Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adipocytokines, fat tissue derived factors with regulatory properties, are involved in the pathophysiology of atheromatous and metabolic illnesses such as: ischemic heart disease, insulin resistance, obesity, dyslipidemia and diabetes mellitus. Enlargement of visceral adipose tissue depots determines a worse evolution for those complaints. Drugs as angiotensin converting enzyme inhibitors (ACEI), thiazolidinediones (glitazones) or angiotensin-II receptor antagonists, generally associated with the adequate hypolipidemic (statins, fibrates) or antiobesity (orlistat, sibutramine, rimonabant) medication, would increase those adipocytokines with anti-inflammatory and insulin-sensitizing properties (i.e. adiponectin or visfatin), while reducing pro-inflammatory and thrombogenic cytokines (as leptin, tumor necrosis factor [TNF]-alpha, plasminogen activator inhibitor 1 [PAI-1]). Thus, these pharmacologic therapeutic approaches would have a beneficial effect in order to diminish morbidity-mortality and improve the prognosis of patients with said diseases, all of them related to high cardiovascular risk.
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PMID:[Adipocytokines: implications in the prognosis and drug treatment of cardiovascular diseases]. 1845 36

Psoriasis is a chronic immune-inflammatory-mediated disease that can predispose patients to other inflammatory conditions. For example, individuals with psoriasis are at increased risk for insulin resistance, obesity, dyslipidemia, and hypertension--components that characterize the metabolic syndrome. The metabolic syndrome is an important driver of adverse cardiovascular outcomes. Proinflammatory cytokines, such as tumor necrosis factor-alpha (TNF-alpha), and other factors that are overproduced in patients with psoriasis likely contribute to the increased risk for development of metabolic syndrome. This article reviews the association of psoriasis with metabolic syndrome, as well as the impact of biologic agents that are currently used to treat psoriasis (ie, TNF antagonists) on risk factors for metabolic syndrome.
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PMID:Psoriasis and the metabolic syndrome. 1856 88

Obesity with insulin resistance and alcohol are the most frequent causes of steatohepatitis. This work investigates the contribution of bioactive TNF and Th1 type cytokines in a mouse model of steatohepatitis induced by FAT alone or FAT+EtOH and endotoxin. The extent of liver injury and cytokine activation induced by endotoxin in chronic FAT-fed mice, FAT+EtOH-fed mice, or mice fed standard chow were analyzed. Endotoxin administration to either FAT-fed or FAT+EtOH-fed mice increased serum ALT and AST compared to standard chow mice. Immunoreactive TNF was strongly activated by LPS in FAT-fed and FAT+EtOH-fed mice which presented the highest levels, but low levels were found in standard chow mice. In contrast, bioactive TNF was only present in serum of FAT-fed and in particular the highest levels were found in FAT+EtOH-fed mice. Moreover, soluble TNFR2 but not TNFR1 was found in lower amounts in serum of FAT+EtOH-fed mice compared to FAT-fed mice. Steatohepatitis was associated with increased IL-6, IFN-gamma, and iNOS mRNA and proteins. Data show that a moderately FAT diet and low-dose EtOH concur to generate steatohepatitis and TNF liver expression after LPS. In this model, changes in the regulation of TNF are associated with increased expression of IL-6, IFN-gamma, and iNOS.
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PMID:Fat diet and alcohol-induced steatohepatitis after LPS challenge in mice: role of bioactive TNF and Th1 type cytokines. 1872 87

Adiposity and adipocyte-derived cytokines have been implicated in prostate carcinogenesis. However, the relationship of adipokine gene variants with prostate cancer risk has not been thoroughly investigated. We therefore examined common variants of the IL6, LEP, LEPR, TNF and ADIPOQ genes in relation to prostate cancer in a case-control study nested within a large cohort of Finnish men. The study sample consisted of 1,053 cases of prostate cancer, diagnosed over an average 11 years of follow up, and 1,053 controls matched to the cases on age, intervention group and date of baseline blood draw. Logistic regression was used to model the relative odds of prostate cancer. We also examined genotypes in relation to serum insulin, IGF-1 and IGF-1:IGFBP-3 among 196 controls. Variant alleles at three loci (-14858A>G, -13973A>C, -13736C>A) in a potential regulatory region of the LEP gene conferred a statistically significant 20% reduced risk of prostate cancer. For example, at the -14858A>G locus, heterozygotes and homozygotes for the A allele had an odds ratio (OR) of prostate cancer of 0.76 [95% confidence interval (CI) 0.62, 0.93] and 0.79 (95% CI 0.60, 1.04), respectively. At 13288G>A, relative to the GG genotype, the AA genotype was associated with a suggestive increased risk of prostate cancer (OR = 1.29; 95% CI 0.99,1.67; p(trend) = 0.05). Polymorphisms in the IL6, LEPR, TNF and ADIPOQ genes were not associated with prostate cancer. Allelic variants in the LEP gene are related to prostate cancer risk, supporting a role for leptin in prostate carcinogenesis.
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PMID:Adipokine genes and prostate cancer risk. 1903 56

Hepatic steatosis and liver degeneration are prominent features of the zebrafish ducttrip (dtp) mutant phenotype. Positional cloning identified a causative mutation in the gene encoding S-adenosylhomocysteine hydrolase (Ahcy). Reduced Ahcy activity in dtp mutants led to elevated levels of S-adenosylhomocysteine (SAH) and, to a lesser degree, of its metabolic precursor S-adenosylmethionine (SAM). Elevated SAH in dtp larvae was associated with mitochondrial defects and increased expression of tnfa and pparg, an ortholog of the mammalian lipogenic gene. Antisense knockdown of tnfa rescued hepatic steatosis and liver degeneration in dtp larvae, whereas the overexpression of tnfa and the hepatic phenotype were unchanged in dtp larvae reared under germ-free conditions. These data identify an essential role for tnfa in the mutant phenotype and suggest a direct link between SAH-induced methylation defects and TNF expression in human liver disorders associated with elevated TNFalpha. Although heterozygous dtp larvae had no discernible phenotype, hepatic steatosis was present in heterozygous adult dtp fish and in wild-type adult fish treated with an Ahcy inhibitor. These data argue that AHCY polymorphisms and AHCY inhibitors, which have shown promise in treating autoimmunity and other disorders, may be a risk factor for steatosis, particularly in patients with diabetes, obesity and liver disorders such as hepatitis C infection. Supporting this idea, hepatic injury and steatosis have been noted in patients with recently discovered AHCY mutations.
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PMID:TNFalpha-dependent hepatic steatosis and liver degeneration caused by mutation of zebrafish S-adenosylhomocysteine hydrolase. 1920 49

Chronic hepatitis C and obesity inflict significant health and economic burdens on the world. Insulin resistance associated to obesity is the key factor in this disease, mainly because it has been related to fibrosis extension and non-response to antiviral therapy. The mechanism underlying this correlation is not fully explained yet. Leptin, adiponectin, TNF alfa, the hepatic expression of suppressor of cytokine signalling 3 (SOCS3), and hyperinsulinemia have been considered as heavily influencing fibrosis extension and nonresponsiveness to the IFN-alpha. The adipokines increased hepatic expression of SOCS3, and hyperinsulinemia has been proposed as heavily influencing non-responsiveness to the IFN-alpha and fibrosis extension by maintaining the hepatic stellate cells activated phenotype in patients with chronic hepatitis C and insulin resistance-related obesity. We shall review the mechanisms by which obesity-related insulin resistance may be associated with fibrosis extension and decreased efficacy of IFN-alpha based therapies in obese individuals with chronic hepatitis C and the therapeutic strategies that may increase the effectiveness of these therapies. Consequently, being aware of the role of obesity-related insulin resistance in chronic hepatitis C, it will be possible to elaborate new therapeutic strategies for chronic hepatitis C obese patients. Also, it will be possible to elaborate new criteria for the initiation of antiviral therapy by including parameters such as body weight, abdominal circumference, HOMA-IR, the dosage of adipokines in order to more accurately define the groups of patients with a higher risk of non-responsiveness to antiviral therapy, thus lowering long-term costs.
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PMID:Impact of host insulin resistance on fibrosis and response to interferon in chronic hepatitis C. 1928 81

B cell activation factor (BAFF) is a novel member of the TNF ligand superfamily, mainly produced by myeloid cells. BAFF has been shown to participate in B-cell survival and B- and T-cell maturation. BAFF expression in adipocytes has been recently demonstrated. In the current study, we verified that BAFF expression is increased during adipocyte differentiation. BAFF expression was augmented by TNF-alpha treatment and was decreased by rosiglitazone treatment. BAFF secretion in lean and in ob/ob mice sera were compared and smaller amount of BAFF was secreted in ob/ob mice. mRNA and protein expression were different between epididymal and visceral adipose tissue. BAFF expression was also increased in ob/ob mouse adipose tissue. We sought to identify known BAFF receptors (BAFF-R, BCMA, and TACI) in adipocytes, and determined that all three were present and upregulated during adipocyte differentiation. However, the expression of TACI was distinct from that of BAFF-R and BCMA under TNF-alpha and BAFF ligand treatment. BAFF-R and BCMA expression levels were upregulated under pro-inflammatory conditions, but TACI was reduced. Conversely, BAFF-R and BCMA expression levels were downregulated by rosiglitazone treatment, but TACI was increased. Taken together, our results suggest that BAFF may be a new adipokine, representing a link between obesity and inflammation.
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PMID:B cell activation factor (BAFF) is a novel adipokine that links obesity and inflammation. 1929 40

The aim of the present study was to investigate the relationship of plasma resistin levels with determinants of the metabolic syndrome (MetS) and anthropometric parameters in healthy Korean subjects. Plasma resistin levels were determined in 276 subjects. In subjects with MetS, the plasma resistin levels were not significantly increased compared to those without MetS (8.3+/-4.3 ng/mL vs. 8.5+/-3.6 ng/mL, respectively, P=0.84). In addition, the plasma resistin levels were not correlated with the body mass index, the waist circumference, homeostasis model assessment-insulin resistance (HOMA-IR), fasting plasma glucose or insulin levels. However, the plasma resistin levels were positively correlated with the abdominal subcutaneous fat (r=0.18, P<0.01) in all subjects and correlated with TNF alpha(r=-0.16, P<0.05) and hsCRP (r=0.15, P<0.05) in subjects without MetS but not with MetS. With multiple linear regression analysis, these linear associations remained to be significant. The results of this study show that plasma resistin levels in humans were not associated with markers of insulin resistance, obesity or other determinants of the MetS.
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PMID:Association of plasma levels of resistin with subcutaneous fat mass and markers of inflammation but not with metabolic determinants or insulin resistance. 1965 55

Hidradenitis suppurativa is a chronic disease characterized by recurrent, painful, deep-seated, rounded nodules and abscesses of apocrine gland-bearing skin. Subsequent suppuration, sinus tracts and hypertrophic scarring are its main features. Onset is usually after puberty, although it is most common during the third decade and may persist in old age. The disease tends to be chronic and may develop to subcutaneous extension leading to indurations, sinus, and fistula having a profound impact on the quality of life. The prevalence is 1% in several studies. Axillary and inguinal involvement is more common in females; peri-anal and buttocks localizations are prevalent in males. The exact aetiology remains unknown. The primary event is a follicular occlusion with secondary inflammation, infection and destruction of the pilo-sebaceo-apocrine apparatus and extension to the adjacent sub-cutaneous tissue. Infection is common. Smoking may be a triggering factor. Obesity aggravates the discomfort. Differential diagnostic includes Crohn's disease, nodular acne and furonculosis. The main complications are arthropathy, carcinoma. Treatment depends upon the stage of the disease. Early nodular lesions may be treated by antibiotics for acute stage; long-term antibiotics, zinc salts may be useful as maintenance treatment; anti-TNF drugs have been used in severe cases; systemic steroids, estrogens, anti-androgens, retinoids have been used as options with limited success. Surgical treatment includes incision with or without drainage for limited abscesses; limited excisions are used for locally recurring draining sinuses. Total wide excision and healing with secondary intention or flaps and grafts is the only curative procedure in case of advanced disease.
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PMID:Hidradenitis suppurativa. 1968 81

The epidemic of obesity and overweight leads to many diseases including cardiovascular disease. Having an influence on function and heart structure, obesity and overweight are in connection with coronary heart disease, heart failure and sudden heart death. Cardiomyopathy in obesity (adipositas cordis) appears due to accumulation of adipose tissue between the heart muscle fibers and degeneration of myocites. The degeneration of myocardial could be due to lipotoxicity of free fatty acids in adipose tissue. The left ventricle hypertrophy, diastolic dysfunction, increasing blood volume, ejection fraction lead to heart failure. Obesity is low inflammation state with increased adipocitokine production from truncal adipose tissue which causes endothelial dysfunction and insulin resistance. Adipocitokines include leptin, adiponectin, resistin, visfatin, RBP 4 (retinol binding protein), angiotenzinogen, TNF alpha (tumor necrosis factor), PAI 1 (plazminogen activator inhibitor), fatty acids, sex steroids and different growth factors. Adipocitokines act synergistically or competitively with insulin, that explaining their impact on insulin resistance. Inflammatory citokines from adipose tissue could have influence on blood vessels endothelial function without their increase in plasma concentrations.
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PMID:[Obesity and coronary heart disease: the mechanism of atherogenic impact]. 1970 15


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