Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0004153 (atherosclerosis)
 77,401 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Leptin is an adipocytokine that is produced mainly by adipose tissue; it is also identified in atherosclerotic lesions in human coronary atherosclerosis. However, the relation of serum leptin concentrations to ischemic heart disease (IHD) is still obscure. The aims of the present study were to investigate serum leptin concentrations in patients with ST-elevated myocardial infarction (STEMI) and with chronic stable angina pectoris (CSAP) and to evaluate the possible correlations of leptin to other atherosclerotic risk factors; including serum high sensitive C-reactive protein (Hs-CRP), serum homocysteine, and fibrinogen concentrations. For this purpose, 35 patients with CSAP, 40 with acute STEMI, and 30 control subjects with normal findings from coronary angiography were taken into the study prospectively. Serum leptin concentrations were significantly higher in patients with CSAP and STEMI compared to the control group (7.74 +/-1.34 vs 6.37 +/-1.85 ng/mL, p=0.021 and 8.22 +/-3.13 vs 6.37 +/-1.85 ng/mL, p=0.023, respectively). In addition, serum homocysteine concentrations were significantly increased in patients with CSAP (15.23 +/-5.96 vs 11.40 +/-2.11 micromol/L, p=0.025) and patients with STEMI (15.90 +/-5.02 vs 11.40 +/-2.11 micromol/L, p=0.012) compared to the control group. Serum fibrinogen concentrations were significantly increased only in the CSAP group as compared to controls (4.15 +/-1.39 vs 3.45 +/-1.19 g/L, p=0.025). No significant correlation was found between leptin levels and selected risk factors. In conclusion, serum leptin concentrations were significantly higher in both the CSAP and STEMI groups. However, owing to the lack of correlation between the leptin levels and selected classical coronary risk factors, it may be considered that leptin can be evaluated as one of the independent risk factors for IHD. Further randomized and controlled studies will be required to determine the pathophysiological meaning of the increased leptin levels and the central role between adipocyte function and atherosclerosis.
 ...
PMID:Increased serum leptin concentrations in patients with chronic stable angina pectoris and ST-elevated myocardial infarction. 1670 86

Adipose tissue plays a critical role in energy homeostasis, not only in storing triglycerides, but also responding to nutrient, neural, and hormonal signals and secreting adipokines that control feeding, thermogenesis, immunity, and neuroendocrine function. A rise in leptin signals satiety to the brain through receptors in hypothalamic and brainstem neurons. Leptin activates tyrosine kinase, Janus kinase 2, and signal transducer and activator of transcription 3, leading to increased levels of anorexigenic peptides, e.g., alpha-melanocyte stimulating hormone and cocaine- and amphetamine-regulated transcript, and inhibition of orexigenic peptides, e.g., neuropeptide Y and agouti-related peptide. Obesity is characterized by hyperleptinemia and hypothalamic leptin resistance, partly caused by induction of suppressor of cytokine signaling-3. Leptin falls rapidly during fasting and potently stimulates appetite, reduces thermogenesis, and mediates the inhibition of thyroid and reproductive hormones and activation of the hypothalamic-pituitary-adrenal axis. These actions are integrated by the paraventicular hypothalamic nucleus. Leptin also decreases glucose and stimulates lipolysis through central and peripheral pathways involving AMP-activated protein kinase (AMPK). Adiponectin is secreted exclusively by adipocytes and has been linked to glucose, lipid, and cardiovascular regulation. Obesity, diabetes, and atherosclerosis have been associated with reduced adiponectin levels, whereas adiponectin treatment reverses these abnormalities partly through activation of AMPK in liver and muscle. Administration of adiponectin in the brain recapitulates the peripheral actions to increase fatty acid oxidation and insulin sensitivity and reduce glucose. Although putative adiponectin receptors are widespread in peripheral organs and brain, it is uncertain whether adiponectin acts exclusively through these targets. As with leptin, adiponectin requires the central melanocortin pathway. Furthermore, adiponectin stimulates fatty acid oxidation and reduces glucose and lipids, at least in part, by activating AMPK in muscle and liver.
 ...
PMID:Adipose tissue as an endocrine organ. 1702 75

Obesity is often complicated by hypertension, and both conditions are risk factors for atherosclerosis. Leptin has attracted attention as a possible cause of hypertension in obese persons. We investigated the effect of a slow-release alpha1-receptor blocker, bunazosin hydrochloride, on leptin levels and insulin resistance in obese hypertensive patients with hyperleptinemia. The subjects were 17 patients (12 men and 5 women aged 56.1 +/- 12.2 years) with essential hypertension who were not receiving alpha1-receptor blockers. They had a body mass index (BMI) > or = 25 kg/m2 and a plasma leptin concentration > or = 5 ng/ml. They received oral therapy with bunazosin hydrochloride at doses of up to 9 mg/day. The plasma leptin concentration, body weight, blood pressure, heart rate, fasting blood glucose, plasma insulin concentration, and free fatty acid level were compared between before and after treatment. Although there was no significant change of BMI, there was a significant decrease of plasma leptin after treatment (10.6 +/- 5.4 ng/ml vs. 8.7 +/- 3.4 ng/ml, p = 0.0128), as well as a significant decrease of plasma insulin (9.8 +/- 4.8 microU/ml vs. 8.1 +/- 4.6 microU/ml, p = 0.0494) and HOMA-R (2.9 +/- 2.1 vs. 2.2 +/- 1.5, p = 0.0237). In conclusion, bunazosin hydrochloride reduced the plasma leptin level and improved insulin resistance in hypertensive patients with obesity and hyperleptinemia.
 ...
PMID:An alpha1-receptor blocker reduces plasma leptin levels in hypertensive patients with obesity and hyperleptinemia. 1728 68

Both experimental and epidemiological studies suggest that leptin is one of the molecules responsible for accelerated atherosclerosis in obese humans. To confirm the notion, we studied whether leptin accelerates atherosclerosis in apoE(-/-) mice. Leptin deficient hyperlipidemic mice (ob/ob;apoE(-/-) mice) developed significantly less atherosclerosis than apoE(-/-) mice, when fed an atherogenic diet for 16 weeks from 8 weeks of age. Histological analysis revealed that most of the atherosclerotic lesions in ob/ob;apoE(-/-) mice remained as fatty streaks, while those in apoE(-/-) mice were mainly fibrous plaques. The decrease in atherosclerosis was not due to changes in the serum levels of cholesterol, TNF-alpha, or adiponectin. Exogenous leptin significantly increased atherosclerotic areas in apoE(-/-) mice, even though it decreased food intake and body weight. Our findings support the notion that leptin accelerates atherosclerosis.
Atherosclerosis 2008 Jan
PMID:Leptin deficiency suppresses progression of atherosclerosis in apoE-deficient mice. 1736 69

During managing patients with epilepsy, there is a great risk of weight changes, particularly weight gain with some antiepileptic medications. Weight gain is not only a cosmetic problem that leads to non-compliance to medications but also increases the risk for atherosclerosis and its related complications. The mechanisms underlying weight gain in epilepsy are multiple and controversial and have been attributed to the effect of epilepsy and more commonly the effect of antiepileptic medications on the central and peripheral mechanisms regulating weight homeostasis including the two main homeostatic hormones, leptin, a protein product of obesity gene secreted by adipocytes and insulin, a protein product of pancreatic beta-cells. Increased blood levels of leptin and insulin due to leptin and insulin resistance is observed in patients with epilepsy. Leptin forms an important link between weight gain, insulin resistance, epilepsy and atherosclerosis. The knowledge of the novel roles of leptin in patients with epilepsy will help identification of early markers for the related adverse weight changes, thus allowing proper characterization of suitable antiepileptic medication as initial step during management and follow up of patients.
 ...
PMID:Leptin and insulin homeostasis in epilepsy: relation to weight adverse conditions. 1749 74

The role of leptin in the pathomechanism of atherosclerosis, through its free radical generating ability is established. Its effect however, on the regulation of intracellular cholesterol synthesis has not been studied. The aim of the present study was to elucidate whether leptin influences endogenous cholesterol synthesis in monocytes. Furthermore, leptin signaling to HMG CoA reductase in control and hypercholesterolemic monocytes were compared. The in vitro effect of leptin was studied on freshly isolated human monocytes obtained from healthy control volunteers and patients with hypercholesterolemia. Our results can be summarized as follows: (1) Leptin is able to increase endogenous cholesterol synthesis in human monocytes in vitro. (2) The cholesterol synthesis increasing effect of the hormone is more pronounced in hypercholesterolemic monocytes with high basal cholesterol biosynthesis. (3) The leptin-induced Ca(2+) signal was involved in the enhancement of HMG CoA reductase activation in monocytes from both controls and hypercholesterolemic patients. (4) In control monocytes the Ca(2+) signal originated from intracellular pools, whereas in patients, Ca(2+)-influx and protein kinase C activation were found to be responsible for the leptin-effect. Mevalonate cycle inhibiting fluvastatin and 25-hydroxycholesterol decreased cholesterol production in leptin-stimulated monocytes. Our present study provides the first proof of the cholesterol synthesis enhancing effect of leptin through a statin-sensitive pathway in circulating monocytes. Furthermore our results suggest that leptin can be involved in the pathomechanism of atherosclerotic plaque formation also through its effect on cholesterol biosynthesis in monocytes.
 ...
PMID:Leptin stimulates endogenous cholesterol synthesis in human monocytes: New role of an old player in atherosclerotic plaque formation. Leptin-induced increase in cholesterol synthesis. 1756 Jan 60

Leptin, among the best known hormone markers for obesity, exerts pleiotropic actions on multiple organ systems. In this review, we summarize major leptin signaling pathways, namely Janus-activated kinase/signal transducers and activators of transcription and mitogen-activated protein kinase, including possible mechanisms of leptin resistance in obesity. The effects of leptin on the cardiovascular system are discussed in detail, including its contributions to hypertension, atherosclerosis, depressed myocardial contractile function, fatty acid metabolism, hypertrophic remodeling, and reduction of ischemic/reperfusion injury. The overall goal is to summarize current understanding of how altered leptin signaling in obesity contributes to obesity-related cardiovascular disease.
 ...
PMID:Leptin signaling and obesity: cardiovascular consequences. 1787 73

The metabolic syndrome is a group of disorders including obesity, insulin resistance, atherogenic dyslipidemia, hyperglycemia, and hypertension. To date, few animal models have been described to recapitulate the phenotypes of the syndrome. In this study, we generated and characterized two lines of triple-knockout mice that are deficient in either apolipoprotein E (Apoe(-/-)) or low-density lipoprotein receptor (Ldlr(-/-)) and express no leptin (Lep(ob/ob)) or apolipoprotein B-48 but exclusively apolipoprotein B-100 (Apob(100/100)). These two lines are referred to as Apoe triple-knockout-Apoe 3KO (Apoe(-/-)Apob(100/100)Lep(ob/ob)) and Ldlr triple-knockout-Ldlr 3KO (Ldlr(-/-)Apob(100/100)Lep(ob/ob)) mice. Both lines develop obesity, hyperinsulinemia, hyperlipidemia, hypertension, and atherosclerosis. However, only Apoe 3KO mice are hyperglycemic and glucose intolerant and are more obese than Ldlr 3KO mice. To evaluate the utility of these lines as pharmacological models, we treated both with leptin and found that leptin therapy ameliorated most metabolic derangements. Leptin was more effective in improving glucose tolerance in Ldlr 3KO than Apoe 3KO animals. The reduction of plasma cholesterol by leptin in Ldlr 3KO mice can be accounted for by its suppressive effect on food intake. However, in Apoe 3KO mice, leptin further reduced plasma cholesterol independently of its effect on food intake, and this improvement correlated with a smaller plaque lesion area. These effects suggest a direct role of leptin in modulating VLDL levels and, likewise, the lesion areas in VLDL-enriched animals. These two lines of mice represent new models with features of the metabolic syndrome and will be useful in testing therapies targeted for combating the human condition.
 ...
PMID:Generation and characterization of two novel mouse models exhibiting the phenotypes of the metabolic syndrome: Apob48-/-Lepob/ob mice devoid of ApoE or Ldlr. 1816 Apr 59

Obesity is an increasing health problem not only in the industrialized western countries but, also in the developing countries like India. The adipose tissue specific obese (ob) gene and its peptide product leptin were discovered in 1994. Leptin binding to specific receptors in the hypothalamus results in altered expression of orexigenic and anorexigenic neuropeptides that regulate neuroendocrine functions and energy homeostasis. Recent patents and experimental evidence suggest that leptin plays an important role in the pathogenesis of obesity and eating disorders. Central leptin action also includes regulation of blood pressure, bone mass, and immune function. Peripherally also, leptin plays an important role in direct regulation of immune cells, pancreatic beta cells, adipocytes and muscle cells. Leptin receptors are present on human endothelial cells, and it has been shown to induce angiogenesis both in vitro and in vivo. Further, leptin appears to be a potential pressure and volume regulating factor and may function pathophysiologically as a common link to obesity and hypertension. Obesity is also a risk factor for several other cardiovascular diseases like myocardial hypertrophy, myocardial infarction, coronary atherosclerosis and increased cardiovascular morbidity and mortality. Recent progress in understanding central and peripheral leptin receptor signaling pathways may provide potential new targets to combat obesity, hypertension etc.
 ...
PMID:Leptin and the cardiovascular system: a review. 1822 Nov 8

Obesity results from an abnormal accumulation of fat in the white adipose tissue. Recent research utilizing genetic models of obesity in rodents has implicated a major role of leptin as a controller of obesity. Leptin is a 167-amino acid peptide hormone encoded by the obesity gene (ob), which is secreted by adipocytes and plays an important role in regulating food intake, energy expenditure and adiposity. Leptin receptors (OB-R) are expressed in the central nervous system mainly in afferent satiety centres of hypothalamus and in peripheral organs such as adipose tissues, skeletal muscles, pancreatic beta-cells and liver, thus indicating the autocrine and paracrine role of leptin in energy regulation. In human beings, a highly organized circadian pattern of leptin secretion is observed with peak levels in the midnight probably resulting from cumulative hyperinsulinemia of entire day. Leptin has a dual role in weight maintenance. Leptin reflects total body adipose tissue mass whereas in conditions of negative and positive energy balance, the dynamic changes in plasma leptin concentration function as a sensor of energy balance and influence the efferent energy regulation pathways. Many effects of leptin on metabolism are mediated by interaction with Insulin and also by synergistic action with cholecystokinin. Besides physiological roles, leptin may influence pathological conditions like obesity-associated atherosclerosis, oxidative stress and cancers. The purpose of the present review is to summarize the important aspects of the biology, actions, and regulation of leptin and to serve as an update of new information.
 ...
PMID:Leptin and its metabolic interactions: an update. 1828 36


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>