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

To determine whether adipocyte storage capacity influences the onset and severity of type 2 diabetes and other components of the metabolic syndrome, we made normal and db/db mice resistant to obesity by overexpressing leptin receptor-b on the aP2-Lepr-b promoter. On a 4% diet, these mice have no phenotype, but on a 60% fat diet, they resist diet-induced obesity because constitutive adipocyte-specific overexpression of Lepr-b prevents obesity via the antilipogenic autocrine/paracrine action of leptin on adipocytes. After 8 months on the same 60% fat diet, body fat of transgenic mice was 70% below WT controls. Cardiac and liver fat was elevated in the transgenics, and their hyperinsulinemia was more marked, suggesting greater insulin resistance. The aP2-Lepr-b transgene also prevented obesity in db/db mice; at 10 weeks of age their body fat was half that of the db/db mice. This lack of obesity was attributable to reduced expression of sterol regulatory element binding protein-1c and its target lipogenic enzymes in adipose tissue and a 6-fold increase in Pref-1 mRNA. Severe diabetes was present in transgenics at 4 weeks of age, 10 weeks before db/db controls. Echocardiographic evidence of cardiomyopathy appeared at 10 weeks, weeks before the db/db mice. Histologically, loss of beta cells and myocardial fibrosis was present in the transgenic group at least 6 weeks before the db/db mice. These results suggest that the expression level of genes that regulate the adipogenic response to overnutrition profoundly influences the age of onset and severity of diet-induced type 2 diabetes and co-morbidities.
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PMID:Adipogenic capacity and the susceptibility to type 2 diabetes and metabolic syndrome. 1841 98

Obesity is defined as increased body weight caused by excessive accumulation of fat. Due to a very long period of undernutrition in human history, the contemporary human body regulation mechanisms seem to be biased in favor of preserving fat rather to eliminate it. At the highest risk are populations that suddenly gained wealth. The shift from undernutrition to overnutrition has occurred in a very short time, in many population groups in less than in one generation. The increase of obesity prevalence observed in the 20th century continues until present and it appears this trend will further continue in almost all countries in the world. Contemporary prevalence of adult obesity is very high in USA (33% in both gender), in oil-rich Arabian countries (30% in males, 40 % in females) and in European Union (up to 25% in both gender). The aim of contemporary research is to understand the molecular and neural systems which the body uses to regulate its storage of energy in the form of fat and how these systems can become unbalanced, leading to obesity. In spite of discovery of new hormones (e.g. leptin produced in adipose tissue) and of new mechanisms, the prevention and treatment of obesity remains an open problem. Obesity is associated with an increased risk of numerous comorbidities such as type 2 diabetes, metabolic syndrome, hypertension, cardiovascular diseases and osteoarthritis. In USA the impact of obesity on mortality may have decreased over time, perhaps because of improvements in public health and medical care. New data from USA and China suggest the lowest all-cause mortality in persons with a body mass index, BMI between 23.0 and 27.0 (Fig. 6, Tab. 1, Ref. 29). Full Text (Free, PDF) www.bmj.sk.
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PMID:Adult obesity at the beginning of the 21st century: epidemiology, pathophysiology and health risk. 1863 Aug 7

Non-alcoholic fatty liver disease (NAFLD) covers a wide spectrum of liver pathology--from steatosis alone, through the necroinflammatory disorder of non-alcoholic steatohepatitis (NASH) to cirrhosis and liver cancer. NAFLD/NASH is mostly related with visceral adiposity, obesity, type 2 diabetes melitus (DM t.2) and metabolic syndrome. Pathogenetic concepts of NAFLD include overnutrition and underactivity, insulin resistance (IR) and genetic factor. The prevalence of NAFLD has been estimated to be 17-33% in some countries, NASH may be present in about 1/3 of such cases, while 20-25% of NASH cases could progress to cirrhosis. NAFLD is now recognized as one of the most frequent reason of liver tests elevation without clinical symptoms. Insulin resistance is considering as having a central role in NAFLD pathogenesis. In hepatocytes, IR is related to hyperglycaemia and hyperinsulinaemia, formation of advanced glycation end-products, increased free fatty acids and their metabolites, oxidative stress and altered profiles of adipocytokines. Early stages of fatty liver are clinically silent and include elevation of ALT and GGTP, hyperechogenic liver in USG and/or hepatomegaly. Among clinical symptoms, abdominal discomfort is relatively common as well as chronic fatigue. NAFLD/NASH is not a benign disease, progressive liver biopsy have shown histological progression of fibrosis in 32%, the estimated rate of cirrhosis development is 20% and a liver--related death is 12% over 10 years. No treatment has scientifically proved to ameliorate NAFLD or to avoid its progression. The various therapeutic alternatives are aimed at interfering with the risk factors involved in the pathogenesis of the disorder in order to prevent the progression to end-stage liver disease. The most important therapeutic measure is increasing insulin sensitivity by an attempt to change a lifestyle mostly by dieting and physical activity in order to loose weight. The most used agent is metformin, the others are under controlled trials or their effectiveness is low. NASH is not a common indication for liver transplantation because of the older age distribution of patients and high prevalence of comorbidity, related to metabolic syndrome. Recurence of NASH in the grafted liver is also a relatively frequent complication.
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PMID:[Non-alcoholic fatty liver disease--new view]. 1870 46

Non-alcoholic fatty liver disease (NAFLD) is the most common cause of referral to liver clinics, and its progressive form, non-alcoholic steatohepatitis (NASH), can lead to cirrhosis and end-stage liver disease. The main risk factors for NAFLD/NASH are the metabolic abnormalities commonly observed in metabolic syndrome: insulin resistance, visceral obesity, dyslipidemia and altered adipokine profile. At present, the causes of progression from NAFLD to NASH remain poorly defined, and research in this area has been limited by the availability of suitable animal models of this disease. In the past, the main models used to investigate the pathogenesis of steatohepatitis have either failed to reproduce the full spectrum of liver pathology that characterizes human NASH, or the liver pathology has developed in a metabolic context that is not representative of the human condition. In the last few years, a number of models have been described in which the full spectrum of liver pathology develops in an appropriate metabolic context. In general, the underlying cause of metabolic defects in these models is chronic caloric overconsumption, also known as overnutrition. Overnutrition has been achieved in a number of different ways, including forced feeding, administration of high-fat diets, the use of genetically hyperphagic animals, or a combination of these approaches. The purpose of the present review is to critique the liver pathology and metabolic abnormalities present in currently available animal models of NASH, with particular focus on models described in approximately the last 5 years.
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PMID:Animal models of NASH: getting both pathology and metabolic context right. 1875 64

Postnatal early overnutrition (EO) is a risk factor for obesity in adult life. Rats raised in a small litter can develop hyperinsulinaemia, hyperphagia, hyperleptinaemia and hypertension as adults. Since leptin regulates the hypothalamic-pituitary-thyroid axis and the metabolism of thyroid hormones, we studied the leptin signalling pathway in pituitary and thyroid glands of the postnatal EO model. To induce EO, at the third day of lactation the litter size was reduced to three pups per litter (SL group). In control litters (NL group), the litter size was adjusted to 10 pups per litter. Body weight and food intake were monitored. Rat offspring were killed at 21 (weaning) and 180 days old (adulthood). Plasma thyroid hormones, thyroid-stimulating hormone (TSH) and leptin were measured by radioimmunoassay. Proteins of the leptin signalling pathway were analysed by Western blotting. Body weight of offspring in the SL group was higher from the seventh day of lactation (+33%, P < 0.05) until 180 days old (+18%, P < 0.05). Offspring in the SL group showed higher visceral fat mass at 21 and 180 days old (+176 and +52%, respectively, P < 0.05), but plasma leptin was higher only at 21 days (+88%, P < 0.05). The SL offspring showed higher plasma TSH, 3,5,3'-triiodothronine (T(3)) and thyroxine (T(4)) at 21 days (+60, +91 and +68%, respectively, P < 0.05), while the opposite was observed at 180 days regarding thyroid hormones (T(3), -10%; and T(4), -30%, P < 0.05), with no difference in TSH levels. In hypothalamus, no change was observed in the leptin signalling pathway at 21 days. However, lower janus thyrosine kinase 2 (JAK2) and phosphorilated-signal transducer and activator of transcription-3 (p-STAT3) content were detected in adulthood. In pituitary, the SL group presented higher leptin receptors (Ob-R), JAK2 and p-STAT3 content at 21 days and lower JAK2 and STAT3 content at 180 days old. In contrast, in thyroid, the Ob-R expression was lower in young SL rats, while the adult SL group presented higher Ob-R and JAK2 content. We showed that postnatal EO induces short- and long-term effects upon the hypothalamic-pituitary-thyroid axis. These changes may help to explain future development of metabolic and endocrine dysfunctions, such as metabolic syndrome and hypothyroidism.
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PMID:Postnatal early overnutrition changes the leptin signalling pathway in the hypothalamic-pituitary-thyroid axis of young and adult rats. 1948 48

There is a conserved mechanism in all living organisms whereby overnutrition negatively regulates lifespan, while loss of function mutations in the genes encoding insulin/IGF-1 signaling molecules also independently shorten lifespan in worms and flies. However, in mammals, same mutations sometimes result in severe metabolic disorders and shorter lifespan, although knockout mice with disruption of some insulin/IGF-1 signaling molecules display prolonged lifespan. Moreover, obesity-induced diabetes and metabolic syndrome are also associated with shorter lifespan despite the decreased insulin signaling in liver and skeletal muscle. This is presumably because hyperinsulinemia in obese animals and humans enhances insulin signaling in particular tissues which determine aging and longevity. It is also likely that overnutrition suppresses AMP kinase and increase mTOR activity, contributing to the shorter lifespan in obese subjects.
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PMID:[The mechanisms whereby insulin/IGF-1 signaling regulates aging and longevity]. 1959 Dec 78

Overnutrition and inactivity can lead to obesity, impaired glucose tolerance, dyslipidemia, and hypertension, a cluster of diseases known as the metabolic syndrome. Insulin resistance and dysregulation of adipocytokines are the fundamentals of this syndrome. It is well documented that advancing age is associated with increased body fat and blunted insulin action, however, centenarians, who are the best model of successful aging, had a preserved insulin sensitivity and better adipocytokine profiles. It is also demonstrated that adipocytokine dysregulation can lead sarcopenia and frailty in the oldest old. These observations suggested that preservation of adipose endocrine function by means of lifestyle modification may be potentially important for maintaining health and function and promoting survival at an extremely old age.
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PMID:[The metabolic syndrome; a target for antiaging medicine]. 1959 Dec 96

Obesity, type 2 diabetes, and the associated metabolic syndrome are known as the aggregate products from nutritional excess, and have become huge epidemics and represent public health problems in the developed world. Yet, there exist few successful approaches for the treatment and prevention of these complex diseases, in part because they are not well understood at the molecular levels. Recent research has revealed that many nutrient- and pathogen-sensing systems can be highly integrated, positing the regulatory system of immune response at the mechanistic interface between metabolic regulation and the development of overnutrition-related diseases. The underlying molecular processes have been associated with the basis of how nutritional changes trigger atypical inflammation and how metabolic inflammation affects the signaling and functions of metabolic tissues and cells. In this endeavor, the pro-inflammatory axis consisting of the nuclear transcription factor NFkappaB and its upstream kinase IKKbeta has been identified as one critical mediator that is responsible for nutritionally-induced inflammation, and a large body of research has been documented to support the concept that IKKbeta/NFkappaB represents a general cause of various metabolic dysfunctions under overnutrition. Here, we comparatively review the tissue-specific programs and actions of IKKbeta/NFkappaB in causing and promoting overnutrition-related diseases.
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PMID:NFkappaB-mediated metabolic inflammation in peripheral tissues versus central nervous system. 1963 16

Worldwide, not only the prevalence of obesity has increased dramatically throughout the last three decades but also the incidences of co-morbid conditions such as diabetes type 2 and liver disease have increased. The 'hepatic manifestation of the metabolic syndrome' is called nonalcoholic fatty liver disease (NAFLD) and comprises a wide spectrum of stages of liver disease ranging from simple steatosis to liver cirrhosis. NAFLD of different stages is found in approximately 30% of adults and approximately 20% in the US population. Not just a general overnutrition but also an elevated intake of certain macronutrients such as fat and carbohydrates and herein particularly fructose has been claimed to be risk factors for the development for NAFLD; however, the etiology of this disease is still unknown. The present review outlines some of the potential mechanisms associated with the development of NAFLD and fructose intake with a particular focus on the role of the intestinal barrier functions.
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PMID:Dietary fructose and intestinal barrier: potential risk factor in the pathogenesis of nonalcoholic fatty liver disease. 1967 62

Recent major increases in obesity and related metabolic diseases (known as the metabolic syndrome (MetS)) because of sedentary lifestyles and overnutrition in developed and developing countries, are an exploding medical and social problem. These conditions are associated with increased risk of cardiovascular disease (CVD), the leading cause of death. Thus, it is necessary to understand the molecular basis underlying MetS and develop effective preventive and therapeutic approaches against CVD. To date, 7 angiopoietin-like proteins (Angptls) that are structurally similar to angiopoietins have been identified. However, none binds to the angiopoietin receptor, Tie2, or to the closely related Tie1 receptor, suggesting that these ligands function differently from angiopoietins. Some Angptls potently regulate angiogenesis, similar to angiopoietins, whereas others have pleiotropic activity other than angiogenesis and function in lipid and energy metabolism. In this review, we focus on the roles of Angptl2 and Angptl6/angiopoietin-like growth factor (AGF) in the development of MetS and CVD, and discuss the potential for Angptl2 and Angptl6/AGF to function as molecular targets for the prevention and treatment of both conditions.
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PMID:Angiopoietin-like proteins--potential therapeutic targets for metabolic syndrome and cardiovascular disease. 1987 97


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