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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Hypertension that occurs before the age of 60 years is strongly aggregated in families, mostly due to genetic factors with weaker contributions from a shared family environment. Hypertension is probably a heterogeneous collection of overlapping subsets of pathophysiological mechanisms, such as dyslipidemia, obesity, hyperinsulinemia and cation metabolism. Highly heritable traits such as sodium-lithium countertransport, urinary kallikrein excretion and a body fat pattern index show evidence of major gene segregation in families with hypertension. They are thought to be intermediate phenotypes in the chain of pathophysiological events leading from specific genes to the distant phenotype of hypertension. They provide evidence of measurable contributions from single gene traits to the susceptibility to hypertension. Genetic linkage studies have suggested that other specific loci (e.g. histocompatibility leukocyte antigen, blood group MN and the haptoglobin protein) contribute to the susceptibility to hypertension. DNA sequencing has shown a point mutation for lipoprotein lipase that conveys susceptibility to lipid abnormalities, and possibly also hypertension, as seen in families with dyslipidemic hypertension. Further application of these approaches, especially in families that include multiple siblings with hypertension, shows promise of a true understanding of how the combined effects of a few specific genes, the polygenic background and selected environmental factors can lead to essential hypertension. This understanding should foster better tailored and more effective approaches to the prevention, diagnosis and treatment of hypertension.
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PMID:Multigenic human hypertension: evidence for subtypes and hope for haplotypes. 209 95

Human arterial hypertension is likely a multifactorial trait resulting from multiple measurable monogenes, blended polygenes, shared family environment, and individual environment. Familial aggregation of hypertension and familial correlation of blood pressure appears to be more due to genes than to shared family environment. Total genetic heritability of 80% with some recessive major gene effects have been found for several traits associated with hypertension including urinary kallikrein excretion, intraerythrocytic sodium, and sodium-lithium countertransport. Other interesting factors regarding hypertension genetics include: non-modulation of the renin angiotensin system, intralymphocytic sodium, ionized calcium, and several genetic markers such as haptoglobin, HLA, and MNS blood type. Probably the most clinically useful information regarding the genetics of hypertension is evolving in several studies reporting a strong association of hypertension with dyslipidemia, diabetes, and obesity.
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PMID:Genetics of hypertension: what we know and don't know. 220 56

Type 2 (non-insulin-dependent) diabetes mellitus, a disease of complex aetiology, has been reported to be nonrandomly associated with several polymorphic markers in human populations. These data, plus evidence of a high prevalence of Type 2 diabetes mellitus in American Indians and mixed populations, such as Mexican-Americans, which is only partially attributable to the prevalence of obesity in these populations, makes it imperative that the nature of such associations be clarified in relation to genetic susceptibility to Type 2 diabetes mellitus. The present paper reports the results of tests of association between Type 2 diabetes mellitus and seven polymorphic markers: the blood groups - ABO, Rhesus, Duffy and Kell (K and KP) - haptoglobin and group specific component; among Anglo and Hispanic populations in the San Luis Valley of Colorado, USA. The sample population consisted of 788 individuals of which 398 were Anglo subjects (97 Types 2 diabetes mellitus patients and 301 normal individuals) and 390 Hispanic subjects (191 Type 2 diabetes mellitus patients and 199 normal individuals). Association between Type 2 diabetes mellitus and genetic markers in patients was tested using the G2 statistic within each ethnic class using normal frequencies as a comparison. Results of the tests indicated that only the Kell blood group was significantly associated with Type 2 diabetes mellitus at a 5% level among the Anglo subjects (G2 = 5.16, 1df). This significant value can be explained by chance alone, if multiple comparisons are taken into account. Our tests have not shown the previously reported haptoglobin or Rhesus blood group associations seen in Mexican-Americans in San Antonio, Texas.
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PMID:Genetic studies of type 2 (non-insulin-dependent) diabetes mellitus: lack of association with seven genetic markers. 279 88

The serum viscosity of diabetic patients has been found to be increased. The elevation averaged 8% above healthy subjects and 6% above nondiabetic patients. The serum viscosity elevation was greater when diabetic sequelae associated with microangiopathy were present. No relation of serum viscosity to age, sex, obesity, duration of disease, or type of treatment was demonstrated. Serum total protein and glucose levels were found to be correlated with serum viscosity, and increases in their serum concentrations were observed in diabetes. Analysis demonstrated that their elevation did not explain either the viscosity increase or the difference in viscosity between diabetics with and without sequelae.Intrinsic viscosity, abbreviated [eta], is a concentration-independent solute property related to molecular shape. [eta] was found to be 7% higher in diabetic than in normal serum. The [eta] difference accounted for at least half of the serum viscosity elevation. The rest of the increase was due to increased serum protein level and increased nonprotein solids, presumably glucose and lipid. Associated with increased [eta] was a decline in albumin: globulin ratio and elevation of the acute phase reactant proteins, alpha(1)-acid glycoprotein, alpha(1)-antitrypsin, haptoglobin, and ceruloplasmin. Studies comparing diabetic and normal serum fractionated by using 21.5% sodium sulfate showed that changes in [eta] were attributable to changes in serum protein composition rather than an inherent qualitative disturbance of protein present in one of the fractions. Since serum viscosity is elevated in early diabetes, it may be a part of the metabolic disturbance of diabetes and could play a role in the development of diabetic microangiopathy.
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PMID:Disturbance of serum viscosity in diabetes mellitus. 420 23

Increase in adipose mass results in obesity and modulation of several factors in white adipose tissue (WAT). Two important examples are tumor necrosis factor alpha (TNFalpha) and leptin, both of which are upregulated in adipose tissue in obesity. In order to isolate genes differentially expressed in the WAT of genetically obese db/db mice compared to their lean littermates, we performed RNA fingerprinting and identified haptoglobin (Hp), which is significantly upregulated in the obese animals. Hp is a glycoprotein induced by a number of cytokines, LPS (Lipopolysaccharide), and more generally by inflammation. A significant upregulation of WAT Hp expression was also evident in several experimental obese models including the yellow agouti (/) A(y), ob/ob and goldthioglucose-treated mice (10-, 8-, and 7-fold, respectively). To identify the potential signals for an increase in Hp expression in obesity, we examined leptin and TNFalpha in vivo. Wild type animals treated with recombinant leptin did not show any alteration in WAT Hp expression compared to controls that were food restricted to the level of intake of the treated animals. On the other hand, Hp expression was induced in mice transgenically expressing TNFalpha in adipose tissue. Finally, a significant downregulation of WAT Hp mRNA was observed in ob/ob mice deficient in TNFalpha function, when compared to the ob/ob controls. These results demonstrate that haptoglobin expression in WAT is increased in obesity in rodents and TNFalpha is an important signal for this regulation.
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PMID:Obesity modulates the expression of haptoglobin in the white adipose tissue via TNFalpha. 1180 29

Recently we found that interleukin-6 (IL-6) knockout mice develop mature-onset obesity and that a single intracerebroventricular (ICV) injection of IL-6 increases energy expenditure. In the present study we investigated if chronic ICV treatment with IL-6 can suppress body fat mass. IL-6 was injected ICV daily for two weeks to rats fed a high-fat diet. IL-6 treatment but not saline treatment decreased body weight by 8.4% and decreased the relative weights of mesenteric and retroperitoneal fat pads. Consistent with this, circulating leptin levels were decreased by 40% after IL-6 treatment but not after saline treatment. Average food intake per day was decreased in the IL-6 treated group compared to the saline treated rats. IL-6 treatment did not change hepatic expression of the acute-phase protein haptoglobin, serum levels of insulin or insulin-like growth factor-I, or the weights of the heart, liver, kidneys, adrenals, and spleen. We conclude that centrally administered IL-6 can decrease body fat in rats without causing acute-phase reaction.
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PMID:Intracerebroventricular interleukin-6 treatment decreases body fat in rats. 1205 38

The 3T3-L1 cell line is a well-established and commonly used in vitro model to assess adipocyte differentiation. Over the course of several days confluent 3T3-L1 cells can be converted to adipocytes in the presence of an adipogenic cocktail. Changes in gene expression were measured by DNA microarrays at three time points (24 h, 4 days, and 1 week) during the course of differentiation from preadipocytes to mature adipocytes. Several functional categories of genes were affected by adipocyte conversion. In addition, seven genes were found to be commonly altered by 5-fold or more by adipocyte conversion at all three time points. Lipocalin 2, haptoglobin, serum amyloid A3, stearoyl-CoA desaturase, and 11beta-hydroxysteroid dehydrogenase 1 were induced while actin alpha2 and procollagen VIII alpha1 were suppressed by adipocyte differentiation. Further study of the regulation of these genes and pathways will lead to an increased understanding of the biochemical pathways involved in adipocyte differentiation and possibly to the identification of new therapeutic targets for treatment of obesity and other metabolic diseases.
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PMID:Expression profiling during adipocyte differentiation of 3T3-L1 fibroblasts. 1245 56

Cross-sectional studies have associated obesity and other components of the so-called metabolic syndrome with low-grade inflammation. The temporal and causal relations of this association have not been fully explored. This study explored whether elevated levels of inflammation-sensitive plasma proteins (ISPs) (fibrinogen, orosomucoid, alpha1-antitrypsin, haptoglobin, and ceruloplasmin) are associated with future weight gain. Five ISPs were measured in 2,821 nondiabetic healthy men (38-50 years of age) who were reexamined after a mean follow-up of 6.1 years. Future weight gain was studied in relation to the number of elevated ISPs (i.e., in the top quartile). The proportion with a large weight gain (75th percentile >/= 3.8 kg) was 21.0, 25.9, 26.8, and 28.3%, respectively, among men with none, one, two, and three or more ISPs in the top quartile (P for trend 0.0005). This relation remained significant after adjustments for weight at baseline, follow-up time, height (at baseline and follow-up), physical inactivity (at baseline and follow-up), smoking (at baseline and follow-up), high alcohol consumption, and insulin resistance. The relations were largely similar for all individual ISPs. Elevated ISP levels predict a large weight gain in middle-aged men. This relation could contribute to the relation between inflammation, the metabolic syndrome, and cardiovascular disease.
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PMID:Inflammation-sensitive plasma proteins are associated with future weight gain. 1288 28

Adipose tissue plays an active role in energy balance because it is not only a lipid storing and mobilizing tissue but consists of functionally specialized tissues able to produce heat (in brown adipose tissue) and to produce or release a vast number of so called adipokines or adipocytokines. These consist of polypeptides but also non-protein factors and are metabolically active molecules belonging to different functional categories like immunity (complement factors, haptoglobin), endocrine function (leptin, sex steroids, various growth factors), metabolic function (fatty acids, adiponectin, resistin), and cardiovascular function (angiotensinogen, PAI-1). Recent advances using genomic and proteomic approaches have identified numerous new adipocyte secreted factors whose function remain to be established. Too little as well as too much adipose tissue leads to metabolic disturbances like insulin resistance. Visceral obesity is especially strongly correlated with the development of diabetes, hypertension and cardio-vascular disease. Thermogenesis in brown adipose tissue is a means to dissipate excess energy, but in adult humans brown fat is very scarce and probably not functional. However, human white adipose tissue contains mesenchymal stem cells, and if these could be stimulated to differentiate into brown adipocytes, increased energy expenditure in white fat could help to shift energy balance towards a more negative state.
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PMID:Adipose tissue as a regulator of energy balance. 1505 10

White adipose tissue is now recognised to be a multifunctional organ; in addition to the central role of lipid storage, it has a major endocrine function secreting several hormones, notably leptin and adiponectin, and a diverse range of other protein factors. These various protein signals have been given the collective name 'adipocytokines' or 'adipokines'. However, since most are neither 'cytokines' nor 'cytokine-like', it is recommended that the term 'adipokine' be universally adopted to describe a protein that is secreted from (and synthesised by) adipocytes. It is suggested that the term is restricted to proteins secreted from adipocytes, excluding signals released only by the other cell types (such as macrophages) in adipose tissue. The adipokinome (which together with lipid moieties released, such as fatty acids and prostaglandins, constitute the secretome of fat cells) includes proteins involved in lipid metabolism, insulin sensitivity, the alternative complement system, vascular haemostasis, blood pressure regulation and angiogenesis, as well as the regulation of energy balance. In addition, there is a growing list of adipokines involved in inflammation (TNFalpha, IL-1beta, IL-6, IL-8, IL-10, transforming growth factor-beta, nerve growth factor) and the acute-phase response (plasminogen activator inhibitor-1, haptoglobin, serum amyloid A). Production of these proteins by adipose tissue is increased in obesity, and raised circulating levels of several acute-phase proteins and inflammatory cytokines has led to the view that the obese are characterised by a state of chronic low-grade inflammation, and that this links causally to insulin resistance and the metabolic syndrome. It is, however, unclear as to the extent to which adipose tissue contributes quantitatively to the elevated circulating levels of these factors in obesity and whether there is a generalised or local state of inflammation. The parsimonious view is that the increased production of inflammatory cytokines and acute-phase proteins by adipose tissue in obesity relates primarily to localised events within the expanding fat depots. It is suggested that these events reflect hypoxia in parts of the growing adipose tissue mass in advance of angiogenesis, and involve the key controller of the cellular response to hypoxia, the transcription factor hypoxia inducible factor-1.
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PMID:Adipokines: inflammation and the pleiotropic role of white adipose tissue. 1546 38


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