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

Pretibial mucin deposition on the shins is known as pretibial myxoedema. We report three patients with pretibial mucinosis without thyroid disease. The patients were characterized clinically by morbid obesity and bilateral lower extremity pitting oedema with gradual and painless onset, and that did not involve the feet and ankles. Vesicles, semitranslucent papules or a woody plaque were found on the shins. Histologically, patients showed characteristic features of epidermal atrophy with effacement of the rete ridge pattern, separation of collagen bundles associated with oedema with stellate to linear fibroblasts, upward-running increased capillary and small vessels with haemosiderin deposition, and mucin deposition at the superficial papillary dermis and around the vessels. We propose that the present cases of 'chronic obesity lymphoedematous mucinosis' belong to the clinical entity of pretibial mucinosis.
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PMID:Chronic obesity lymphoedematous mucinosis: three cases of pretibial mucinosis in obese patients with pitting oedema. 1640 11

Low birth weight is an important cause of infant mortality and morbidity worldwide. Birth weight has been shown to be inversely correlated with adult complex diseases such as obesity, type-2 diabetes and cardiovascular disease. However, little is known about the genetic factors influencing variation in birth weight and its association with diseases that occur in later life. We, therefore, have performed a genome-wide search to identify genes that influence birth weight in Mexican-Americans using the data from the San Antonio Family Birth Weight Study participants (n=840). Heritability of birth weight was estimated as 72.0+/-8.4% (P<0.0001) after adjusting for the effects of sex and term. Multipoint linkage analysis yielded the strongest evidence for linkage of birth weight (LOD=3.7) between the markers D6S1053 and D6S1031 on chromosome 6q. This finding has been replicated (LOD=2.3) in an independent European-American population. Together, these findings provide substantial evidence (LOD(adj)=4.3) for a major locus influencing variation in birth weight. This region harbors positional candidate genes such as chorionic gonadotropin, alpha chain; collagen, type XIX, alpha-1; and protein-tyrosine phosphatase, type 4A, 1 that may play a role in fetal growth and development. In addition, potential evidence for linkage (LOD>or=1.2) was found on chromosomes 1q, 2q, 3q, 4q, 9p, 19p and 19q with LODs ranging from 1.3 to 2.7. Thus, we have found strong evidence for a major gene on chromosome 6q that influences variation in birth weight in both Mexican- and European-Americans.
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PMID:A quantitative trait locus (QTL) on chromosome 6q influences birth weight in two independent family studies. 1661 75

Insulin resistance and the consequent metabolic disorders are associated with a state of platelet hyperactivity. Oxidative stress is responsible for the persistent platelet activation. We sought to study the inhibitory effect of cardiotonic pills, an oral herbal component, on platelet function in a dog model with insulin resistance induced by high-fat feeding. We fed 18 dogs with a high-fat diet and six dogs with normal chow as control for 6 months. Then, six dogs were fed with a high-fat diet and received additional aspirin (250 mg/day), and another six dogs received additional cardiotonic pills (1,000 mg/day) for 4 months. Time-course changes in metabolic parameters and platelet function were detected. After high-fat feeding for 6 months, 18 dogs developed a series of metabolic disorders including obesity, dyslipidemia, oxidative stress and insulin resistance. In addition, a platelet hyperactivity state, characterized by increased agonist (arachidonic acid, ADP and collagen) induced platelet aggregation, platelet expression of adhesion molecules (P-selectin and GP IIb/IIIa), and platelet intracellular calcium concentration, was indicated. Cardiotonic pills showed a significant antioxidative activity by presenting an increase in plasma superoxide dismutase and decrease in erythrocyte glutathione, as well as a lipid-lowering effect (decrease in both plasma cholesterol and triglyceride). Either aspirin or cardiotonic pills could significantly reverse the platelet hypersensitivity and hyperfunction. Compared with aspirin, cardiotonic pills showed a more exaggerated inhibitory effect on platelet function (a significantly decreased collagen-stimulated platelet aggregation, and expression of adhesion molecules). In conclusion, cardiotonic pills inhibited platelet hyperfunction in dogs with insulin resistance. This inhibitory effect may mainly be explained by antioxidative activity and metabolic control.
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PMID:Inhibitory effects of cardiotonic pills on platelet function in dogs fed a high-fat diet. 1665 67

The obesity-prone/obesity-resistant rat model has been used to study mechanisms responsible for obesity-related abnormalities in renal function and blood pressure, but whether this model exhibits cardiac dysfunction has not been determined. We tested the hypothesis that obesity-prone rats would display cardiovascular abnormalities seen in other diet-induced obese models (ie, hypertension, tachycardia, left ventricular hypertrophy, increased collagen deposition, reduced cardiac contractility, and increased end diastolic pressure). Male Sprague-Dawley rats were fed a control diet or a moderate fat diet containing 32% kcal as fat while hemodynamics were continuously monitored using telemetry. After 12 weeks, obesity-prone rats were significantly heavier and had greater body fat compared with obesity-resistant rats and controls, but daily (20 hours/d) averages and diurnal rhythms of blood pressure and heart rate did not differ among groups. Echocardiographic indices of cardiac structure and function, histological evidence of cardiac collagen, and directly measured heart weights did not differ among groups. Peak left ventricular pressure, end diastolic pressure, +dP/dt, and -dP/dt were also not significantly different among groups. Plasma cholesterol and hepatic cholesterol were significantly higher in obesity-prone rats compared with obesity-resistant rats and controls; hepatic triglycerides were higher in obesity-prone rats compared with controls (P< or =0.05). Leptin was significantly higher in obesity-prone rats compared with controls and across all groups was significantly correlated with body fat (P< or =0.05). These results suggest that 12 weeks of a moderate fat diet in the obesity-prone/obesity-resistant rat model induced lipid and endocrine abnormalities typical of obesity but was not sufficient to cause significant cardiac abnormalities.
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PMID:Cardiovascular function in a rat model of diet-induced obesity. 1670 91

Epidemiological studies indicate that obesity, insulin resistance, and diabetes are important comorbidities of patients with ischemic heart disease and increase mortality and development of congestive heart failure after myocardial infarction. Although ob/ob and db/db mice are commonly used to study obesity with insulin resistance or diabetes, mutations in the leptin gene or its receptor are rarely the cause of obesity in humans, which is, instead, primarily a consequence of dietary and lifestyle factors. Therefore, we used a murine model of diet-induced obesity to examine the physiological effects of obesity and the inflammatory and healing response of diet-induced obese (DIO) mice after myocardial ischemia-reperfusion injury. DIO mice developed hyperinsulinemia and insulin resistance and hepatic steatosis, with significant ectopic lipid deposition in the heart and cardiac hypertrophy in the absence of significant changes in blood pressure. The mRNA levels of chemokines at 24 h and cytokines at 24 and 72 h of reperfusion were higher in DIO than in lean mice. In granulation tissue at 72 h of reperfusion, macrophage density was significantly increased, whereas neutrophil density was reduced, in DIO mice compared with lean mice. At 7 days of reperfusion, collagen deposition in the scar was significantly reduced and left ventricular (LV) dilation and cardiac hypertrophy were increased, indicative of adverse LV remodeling, in infarcted DIO mice. Characterization of a murine diet-induced model of obesity and insulin resistance that satisfies many aspects commonly observed in human obesity allows detailed examination of the adverse cardiovascular effects of diet-induced obesity at the molecular level.
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PMID:Effects of diet-induced obesity on inflammation and remodeling after myocardial infarction. 1673 44

Obesity is a well-established risk factor for congestive heart failure. Evidence has been provided indicating that insulin resistance could be the mediator between obesity and congestive heart failure, but the pathogenic mechanisms leading to myocardial alterations remain unclear. The aim of this study was to investigate, by ultrasonic integrated backscatter (IBS) analysis, subclinical alterations of left ventricular (LV) structure and function in severe obesity. Sixty consecutive, severely obese people, who were otherwise healthy (15 men, 45 women; mean age +/- SD = 31.8 +/- 7 years), were enrolled. A total of 48 sex- and age-matched nonobese healthy participants were recruited as control subjects. All participants underwent conventional 2-dimensional color Doppler echocardiography, pulsed wave Doppler tissue imaging at mitral annulus level, and IBS. The homeostasis model assessment insulin resistance index was used to assess insulin resistance; the index values in the obese group were significantly higher (mean +/- SD = 4.9 +/- 1.4) than in the control group (0.92 +/- 0.5, P < .0001). Obese patients had a greater LV mass index by height (58.5 +/- 14 g/m(2.7)) than did control subjects (37 +/- 8 g/m(2.7), P < .0001) because of compensation response to volume overload caused by a greater cardiac output (P < .02). Preload reserve was increased in obese patients, as demonstrated by the significant increase in left atrial dimension (P < .0001). This volumetric increase activated the Frank-Starling mechanism, and determined a significantly higher LV ejection fraction (P < .03) in obese patients as compared with control subjects. A slightly reduced LV diastolic function was demonstrated in obese patients (transmitral early to late peak diastolic transmitral flow velocities ratio = 1.1 +/- 0.7) as compared with control subjects (1.5 +/- 0.5, P < .02). Pulsed wave Doppler tissue imaging showed an impairment of diastolic LV longitudinal function and increased LV diastolic filling pressure. The IBS values at septum level, indexed by pericardium interface, were significantly higher for septum in the obese group (57.8 +/- 8%) than in the control group (42.3 +/- 9%, P < .0001). Additional IBS alterations were observed in the obese group, with a significantly lower cyclic variation index both at septum (P < .0001) and at posterior wall (P < .001) levels. A significant association was found between insulin resistance index and both the IBS index of myocardial reflectivity at septum level (expression of increased myocardial collagen content) or LV mass. In conclusion, this study demonstrates that obese patients exhibit myocardial structural and functional alterations related to insulin resistance and to LV volume overload, which could be considered the very early stage of incipient obesity cardiomyopathy.
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PMID:Obesity cardiomyopathy: is it a reality? An ultrasonic tissue characterization study. 1688 Jan 4

Leptin is a peptide hormone that is mainly, but not exclusively, produced in adipose tissue and plays a pivotal role in regulating food intake and energy expenditure. Besides its effects on regulation of body weight, appetite and energy expenditure, leptin exhibits influence on the immune system and may contribute to the deterioration of renal function. These direct and indirect renal effects of leptin could partly explain obesity-associated kidney disease and may be also relevant for diabetic nephropathy in type 2 diabetes. Leptin is primarily metabolized in the kidney, presumably by binding to megalin, a multiligand receptor in the proximal tubule, tubular uptake and endocytosis. The kidney expresses abundant concentrations of the small isoform of the leptin receptor (Ob-Ra). In cultured renal rat endothelial cells and mesangial cells obtained from db/db mice, leptin can signal through the Ob-Ra receptor isoform. The peptide stimulates proliferation of glomerular endothelial cells, increases TGF-beta1 synthesis, and collagen type IV production. In contrast, leptin did not influence TGF-beta1 production in mesangial cells, but the peptide stimulates glucose transport in these cells, increased collagen type I synthesis, and lead to an upregulation of surface TGF-beta type II receptors through signal transduction pathways involving phosphatidylinositol-3-kinase. Leptin also stimulates hypertrophy, but not proliferation in cultured rat mesangial cells. Infusion of leptin for 3 weeks into normal rats fosters development of glomerulosclerosis and proteinuria. In addition, transgenic mice with leptin overexpression demonstrated a increase in collagen type IV and fibronectin mRNA in the kidney. Additional previously described direct and indirect effects of leptin on the kidney include natriuretic effects, an increase in sympathetic nervous activity, and stimulation of reactive oxygen species. These findings collectively suggest that the kidney is a target organ for leptin and that this hormone might play an important role in renal pathophysiology.
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PMID:Leptin and renal fibrosis. 1692 41

The effects of leptin, in concentrations seen in obesity, on collagen production and turnover in non-immortalized human hepatic stellate cell (HSC), were unknown. The profibrogenic effects of leptin in these cells were studied. Hepatic stellate cells were obtained from resected livers. Collagen I/III gene expression and protein production were measured by quantitative real-time polymerase chain reaction and sodium dodecyl sulfate-polyacrylamide gel electrophoresis, respectively. The signal transduction pathways involved were evaluated by specific blockers of the phosphatidylinositol 3-kinase (PI3K), mitogen-activated protein kinase kinase (MEK), and Janus kinase 2 (JAK2). The effects on matrix metalloproteinase 1 (MMP-1) and tissue inhibitor of metalloproteinase 1 (TIMP-1) were assessed by their gene transcript levels, collagenolytic activity of cell culture supernatants, and MMP-1 protein levels. At concentrations seen in nonobese individuals ([leptin] < 10 ng/mL), leptin did not affect collagen production. At concentrations seen in obesity (30-50 ng/mL), leptin increased collagen I and III messenger RNA (mRNA) transcript levels by 286% +/- 55% (P < .001) and 167% +/- 62% (P < .007) and protein production by 45.8% +/- .02% and 84.39% +/- .01%, respectively. These effects were blocked by JAK2 inhibition as well as PI3K inhibition. Although MEK inhibition blocked leptin-induced procollagen I and III mRNA levels, there were no significant effects on collagen I and III protein levels. Leptin (10-50 ng/mL) had no significant effects on MMP-1 or TIMP-1 mRNA levels, collagenolytic activity, or MMP-1 protein levels. In conclusion, leptin, at levels seen in obese individuals, produces an increase in collagen production by HSC acting through the JAK and PI3K pathways. At these concentrations, leptin does not affect MMP-1 or TIMP-1 expression or collagenolytic activity of HSC.
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PMID:Physiologic concentrations of leptin increase collagen production by non-immortalized human hepatic stellate cells. 1697 1

Type 2 diabetes (DM-2) has become a major global health problem that has been fueled mainly by increasing obesity and aging of the population. Most studies show that arterial stiffening occurs across all age groups in both type 1 diabetes and DM-2, and among those with impaired fasting glucose, impaired glucose tolerance, and the metabolic syndrome. Arterial stiffening in DM-2 results, in part, from the clustering of hyperglycemia, dyslipidemia and hypertension, all of which may promote insulin resistance, oxidative stress, endothelial dysfunction, and the formation of pro-inflammatory cytokines and advanced glycosylation end-products. Likewise, aging may increase arterial stiffening by altering the proportions of elastin and collagen in the aorta. The consequences of arterial stiffening are increased pulse pressure, hypertension, and a greater risk of cardiovascular disease. Treatment strategies to reduce or prevent arterial stiffening include pharmacologic agents that block the renin-angiotensin-aldosterone system, relax vascular smooth muscle, enhance release of nitric oxide from endothelial cells, and break glycosylation end-product cross-links, and fish oil supplementation.
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PMID:Diabetes and arterial stiffening. 1707 13

The potential role of placental growth factor (PlGF) in early stages of adipogenesis was investigated in vivo using a murine model of obesity, as well as in vitro using cultured preadipocytes. PlGF-deficient (PlGF-/-) and wild-type (WT) mice, kept on high fat diet (HFD) for 3 weeks, had comparable body weight and weight of subcutaneous (SC) and gonadal (GON) adipose tissues. Blood vessel size and blood vessel density, normalized to adipocyte number, were not significantly different in SC and GON adipose tissues of both genotypes. Differentiation of embryonic fibroblasts derived from WT or PlGF-/- mice into mature adipocytes was comparable. Furthermore, addition of recombinant PlGF, of the PlGF neutralizing MAb PL5D11D4 or of the anti-Flk-1 MAb DC101 to cultured 3T3-F442A preadipocytes did not significantly affect their differentiation into mature adipocytes. Ex vivo blood vessel outgrowth following seeding of adipose tissue-derived microvessel fragments in 3D-collagen gels was not affected by PlGF deficiency. Thus, in murine model systems, PlGF does not seem to play an important role in early adipogenesis.
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PMID:On the role of placental growth factor in murine adipogenesis. 1713 43


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