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

To elucidate mechanisms of melanocortin action, we investigated the effects of a melanocortin receptor agonist (melanotetan II [MTII]) in lean C57BL/6J and obese (DIO, ob/ob, UCP1-DTA) mice. MTII administration (100 microg q.i.d. i.p.) for 24 h results in similar weight loss but a more pronounced decrease of food intake in DIO mice. After 4 and 8 days of MTII treatment, however, the reduction in both food intake and body weight is more pronounced in DIO mice than in lean mice. MTII administration for 24 h prevents food deprivation-induced alterations in hypothalamic neuropeptide Y (NPY) and liver adiponectin receptor 1 and adiponectin receptor 2 mRNA expression, but does not alter hypothalamic mRNA expression of melanocortin 4 receptor or adiponectin serum and mRNA expression levels. NPY and agouti gene-related protein (AgRP) mRNA expression after 8 days of MTII is increased to levels comparable to pair-fed mice. In summary, 1) MTII is an effective treatment for obesity and related metabolic defects in leptin-resistant (DIO, UCP1-DTA) and leptin-sensitive (ob/ob) mouse models of obesity; 2) the effects of MTII on food intake and body weight are more pronounced in DIO mice than in lean mice; 3) the tachyphylactic effect after prolonged MTII administration appears to be, at least in part, caused by a compensatory upregulation of NPY and AgRP mRNA levels, whereas decreasing leptin levels may play a very minor role in mediating tachyphylaxis; and 4) alterations in adiponectin receptor mRNA expression after fasting or MTII treatment may contribute to altered insulin sensitivity and needs to be studied further.
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PMID:Responsiveness to peripherally administered melanocortins in lean and obese mice. 1469 1

The fat-derived protein adiponectin is an important insulin-sensitizing adipocytokine which is downregulated in insulin resistance and obesity. Recently, two receptors of this adipose-expressed protein called adiponectin receptor 1 (AdipoR1) and 2 (AdipoR2) have been cloned. To clarify expression and regulation of these receptors in fat cells, AdipoR1 and AdipoR2 mRNA was measured by quantitative real-time reverse transcription-polymerase chain reaction during differentiation of 3T3-L1 adipocytes and after treatment with various hormones known to induce insulin resistance. Interestingly, AdipoR2 synthesis was significantly increased up to 4.8-fold during differentiation of 3T3-L1 preadipocytes, whereas AdipoR1 expression was only augmented up to 1.4-fold. Furthermore, growth hormone (GH) induced AdipoR2, but not AdipoR1 mRNA by up to 2.4-fold in a dose- and time-dependent fashion with significant stimulation detectable at concentrations as low as 5 ng/ml GH and as early as 2 h after effector addition. The positive effect of GH on AdipoR2 expression could be reversed by withdrawal of the hormone for 24 h. In contrast, other key hormones involved in the regulation of insulin resistance and energy metabolism such as insulin, isoproterenol, dexamethasone, triiodothyronine, angiotensin 2, tumor necrosis factor alpha, and interleukin-6 did not influence AdipoR1 and AdipoR2 synthesis in vitro. Taken together, our results suggest that AdipoR2 expression is differentiation-dependent and selectively regulated by GH implying a potential role of this hormone in adiponectin-associated alterations of insulin sensitivity and energy homeostasis.
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PMID:Growth hormone is a positive regulator of adiponectin receptor 2 in 3T3-L1 adipocytes. 1475 11

Adiponectin is a hormone secreted from adipose tissue, and serum levels are decreased with obesity and insulin resistance. Because prolactin (PRL) and growth hormone (GH) can affect insulin sensitivity, we investigated the effects of these hormones on the regulation of adiponectin in human adipose tissue in vitro and in rodents in vivo. Adiponectin secretion was significantly suppressed by PRL and GH in in vitro cultured human adipose tissue. Furthermore, PRL increased adiponectin receptor 1 (AdipoR1) mRNA expression and GH decreased AdipoR2 expression in the cultured human adipose tissue. In transgenic mice expressing GH, and female mice expressing PRL, serum levels of adiponectin were decreased. In contrast, GH receptor deficient mice had elevated adiponectin levels, while PRL receptor deficient mice were unaffected. In conclusion, we demonstrate gene expression of AdipoR1 and AdipoR2 in human adipose tissue for the first time, and show that these are differentially regulated by PRL and GH. Both PRL and GH reduced adiponectin secretion in human adipose tissue in vitro and in mice in vivo. Decreased serum adiponectin levels have been associated with insulin resistance, and our data in human tissue and in transgenic mice suggest a role for adiponectin in PRL and GH induced insulin resistance.
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PMID:Prolactin and growth hormone regulate adiponectin secretion and receptor expression in adipose tissue. 1588 93

Obese (fa/fa) Zucker rat is a spontaneous genetic obesity model and, by comparison with lean Zucker rat, exhibits hyperphagia, hyperinsulinemia, and hyperlipidemia. The aim of this study was to examine the physiological difference concerning adiponectin between obese (fa/fa) Zucker rats and control lean Zucker rats. We therefore measured plasma adiponectin level and analyzed adiponectin and adiponectin receptor 1 mRNA expression in retroperitoneal white adipose tissue (RT WAT), brown adipose tissue (BAT), liver, and soleus muscle. We also examined the tissue mRNA expression of peroxisome proliferator-activated receptor alpha (PPAR alpha), PPAR delta, and PPAR gamma, which regulate adiponectin expression sensitivity to a PPAR gamma agonist shown by brown adipocytes from obese (fa/fa) Zucker rats and lean Zucker rats, by measuring adiponectin release from these cells. Plasma adiponectin levels of obese (fa/fa) Zucker rats were significantly higher than those of lean Zucker rats. Adiponectin mRNA expression levels in RT WAT were lower in obese (fa/fa) Zucker rats than in lean Zucker rats, but those in BAT were higher. Adiponectin receptor 1 expression levels in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats were lower than in lean Zucker rats. The expression level of PPAR alpha, PPAR delta, and PPAR gamma in BAT was lower in obese (fa/fa) Zucker rats than in lean Zucker rats. Moreover, the PPAR gamma agonist increased adiponectin release only from the brown adipocytes isolated from lean Zucker rats. It is the conclusive difference between obese (fa/fa) Zucker rats and lean Zucker rats that plasma adiponectin levels of obese (fa/fa) Zucker rats are significantly higher than those of lean Zucker rats. Moreover, we clarified that mRNA expression level of adiponectin receptor 1 in RT WAT, BAT, and liver of obese (fa/fa) Zucker rats is low despite high plasma adiponectin level, and low expression of PPARs in BAT leads to less sensibility of adiponectin release from brown adipocytes to a PPAR gamma agonist in obese (fa/fa) Zucker rats.
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PMID:Physiological difference between obese (fa/fa) Zucker rats and lean Zucker rats concerning adiponectin. 1609 47

Obesity is associated with low-grade inflammation, insulin resistance, type 2 diabetes, and cardiovascular disease. This study investigated the effect of a 15-wk lifestyle intervention (hypocaloric diet and daily exercise) on inflammatory markers in plasma, adipose tissue (AT), and skeletal muscle (SM) in 27 severely obese subjects (mean body mass index: 45.8 kg/m2). Plasma samples, subcutaneous abdominal AT biopsies, and vastus lateralis SM biopsies were obtained before and after the intervention and analyzed by ELISA and RT-PCR. The intervention reduced body weight (P < 0.001) and increased insulin sensitivity (homeostasis model assessment; P < 0.05). Plasma adiponectin (P < 0.001) increased, and C-reactive protein (P < 0.05), IL-6 (P < 0.01), IL-8 (P < 0.05), and monocyte chemoattractant protein-1 (P < 0.01) decreased. AT inflammation was reduced, determined from an increased mRNA expression of adiponectin (P < 0.001) and a decreased expression of macrophage-specific markers (CD14, CD68), IL-6, IL-8, and tumor necrosis factor-alpha (P < 0.01). After adjusting for macrophage infiltration in AT, only IL-6 mRNA was decreased (P < 0.05). Only very low levels of inflammatory markers were found in SM. The intervention had no effect on adiponectin receptor 1 and 2 mRNA in AT or SM. Thus hypocaloric diet and increased physical activity improved insulin sensitivity and reduced low-grade inflammation. Markers of inflammation were particularly reduced in AT, whereas SM does not contribute to this attenuation of whole body inflammation.
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PMID:Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects. 1635 67

Adiponectin is a metabolic link between adipose tissue and insulin action, mediating part of obesity-associated insulin resistance and type 2 diabetes. Two adiponectin receptors have been identified, and we investigated whether sequence variations in adiponectin receptor 1 (ADIPOR1) and adiponectin receptor 2 (ADIPOR2) genes could contribute to the genetic risk for type 2 diabetes in a case-control study of 1,498 Caucasian subjects. We sequenced the putative functional regions of the two genes in 48 subjects and selected single nucleotide polymorphisms (SNPs) from the public database. Five SNPs in ADIPOR1 and 12 in ADIPOR2 were tested for association with type 2 diabetes. No SNP of ADIPOR1 showed association in any of the samples from the French population. In contrast, three SNPs of ADIPOR2 showed nominal evidence for association with type 2 diabetes before correction for multiple testing (odds ratio [OR] 1.29-1.37, P = 0.034-0.014); only rs767870, located in intron 6, was replicated in an additional diabetes dataset (n = 636, OR 1.29, P = 0.020) with significant allelic association from the overall meta-analysis of 2,876 subjects (adjusted OR 1.25 [95% CI 1.07-1.45], P = 0.0051). In conclusion, our data suggest a modest contribution of ADIPOR2 variants in diabetes risk in the French population.
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PMID:Genetic analysis of ADIPOR1 and ADIPOR2 candidate polymorphisms for type 2 diabetes in the Caucasian population. 1650 55

Type-2 diabetes is characterized by obesity-related insulin resistance. Insulin resistance and accompanying hyperinsulinemia have been reported to play an important role in pathogenesis of the metabolic syndrome. Conjugated linoleic acid (CLA), a mixture of positional and geometric isomers of linoleic acid, has attracted considerable attention because of its potentially beneficial biological effects. Previous studies showed that dietary CLA alleviates diabetes through improvement of glucose tolerance and insulin-stimulated glucose transport activity in skeletal muscle of diabetic rats. Skeletal muscle plays an important role both in insulin-mediated glucose metabolism and in lipid metabolism. In the present study, we evaluated comprehensively the effect of dietary CLA on the expression of genes related to lipid metabolism and insulin sensitivity in the skeletal muscle of obese, diabetic Zucker rats. After 8 weeks of feeding, expression of lipogenic genes was decreased in tendency, while expression of lipolytic genes was markedly increased by dietary CLA. Additionally, expression of genes-related insulin sensitivity, such as adiponectin receptor 1, was significantly enhanced, and mRNA level of peroxisome proliferator activated receptor-alpha, known as a transcriptional factor related lipid metabolism and insulin signaling in skeletal muscle, was markedly increased in CLA-fed rats. We also showed that dietary CLA significantly decreased the level of tumor necrosis factor-alpha (TNF-alpha), associated with the development of insulin resistance, in the skeletal muscle of Zucker rats. We suppose that the attenuated TNF-alpha accumulation in skeletal muscle may contribute to the alteration of expression of several genes and the alleviation of insulin resistance in CLA-fed Zucker rats.
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PMID:Dietary conjugated linoleic acid lowered tumor necrosis factor-alpha content and altered expression of genes related to lipid metabolism and insulin sensitivity in the skeletal muscle of Zucker rats. 1700 73

Nutritional control of molecular events has become of great interest given the increased incidence of diet-induced obesity, and consequently Type 2 (non-insulin-dependent) diabetes, in recent years. The altered adipose tissue content in obese individuals results in an altered profile of circulating adipokines, and here we focus on adiponectin, whose circulating levels decrease in obese individuals. Adiponectin is a 30 kDa protein but circulates primarily as hexameric, oligomeric and, to a lesser extent, trimeric forms. Full-length adiponectin can also be cleaved to produce a fragment containing the globular domain that exerts potent metabolic effects. Adiponectin has insulin-mimetic and -sensitizing actions including stimulation of glucose uptake in skeletal muscle and suppression of glucose production in liver. Hence, adiponectin has attracted great interest as an antidiabetic agent. Adiponectin acts via two receptor isoforms, AdipoR1 (adiponectin receptor 1) and AdipoR2, which have distinct tissue distributions and affinities for recognition of the various adiponectin forms. Expression of AdipoR isoforms can be regulated by hyperinsulinaemia and hyperglycaemia with the consequence of increased sensitivity or resistance to specific forms of adiponectin. In summary, regulation of adiponectin or AdipoR expression may be of great importance in the development of metabolic perturbations characteristic of Type 2 diabetes in obese individuals.
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PMID:Mechanisms regulating energy metabolism by adiponectin in obesity and diabetes. 1705 1

Adiponectin, a hormone secreted by adipose tissue, circulates at high concentrations in human plasma. Paradoxically, plasma levels of adiponectin are approximately 50% lower in obese than in lean subjects. An association between low plasma levels of adiponectin and higher risk of developing breast and other cancers was recently reported. Obesity and overweight have also been associated with increased mortality from cancer. To test the hypothesis that adiponectin exerts direct antiproliferative and/or pro-apoptotic effects on cancer cells, we used the MCF7 human breast adenocarcinoma cell line. The proliferation rate of the MCF7 cells was measured using the MTT method, while apoptosis was examined by quantifying the DNA fragmentation using an ELISA assay. In addition, adiponectin receptor 1 (AdipoR1) and AdipoR2 mRNA expression was detected using RT-PCR. Adiponectin diminished the proliferation rate of MCF7 cells; this effect was significant after 48-96 hours of treatment. The presence of receptor expression suggested that the effect of adiponectin on cell proliferation was most likely specific and adiponectin receptor-mediated. Adiponectin induced no apoptosis of MCF7 cells over 48 hours. We conclude that adiponectin inhibits proliferation but causes no apoptosis of MCF7 breast cancer cells. These data suggest that adiponectin may represent a direct hormonal link between obesity and cancer.
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PMID:Antiproliferative effect of adiponectin on MCF7 breast cancer cells: a potential hormonal link between obesity and cancer. 1722 7

Adiponectin and visfatin are newly discovered adipokines that are strongly expressed in human visceral adipose tissue. To identify new regulatory mechanisms in fat, the effect of TNF-alpha (TNF) on adiponectin, on its two receptors, and on visfatin was investigated by incubating human visceral adipose tissue from patients without diabetes mellitus with TNF for 24, 48 and 72 hours. The mRNA expression of visfatin, adiponectin, and its two receptors, as well as the protein expression of adiponectin were determined. A decrease of adiponectin mRNA expression of 97% after incubation with TNF (5.75 nmol/l) for 24 hours, a decrease of 91% after 48 hours, and a decrease of 96% after 72 hours were measured. The reduction of protein expression was measured to be 42% after 24 hours, 28% after 48 hours, and 39% after 72 hours of incubation with TNF (5.75 nmol/l). The mRNA level of adiponectin receptor 1 (AdipoR1) was elevated about 72% after 48 hours of incubation and 67% after 72 hours of incubation, whereas the mRNA expression of adiponectin receptor 2 (AdipoR2) was not altered significantly. The visfatin mRNA level was found to be highly increased by 255% after 24 hours and 335% after 48 hours and 341% after 72 hours of incubation with TNF (5.75 nmol/l). Our results support the concept of visceral adipose tissue as an endocrine organ. We demonstrate that TNF has regulatory functions on adiponectin, AdipoR1 and on visfatin in human visceral adipose tissue. TNF levels are elevated in states of obesity and insulin resistance. Due to this fact TNF could be the reason that there is a decrease in the level of adiponectin, whereas there is an increase in the level of visfatin in states of obesity and insulin resistance.
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PMID:TNF-alpha alters visfatin and adiponectin levels in human fat. 1744 61


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