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Query: UMLS:C0020538 (hypertension)
 170,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Resistin, the peptide specifically secreted from adipocytes, is a hormone antagonistic to insulin action and, thus, may serve as a link between human obesity due to adiposity and insulin resistance associated with type 2 diabetes. To test this hypothesis, we studied the gene expression of resistin in adipocytes isolated from rats fed with a fructose diet which induced insulin resistance. Compared to the control rats (C) on a normal chow diet, the fructose-fed rats (F) developed hyperinsulinemia, glucose intolerance, hypertriglyceridemia and hypertension, a profile reminiscent of the syndrome X of patients with non-insulin-dependent diabetes mellitus (NIDDM). The F rats had significantly elevated plasma free fatty acids (FFA), enlarged epididymal fat pads, and increased adipocyte size compared with the C rats. We examined the glucose transport and the relative quantity of resistin mRNA produced in the adipocytes of these two groups of rats. Compared to the C rats, the F rats had a clearly reduced insulin-stimulated glucose transport. The gene expression of resistin and other adipocyte peptides was measured on the mRNA by semiquantitative RT-PCR; the validity of this technique was established in advance with a rat-fasting and then refeeding experiment. The F rats showed a decreased expression of the resistin gene, whereas gene expression of leptin and angiotensinogen in contrast increased. Free fatty acids were found to suppress the expression of resistin gene in normal rat adipocytes. These results demonstrate that an insulin-resistant instance in the fructose diet rat model exists with the decreased gene expression of resistin.
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PMID:Suppressed gene expression of adipocyte resistin in an insulin-resistant rat model probably by elevated free fatty acids. 1174 41

Leptin regulates cardiovascular function. Leptin levels are elevated in obesity and hypertension and may play a role in cardiovascular dysfunctions in these comorbidities. This study was designed to determine the influence of hypertension on the cardiac contractile response of leptin. Mechanical and intracellular Ca(2+) properties were evaluated using an IonOptix system in ventricular myocytes from spontaneously hypertensive (SHR) and age-matched Wistar Kyoto (WKY) rats. The contractile properties included peak shortening (PS), duration and maximal velocity of shortening/relengthening (TPS/TR(90), +/-dL/dt), and fura-fluorescence intensity change (DeltaFFI). NO and nitric oxide synthase (NOS) activity were assessed by the Griess and the (3)H-arginine/citrulline conversion assays, respectively. The leptin receptor (Ob-R) and the Janus kinase/signal transducer and activator of transcription (JAK/STAT) signaling pathway were evaluated by Western blot analysis. SHR animals displayed significantly elevated blood pressure and plasma leptin levels. Leptin elicited a concentration-dependent inhibition of PS and DeltaFFI in WKY, but not in SHR myocytes. Leptin did not affect TPS, TR(90), or +/- dL/dt. The difference in leptin-induced contractile response between the WKY and the SHR groups was abolished by the NOS inhibitor, Nomega-nitro-L-arginine methyl ester (L-NAME), but not by elevated extracellular Ca(2+). Either the JAK2 inhibitor AG-490 or the mitogen-activated protein (MAP) kinase inhibitor SB203580 abrogated the leptin-induced response in the WKY myocytes, whereas AG-490 unmasked a negative response in PS in the SHR myocytes. SHR myocytes displayed similar Ob-R protein abundance and basal NO levels, a blunted leptin-induced increase in NOS activity as well as enhanced basal STAT3 levels compared with the WKY group. These data indicate that the leptin-induced cardiac contractile response is abolished by spontaneous hypertension, possibly because of mechanisms involving altered JAK/STAT, MAP kinase signaling, and NO response.
Hypertension 2002 Jan
PMID:Abrogated leptin-induced cardiac contractile response in ventricular myocytes under spontaneous hypertension: role of Jak/STAT pathway. 1179 81

This study was conducted to evaluate the relative contributions of existing obesity and a family history of obesity (FHOB) to blood pressure (BP) level, sympathetic activity, plasma leptin and insulin levels in young men without a family history of hypertension. The study was of "four-corner" design according to body mass index (BMI). A positive FHOB (FHOB+) was defined as both parents being obese (BMI >26.0 kg/m2), and a negative FHOB (FHOB-) was defined as both parents being lean (BMI <22.0 kg/ m2). The cutoff limits of BP for the subjects and their parents enrolled in present study was defined as a supine reading of <140/90 mmHg. In 12 lean young subjects with FHOB-, 9 obese young subjects with FHOB-, 8 lean young subjects with FHOB+ and 16 obese young subjects with FHOB+, BMI, BP, plasma norepinephrine (NE), insulin and leptin were measured. All subjects were men and non-diabetic. Obese subjects, irrespective of FHOB, had higher levels of BMI, BP, plasma NE, leptin and insulin compared to lean subjects. In subjects with FHOB+, regardless of their current degree of adiposity, there was a higher level of BP and plasma NE than in subjects with FHOB-. In lean subjects, FHOB+ was associated with a higher plasma NE level and BP, but similar levels of plasma leptin and insulin were found when compared with FHOB- subjects. These results suggest that existing obesity and a positive family history of obesity appear to have an association with sympathetic overactivity and BP elevation.
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PMID:Familial obesity, sympathetic activation and blood pressure level. 1180 57

Leptin, a hormone secreted by adipose tissue, acts to inhibit appetite and promote metabolism, thereby reducing body weight. Leptin also increases sympathetic activity and arterial pressure. Several murine models of obesity, including agouti obese mice, exhibit resistance to the anorexic and weight-reducing effects of leptin. Hypertension in agouti mice has been attributed to hyperleptinemia. These observations pose a seeming paradox. If these mice are leptin-resistant, then how can leptin contribute to hypertension? We tested the novel hypothesis that these mice have selective leptin resistance, with preservation of the sympathoexcitatory action despite resistance to the weight-reducing actions. Leptin-induced decreases in food intake and body weight were less in agouti obese mice than in lean littermates. In contrast, leptin-induced increases in sympathetic nerve activity did not differ in obese and lean mice. These findings support the concept of selective leptin resistance, with resistance to the metabolic actions of leptin but preservation of the sympathoexcitatory actions. This finding may have potential implications for human obesity, which is associated with elevated plasma leptin and is thought to be a leptin-resistant state. If leptin resistance is selective in obese humans, then leptin could contribute to sympathetic overactivity and its adverse consequences in human obesity.
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PMID:The concept of selective leptin resistance: evidence from agouti yellow obese mice. 1181 52

Obesity is a major health problem that contributes to the development of type 2 diabetes, hypertension, dyslipidemia, and cardiovascular disease. The current pharmacological therapies for obesity are limited and may have significant side effects. Leptin therapy was shown to effectively cause weight loss in obese rats, however its effectiveness in humans is still under investigation. Obese humans have significantly elevated plasma leptin concentrations compared with lean individuals. Plasma leptin concentrations strongly correlated with percentage of body fat. Leptin concentration in the cerebrospinal fluid (CSF) is correlated, in a nonlinear manner, with plasma leptin levels and body mass index (BMI). The ratio of CSF leptin levels to serum leptin levels was 4 times greater in lean individuals than in obese individuals. One interpretation of this finding is that human obesity could be secondary to a central resistance to leptin action, causing a relative leptin deficiency in the CNS. Six years after the discovery of leptin we still do not have a clear understanding of how leptin accesses its targets in the brain, or whether there is defect in this process in the brain of obese individuals. In this manuscript we will review the different leptin gateways to the brain and the potential sites where a defect in leptin action may be present, as well as some potential clinical implications of leptin. A better understanding of how leptin reaches the brain and how it modulates the release of hypothalamic neuropeptides will be important in understanding the role that leptin plays in the pathophysiology of obesity.
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PMID:Limited brain access for leptin in obesity. 1182 2

The industrialized countries around the world are experiencing an epidemic of childhood obesity. The level of fatness of a child at which morbidity increases acutely and/or later in life is determined on an individual basis. Overall, however, childhood obesity substantially increases the risk of subsequent morbidity whether or not obesity persists into adulthood. The genetic basis of childhood obesity has been elucidated to some extent through the discovery of leptin, the ob gene product, and the increasing knowledge of the role of neuropeptides such as pro-opiomelanocortin, neuropeptide Y and the melanocyte-concentrating hormone receptors. Environmental and exogenous factors are the main contributors to the development of a high degree of body fatness early in life. Studies involving twins suggest that approximately 50% of the tendency toward obesity is inherited. There are numerous disorders, including a number of endocrine disorders, such as Cushing's syndrome and hypothyroidism, and genetic syndromes, such as Prader-Labhard-Willi syndrome and Bardet-Biedl syndrome, that can present with obesity. A simple diagnostic algorithm allows for differentiation between primary and secondary obesity. Among the most common sequelae of primary childhood obesity are hypertension, dyslipidemia, back pain and psychosocial problems. It is somewhat ironic that the definition of obesity in childhood is not an easy one. Direct measurements of body fat content, such as hydrodensitometry, bioimpedance, or dual-energy X-ray absorptiometry, are useful tools in scientific studies. Body mass index (BMI) is, however, now generally accepted to be a good clinical measure for the definition of obesity in children and adolescents. In preadolescent boys, BMI also relates to muscle mass and should be used for the definition of fat mass with great caution. An increased risk of death from cardiovascular disease in adults has been found in patients whose BMI had been greater than the 75th percentile as adolescents. Therapeutic strategies include psychological and family therapy, modification of lifestyle and behavior, and nutritional education. The role of regular exercise and exercise programs is emphasized, while surgical procedures and drugs used in adult obesity are still not generally recommended for obese children. Obesity is the most common chronic disorder in industrialized countries, and its impact on individual lives as well as on health economics must be recognized by physicians and the public alike. This review aims to increase awareness of the health burden and economic dimension of the epidemic of childhood obesity that is occurring around the globe.
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PMID:Obesity in childhood and adolescence: clinical diagnosis and management. 1183 96

Metabolic Syndrome X is a cluster of abnormalities including insulin resistance, hyperlipidemia, hypertension, and obesity. We sought to determine if excess plasma glucagon and free fatty acids (FFA) might contribute to the insulin resistance in the obese spontaneous hypertensive rat (SHROB), a unique animal model of leptin resistance and metabolic Syndrome X. SHROB were extremely hyperinsulinemic and mildly glucose intolerant compared with lean SHR. SHROB had elevated fasting plasma glucagon and FFA, and showed paradoxical responses to an oral glucose challenge, with increased glucagon at 30 and 60 min postchallenge (200% plus minus 45% and 91% plus minus 13%, respectively; n = 9). In lean SHR, glucagon was nearly unchanged by glucose loading (<30% increase, P > 0.05; n = 5). Plasma FFA were not affected by a glucose load in SHROB, whereas SHR showed a decrease of 40% plus minus 6% (n = 5--9). The I/G molar ratio changed in opposite directions in the two genotypes, with a decrease in SHROB at 30 and 60 min, in contrast to the appropriate increase at 30 and 60 min postchallenge in the lean SHR (P < 0.01; n = 5--9). Administration of 500 ng/kg exogenous glucagon to SHR raised glucagon 56% plus minus 5% to a level that was similar to fasting SHROB. This level of circulating glucagon was sufficient to elevate glucose and insulin during the 7 hr of observation (n = 9). Based on these results, we suggest that fasting hyperglucagonemia and impaired suppression of glucagon secretion and FFA in response to an oral glucose load may contribute to insulin resistance and glucose intolerance in the SHROB model of metabolic Syndrome X.
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PMID:Plasma glucagon and free fatty acid responses to a glucose load in the obese spontaneous hypertensive rat (SHROB) model of metabolic syndrome X. 1185 14

Obesity is a multifactorial disease that arises from complex interactions between genetic predisposition and environmental factors. It increases a risk of cardiovascular and metabolic diseases such as diabetes, hypertension, and hyperlipidemia. Recent molecular genetic studies have disclosed some monogenic forms of obesity in humans. Leptin directly exerts its anorexigenic effects on hypothalamic arcuate nucleus. alpha-melanocyte stimulating hormone (alpha-MSH) derived from proopiomelanocortin (POMC) and melanocortin-4 receptor (MC4-R) have been reported to be involved in the downstream of leptin actions. In this paper, we summarize the clinical characteristics and the mechanisms of obesity caused by genetic abnormalities in leptin receptor and melanocortin-4 receptor.
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PMID:[Obesity induced by abnormality in leptin receptor and melanocortin-4 receptor]. 1185 34

Although the pathogenesis of the obesity-related hypertension is not fully understood, prevalence of the cardiovascular complications is much higher in obese men than obese women. In a recent study, we reported that male rats fed a cafeteria diet, while becoming obese, developed hypertension and important changes in their renal alpha2-adrenergic receptor subtypes distributions. The aim of the present study was to investigate whether these alterations are sex dependent. After 10 weeks of the cafeteria diet, male and female rats had the same increase in fat pad weight and in plasma leptin levels. However, in contrast to males, females had normal blood pressure (BP). On the basis of radioligand-binding studies using [3H]-RX821002 and confirming our recent observation, an increase in alpha2-adrenergic receptor densities occurred in kidneys of cafeteria-fed male but not female rats. Moreover, in contrast with the situation observed in males, ligand competition studies failed to reveal any change in the renal alpha2A- and alpha2B-adrenergic receptors subtypes distribution in females. Finally, in the cafeteria-fed females reverse transcription-polymerase chain reaction experiments showed unaltered expression of these two alpha2-adrenergic receptor subtypes. These data thus suggest a strong relationship between the sexual dimorphism in the cafeteria diet-induced hypertension and altered expression of the alpha2-adrenergic receptor subtypes in the kidney.
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PMID:Gender difference in diet-induced obesity hypertension: implication of renal alpha2-adrenergic receptors. 1186 49

Leptin is a major adipocyte-derived hormone that is involved in the regulation of food intake and energy expenditure. Plasma leptin concentrations are elevated in obese subjects, suggesting its pathophysiological role in obesity-related lifestyle-related diseases. We have recently succeeded in the generation of transgenic skinny mice overexpressing leptin. They exhibit increased glucose metabolism and insulin sensitivity accompanied by a significant increase in insulin signaling for glucose utilization in the skeletal muscle and liver. They also show blood pressure elevation through the sympathetic activation. Introduction of the lethal yellow agouti (A(y)) allele into transgenic skinny mice results in late-onset obesity and diabetes with blood pressure elevation similar to those found in nontransgenic agouti mice (A(y)/+ mice). After caloric restriction, blood pressure elevation is reversed but insulin resistance still remains in A(y)/+ mice in parallel with a reduction of plasma leptin concentrations. By contrast, blood pressure elevation is sustained but insulin resistance is reversed in transgenic mice overexpressing leptin with the A(y) allele (Tg/+:A(y)/+ mice), which remain hyperleptinemic. Collectively, our data suggest the pathophysiologic and therapeutic implication of leptin in obesity-related insulin resistance and hypertension.
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PMID:Pathophysiogical role of leptin in lifestyle-related diseases. Studies with transgenic skinny mice overexpressing leptin. 1187 79


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