accumulation then initiates all those alternative glucose metabolic pathways such as the polyol pathway and the advanced glycation pathways that otherwise are minor and insignificant under euglycemic conditions. Importantly, all these alternative pathways lead to ROS production, thus aggravating cellular oxidative stress. Therefore, reductive stress followed by oxidative stress comprises a major mechanism of hyperglycemia-induced metabolic syndrome.
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PMID:Pathogenesis of chronic hyperglycemia: from reductive stress to oxidative stress. 2501 91

Maternal malnutrition during pregnancy, both deficiency and excess, induces changes in the intrauterine environment and the metabolic status of the offspring, playing a key role in the growth, status of fitness/obesity and appearance of metabolic disorders during postnatal life. There is increasing evidence that these effects may not be only limited to the first generation of descendants, the offspring directly exposed to metabolic challenges, but to subsequent generations. This study evaluated, in a swine model of obesity/leptin resistance, the existence and extent of transgenerational developmental programming effects. Pre- and postnatal development, adiposity and metabolic features were assessed in the second generation of piglets, descendant of sows exposed to either undernutrition or overnutrition during pregnancy. The results indicated that these piglets exhibited early-postnatal increases in adiposity and disturbances in lipid profiles compatible with the early prodrome of metabolic syndrome, with liver tissue also displaying evidence of paediatric liver disease. These features indicative of early-life metabolic disorders were more evident in the males that were descended from overfed grandmothers and during the transition from milk to solid feeding. Thus, this study provides evidence supporting transgenerational developmental programming and supports the necessity for the development of strategies for avoiding the current epidemics of childhood overweight and obesity.
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PMID:Early-postnatal changes in adiposity and lipids profile by transgenerational developmental programming in swine with obesity/leptin resistance. 2510 35

Exposure to overnutrition in critical or sensitive developmental periods may increase the risk of developing obesity and metabolic syndrome in adults. Nonalcoholic fatty liver disease (NAFLD) is the hepatic manifestation of the metabolic syndrome, but the relationship among postnatal nutrition, lipid metabolism, and NAFLD progression during development remains poorly understood. Here we investigated in a rat model whether postnatal overfeeding increases susceptibility to NAFLD in response to a high-fat diet. Litters from Sprague-Dawley dams were culled to three (small litters) or ten (normal litters) pups and then weaned onto a standard or high-fat diet at postnatal day 21 to generate normal-litter, small-litter, normal-litter/high-fat, and small-litter/high-fat groups. At age 16 weeks, the small-litter and both high-fat groups showed obesity, dyslipidemia, and insulin resistance. Hepatic disorders appeared earlier in the small-litter/high-fat rats with greater liver mass gain and higher hepatic triglycerides and steatosis score versus normal-litter/high-fat rats. Hepatic acetyl-CoA carboxylase activity and mRNA expression were increased in small-litter rats and aggravated in small-litter/high-fat rats but not in normal-litter/high-fat rats. The high expression in small-litter/high-fat rats coincided with high sterol regulatory element-binding protein-1c mRNA and protein expression. However, mRNA expression of enzymes involved in hepatic fatty acid oxidation (carnitine palmitoyltransferase 1) and output (microsomal triglyceride transfer protein) was decreased under a high-fat diet regardless of litter size. In conclusion, overfeeding related to small-litter rearing during lactation contributes to the NAFLD phenotype when combined with a high-fat diet, possibly through up-regulated hepatic lipogenesis.
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PMID:Postnatal overfeeding promotes early onset and exaggeration of high-fat diet-induced nonalcoholic fatty liver disease through disordered hepatic lipid metabolism in rats. 2515 69

Obesity- and metabolic syndrome-related diseases are becoming important medical challenges for the western world. Non-alcoholic fatty liver disease (NAFLD) is a manifestation of these altered conditions in the liver, and inflammation appears to be a factor that is tightly connected to its evolution. In this study, we used a diet-induced obesity approach in zebrafish (Danio rerio) based on overfeeding to analyze liver transcriptomic modulation in the disease and to determine how obesity affects the immune response against an acute inflammatory stimulus such as lipopolysaccharide (LPS). Overfed zebrafish developed an obese phenotype, showed signs of liver steatosis, and its modulation profile resembled that observed in humans, with overexpression of tac4, col4a3, col4a5, lysyl oxidases, and genes involved in retinoid metabolism. In response to LPS, healthy fish exhibited a typical host defense reaction comparable to that which occurs in mammals, whereas there was no significant gene modulation when comparing expression in the liver of LPS-stimulated and non-stimulated obese zebrafish at the same statistical level. The stimulation of obese fish represents a double-hit to the already damaged liver and can help understand the evolution of the disease. Finally, a comparison of the differential gene activation between stimulated healthy and obese zebrafish revealed the expected difference in the metabolic state between healthy and diseased liver. The differentially modulated genes are currently being studied as putative new pathological markers in NAFLD-stimulated liver in humans.
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PMID:Liver immune responses to inflammatory stimuli in a diet-induced obesity model of zebrafish. 2537 40

Chronic microinflammation is a hallmark of many aging-related neurodegenerative diseases as well as metabolic syndrome-driven diseases. Recent research indicates that chronic caloric excess can lead to hypothalamic microinflammation, which in turn participates in the development and progression of metabolic syndrome disorders such as obesity, glucose intolerance, and hypertension. Additionally, it was recently shown that increasing age after young adulthood can cause hypothalamic microinflammation independently of nutritional status, mediating a central mechanism of systemic aging. Taken together, these findings suggest that the hypothalamus has a fundamental role, via hypothalamic microinflammation, in translating overnutrition and aging into complex outcomes. Here we summarize recent work and suggest a conceptual model in which hypothalamic microinflammation is a common mediator of metabolic syndrome and aging.
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PMID:Hypothalamic microinflammation: a common basis of metabolic syndrome and aging. 2545 20

Metabolic syndrome is a cluster of risk factors including obesity, dyslipidemia, hypertension, and insulin resistance. A number of theories have been speculated for the pathogenesis of metabolic syndrome including impaired glucose and lipid metabolism, lipotoxicity, oxidative stress, interrupted neurohormonal regulation and compromised intracellular Ca(2+) handling. Recent evidence has revealed that adults with severe growth hormone (GH) and insulin-like growth factor I (IGF-1) deficiency such as Laron syndrome display increased risk of stroke and cardiovascular diseases. IGF-1 signaling may regulate contractility, metabolism, hypertrophy, apoptosis, autophagy, stem cell regeneration and senescence in the heart to maintain cardiac homeostasis. An inverse relationship between plasma IGF-1 levels and prevalence of metabolic syndrome as well as associated cardiovascular complications has been identified, suggesting the clinical promises of IGF-1 analogues or IGF-1 receptor activation in the management of metabolic and cardiovascular diseases. However, the underlying pathophysiological mechanisms between IGF-1 and metabolic syndrome are still poorly understood. This mini-review will discuss the role of IGF-1 signaling cascade in the prevalence of metabolic syndrome in particular the susceptibility to overnutrition and sedentary life style-induced obesity, dyslipidemia, insulin resistance and other features of metabolic syndrome. Special attention will be dedicated in IGF-1-associated changes in cardiac responses in various metabolic syndrome components such as insulin resistance, obesity, hypertension and dyslipidemia. The potential risk of IGF-1 and IGF-1R stimulation such as tumorigenesis is discussed. Therapeutic promises of IGF-1 and IGF-1 analogues including mecasermin, mecasermin rinfabate and PEGylated IGF-1 will be discussed.
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PMID:The insulin-like growth factor I system: physiological and pathophysiological implication in cardiovascular diseases associated with metabolic syndrome. 2554 Dec 85

The recent and rapid worldwide increase in non-communicable diseases challenges the assumption that genetic factors are the primary contributors to such diseases. A new concept of the 'developmental origins of health and disease' (DOHaD) is at stake and therefore requires a paradigm shift. Maternal obesity and malnutrition predispose offspring to develop metabolic syndrome, a vicious cycle leading to transmission to subsequent generation(s), with differences in response and susceptibility according to the sex of the individual. The placenta is a programming agent of adult health and disease. Adaptations of placental phenotype in response to maternal diet and metabolic status alter fetal nutrient supply. This implies important epigenetic changes that are, however, still poorly documented in DOHaD studies, particularly concerning overnutrition. The aim of this review is to discuss the emerging knowledge on the relationships between the effect of maternal nutrition or metabolic status on placental function and the risk of diseases later in life, with a specific focus on epigenetic mechanisms and sexual dimorphism. Explaining the sex-specific causal variables and how males versus females respond and adapt to environmental perturbations should help physicians and patients to anticipate disease susceptibility.
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PMID:Placental contribution to nutritional programming of health and diseases: epigenetics and sexual dimorphism. 2556 51

The metabolic syndrome represents a cluster of closely connected premorbid risk factors or diseases with visceral obesity type 2 diabetes, hypertension and low HLD/hypertriglyceridemia as established traits affecting about 20% in the adult European populations. This syndrome develops on a complex soil with overnutrition, low physical activity and psychosocial stress. Common comorbidities are fatty liver, sleep apnoe and endothelial dysfunction with cardiovascular complications, nephropathy and type 2 diabetes as "end-stage" diseases. Thus, a rational diagnostic is needed to elucidate the complex cluster of diseases as basis for an integrated therapy. There is a clear priority for life style intervention, however, most diseases of the metabolic syndrome need medical treatment. Medical treatment of single traits has to take into account possible pleiotropic or adverse effects on the other traits. This paper presents the pros and cons of major drug intervention for type 2 diabetes, hypertension, dyslipidemia and hypercoagulation in the context with the metabolic syndrome.
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PMID:The metabolic syndrome and cardiovascular disease - an ongoing tsunami. 2561 64


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