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

Both ectopic fat accumulation and changes of the amount of several adipocyte secreting proteins (adipokines) are thought to contribute to the development of insulin resistance associated with obesity and type 2 diabetes mellitus. We have now investigated the effects of 2 insulin-sensitizing drugs, pioglitazone and metformin, on body fat composition and serum adipokine concentrations in individuals with type 2 diabetes mellitus. A total of 41 diabetic patients were treated with pioglitazone (n =21) or metformin (n =20) for 6 months. Intramyocellular lipid content (IMCL) and hepatic lipid content as well as the areas of subcutaneous and visceral fat deposits in the abdomen were determined by nuclear magnetic resonance spectroscopy before and after drug treatment. The serum concentrations of adiponectin and retinol binding protein 4 were also determined by enzyme-linked immunosorbent assays. Pioglitazone treatment reduced both hepatic lipid content (12.0 +/- 6.1 vs 8.4 +/- 3.7 arbitrary units [AU], P < .01) and IMCL (8.4 +/- 3.6 vs 6.3 +/- 2.4 AU/creatine, P < .01), whereas metformin reduced only IMCL (7.0 +/- 3.6 vs 5.8 +/- 2.0 AU/creatine, P < .05). Although the areas of visceral and subcutaneous fat were not significantly affected by treatment with either drug, pioglitazone induced a significant reduction in the ratio of visceral to subcutaneous fat area (0.92 +/- 0.41 vs 0.85 +/- 0.41, P < .05). Pioglitazone treatment also resulted in a marked increase in serum adiponectin concentration (5.6 +/- 4.1 vs 16.2 +/- 9.9 microg/mL, P < .0001) and a small but significant decrease in serum retinol binding protein 4 concentration (73.4 +/- 25.1 vs 65.1 +/- 23.7 microg/mL, P < .05). These results suggest that pioglitazone may improve insulin sensitivity both by affecting serum adipokine concentrations and by reducing the intracellular triglyceride content of liver and skeletal muscle in individuals with type 2 diabetes mellitus.
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PMID:Effects of pioglitazone and metformin on intracellular lipid content in liver and skeletal muscle of individuals with type 2 diabetes mellitus. 1788 55

Even though visfatin has been suggested as a proinflammatory adipokine, there are few studies of the relationship between plasma visfatin concentrations and proinflammatory markers in the nondiabetic population. We showed that plasma visfatin concentrations were positively associated with circulating interleukin-6 levels and diastolic blood pressure independent of obesity in nondiabetic healthy Korean women. These results suggest that circulating visfatin may be related with some proinflammatory condition even in a nondiabetic state.
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PMID:Plasma visfatin levels are positively associated with circulating interleukin-6 in apparently healthy Korean women. 1790 42

Obese mice that lack leptin receptor (db (-) /db (-)) have been shown to have innate bronchial hyperresponsiveness (BHR). It has been proposed that the obesity-mediated BHR may involve a combination of increased leptin and reduced systemic adiponectin levels. The aim of this study was to determine if obesity modifies the airway concentration of leptin and adiponectin and whether treatment with a synthetic peroxisome proliferator-activated receptor gamma (PPARgamma) ligand can reduce airway leptin and increase airway adiponectin. In this study, obese, leptin receptor-deficient (db (-) /db (-)), or lean (db ( + ) /db (-)) mice were treated with rosiglitazone (3 mg/kg/day) or vehicle by gavage daily for 1 week. Bronchioalveolar lavage (BAL) was subsequently performed to determine levels of leptin, adiponectin, and inflammatory cytokines. Treatment with rosiglitazone increased BAL adiponectin levels in lean (p = 0.04) and to a lesser extent in obese mice (p = 0.07). Rosiglitazone treatment lowered leptin levels in lean mice, but increased leptin levels in BAL fluid of obese mice (p < 0.01). The BAL levels of granulocyte-macrophage colony-stimulating factor (GM-CSF) were lower in the lean rosiglitazone-treated group compared with the obese vehicle-treated group and lower in the obese rosiglitazone-treated group compared with the obese vehicle-treated group. These results demonstrate that obesity is associated with alterations in adipokine and cytokine levels in the airways that can be modulated by treatment with roziglitazone.
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PMID:The peroxisome proliferator activated receptor gamma (PPARgamma) ligand rosiglitazone modulates bronchoalveolar lavage levels of leptin, adiponectin, and inflammatory cytokines in lean and obese mice. 1790 95

The objective of this study was to review the available information on the signaling proteins produced by adipose tissue in the context of their role in regulating reproductive processes, including ovarian and uterine function. It is well known that both obesity and excessive leanness are associated with reproductive dysfunction. Adipokines are cytokines predominantely or exclusively expressed by adipose tissue that circulate and affect target tissues. Four known adipokines, adiponectin, visfatin/PBEF, omentin and vaspin, all increase tissue sensitivity to insulin, and are thus described as 'beneficial'. There is strong support for a role for adiponectin in the function of the ovary and placenta. There is evidence for direct effects of this adipokine on the late stages of folliculogenesis, and additive interactions of adiponectin with insulin and gonadotropins in inducing periovulatory changes in ovarian follicles. In addition, clinical and genomic studies associate hypoadiponectinemia with obesity-related reproductive disorders, including the polycystic ovarian syndrome. The roles for visfatin/PBEF, omentin and vaspin in reproduction remain to be established. The conclusion thus drawn is that the expression of insulin-sensitizing adipokines varies with adipose abundance. These adipokines have demonstrated both the potential effects on ovarian function and the possible effects on the formation of the placenta, acting through multiple mechanisms.
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PMID:The 'beneficial' adipokines in reproduction and fertility. 1792 61

Obesity is a major global health problem and is associated with low-grade inflammation and, in a number of cases, poor iron status. We speculated that the adipokine leptin might play a role in regulating iron metabolism in the overweight population because it shares a number of common biological features with IL-6, a major factor in the development of the anemia of chronic disease via its stimulatory actions on the production and release of the iron regulatory hormone hepcidin. To test this hypothesis, we exposed HuH7 human hepatoma cells to leptin and measured hepcidin mRNA expression by quantitative PCR. HuH7 cells were also transfected with a hepcidin promoter-luciferase reporter gene construct to investigate transcriptional regulation of hepcidin. In leptin-treated cells, hepcidin mRNA expression was enhanced significantly. Preincubation with a Janus kinase (JAK) 2 inhibitor significantly diminished this response. Hepcidin promoter activity was also increased in the presence of leptin. This effect was decreased either by mutation of the signal transducer and activator of transcription (STAT) 3 binding motif in the hepcidin promoter or by coexpressing a dominant-negative STAT3 mutant. These data suggest that leptin upregulates hepatic hepcidin expression through the JAK2/STAT3 signaling pathway. As a consequence, the increased production of leptin in overweight individuals might be a major contributor to the aberrant iron status observed in these population groups.
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PMID:Leptin increases the expression of the iron regulatory hormone hepcidin in HuH7 human hepatoma cells. 1795 71

Visfatin, is a new adipokine, highly expressed in the visceral fat of both mice and humans. To examine whether visfatin is expressed in human peripheral monocyte-enriched mononuclear cells and whether its expression is altered in type 2 diabetes (DM2), we compared 24 DM2 women [17 overweight (BMI >25) and 7 lean (BMI<25)] to 26 healthy women (14 overweight and 12 lean), all premenopausal. Relative visfatin mRNA levels were significantly higher (approximately 3-fold) in DM2 compared to healthy control women (p<0.02), independently of the presence of overweight/obesity. Mononuclear TNF-alpha and IL-6 mRNA expression was also elevated in DM2 compared to control women (p=0.001 and p=0.004, respectively), an increase observed in both lean and overweight DM2 women. By contrast, circulating visfatin, TNF-alpha, and IL-6 levels showed no difference between DM2 and control women, while adiponectin plasma levels were significantly decreased in the DM2 women (p<0.001). Circulating visfatin and TNF-alpha levels did not differ either between the lean and the overweight subgroups of DM2 and control women, while IL-6 plasma levels were significantly higher in both overweight subgroups compared to their lean counterparts. In conclusion, visfatin, TNF-alpha, and IL-6 mRNA expressions are increased in peripheral mononuclear-monocytic cells from women with type 2 diabetes, independent of their BMI, which may enhance the effects of their adipose-derived levels and may contribute to the increased insulin resistance and atherogenic risk of these patients.
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PMID:Visfatin, TNF-alpha and IL-6 mRNA expression is increased in mononuclear cells from type 2 diabetic women. 1795 40

Interleukin-6 (IL-6) is a central player in the regulation of inflammation, haematopoiesis, immune response and host defense mechanisms. During the last decade, an accumulating amount of data suggested a pivotal role for IL-6 in metabolic processes, thus fortifying the picture of IL-6 as a multifaceted, pleiotropic cytokine. Because of its secretion by adipose tissue and contracting skeletal muscle and its broad action on central and peripheral organs, IL-6 has been termed an adipokine and a myokine. Its quantitative release from adipose tissue results in a subclinical, systemic elevation of IL-6 plasma levels with increasing body fat content, which may be implicated in the proinflammatory state leading to insulin resistance. On the other hand, IL-6 produced in the working muscle during physical activity could act as an energy sensor by activating AMP-activated kinase and enhancing glucose disposal, lipolysis and fat oxidation. In addition, both impaired IL-6 secretion and action are risk factors for weight gain. Thus, IL-6 clearly has lipolytic effects and anti-obesity potential. However, the application of IL-6 itself is at least limited by a narrow therapeutic range and its important function for a balanced inflammatory response. Further studies on the molecular basis of the metabolic effects of IL-6 could elucidate novel therapeutic strategies for custom-designed, IL-6-related substances.
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PMID:The role of interleukin-6 in insulin resistance, body fat distribution and energy balance. 1795 45

Migration and hibernation in mammals may be preceded by a period of leptin resistance, which may in part account for the increasing adiposity and body mass that occurs during these periods. We hypothesized that hypothalamic expression of leptin receptor mRNA would decrease during the premigration (PM) period in the little brown myotis, Myotis lucifugus. Body mass of M. lucifugus increased during the PM period, but serum leptin levels did not change during that time. Hypothalamic mRNA levels for both the short (ObRa) and fully active long (ObRb) forms of the leptin receptor increased during PM, but the relative increase in ObRa was larger and occurred sooner than ObRb. mRNA levels of an inhibitor of leptin signaling (protein inhibitor of activated STAT3: PIAS3) increased in hypothalami during the PM period in bats. Adiponectin is an adipokine that has been linked to obesity in rodents; normally, serum levels of adiponectin decrease in obesity. In M. lucifugus, adiponectin mRNA levels decreased in adipose tissue during the period of mass gain, but circulating adiponectin levels did not change. We conclude that the relative changes in leptin receptor isoform expression during the PM fattening period may favor binding of leptin to the less active short isoform. Coupled with increased expression of PIAS3 and the dissociation of serum leptin levels from body mass and adiposity, these changes could account in part for the adaptive fattening during the PM period. In addition, the adipokine profiles of M. lucifugus during the PM period and that of obesity in non-hibernating mammals are strikingly dissimilar.
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PMID:Changes in body mass, serum leptin, and mRNA levels of leptin receptor isoforms during the premigratory period in Myotis lucifugus. 1796 52

Tumor necrosis factor-alpha (TNF-alpha) is chronically elevated in adipose tissues of obese rodents and humans. Increased levels of TNF-alpha are implicated in the induction of atherogenic adipokines, such as plasminogen activator inhibitor -1 (PAI-1) and IL-6, and the inhibition of the anti-atherogenic adipokine, adiponectin. In this study, we investigated the effects of resveratrol on TNF-alpha-induced atherogenic changes of the adipokines in 3T3-L1 cells. Exposure to TNF-alpha for 24 h increased PAI-1 and IL-6 secretion and decreased adiponectin secretion. The mRNA expression of adipokines changed in parallel with mRNA expression. Resveratrol effectively reversed the secretion and mRNA expression of the atherogenic adipokines, PAI-1 and IL-6, induced by TNF-alpha. Decreased secretion levels and mRNA expression of adiponectin by TNF-alpha were also recovered by resveratrol treatment. Our results suggest that resveratrol may improve obesity-induced cardiovascular disease, particularly atherosclerosis, by attenuating the TNF-alpha-induced changes of adipokines.
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PMID:Resveratrol inhibits TNF-alpha-induced changes of adipokines in 3T3-L1 adipocytes. 1796 14

Type 2 diabetes is widespread and its prevalence is increasing rapidly. In the US alone, approximately 41 million individuals have prediabetes, placing them at high risk for the development of diabetes. The pathogenesis of type 2 diabetes involves inadequate insulin secretion and resistance to the action of insulin. Suggestive data link insulin resistance and accompanying hyperglycemia to an excess of abdominal adipose tissue, a link that appears to be mediated partially by adipocyte secretion of multiple adipokines that mediate inflammation, thrombosis, atherogenesis, hypertension, and insulin resistance. The adipokine adiponectin has reduced expression in obesity and appears to be protective against the development of type 2 diabetes. Current recommendations to prevent type 2 diabetes center on lifestyle modifications, such as diet and exercise. Clinical trials have established the efficacy of lifestyle intervention, as well as pharmacologic interventions that target glycemic control or fat metabolism. However, diabetes did develop in a substantial percentage of individuals who received intensive intervention in these trials. Thus there is an unmet need for additional strategies in high-risk individuals. Recent data suggest thiazolidinediones and blockade of the endocannabinoid system represent novel therapeutic approaches that may be used for the prevention of diabetes.
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PMID:The burden of type 2 diabetes: strategies to prevent or delay onset. 1796 81


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