Adipose Tissue Resistin Expression Is Severely Suppressed in Obesity and Stimulated by Peroxisome Proliferator-activated Receptor γ Agonists

Way, James M.; Görgün, Cem Z.; Tong, Qiang; Uysal, K. Teoman; Brown, Kathleen K.; Harrington, W. Wallace; Oliver, William R.; Willson, Timothy M.; Kliewer, Steven A.; Hotamışlıgil, Gökhan S.

doi:10.1074/jbc.c100189200

Cited by 383 publications

(301 citation statements)

References 13 publications

Supporting

Mentioning

265

Contrasting

Unclassified

Order By: Relevance

“…Secondly, results from studies determining expression and regulation of this adipocytokine are contradictory. Thus, severely decreased resistin mRNA levels have been observed in different mouse models of obesity and insulin resistance such as ob/ob, db/db, tub/tub, and KKA γ mice (Table 1) [60]. These findings are supported and extended by other groups indicating that resistin is down-regulated in diet-induced obesity in mice [61], in fructose-fed obese rats [62], in fa/fa rats [63], and in KK mice [64].…”

Section: Resistinsupporting

confidence: 57%

“…In accordance with the original observations, PPARγ-activators such as troglitazone, rosiglitazone, and darglitazone potently down-regulate resistin mRNA by approximately 80% to 90% in 3T3-L1 adipocytes in vitro [65,66] and resistin mRNA is down-regulated by 72% in db/db mice after rosiglitazone treatment [67]. In contrast, up-regulation of resistin mRNA expression has been observed after treatment of male ob/ob mice and ZDF rats with the PPARγ-agonists MC-555, rosiglitazone, and GW1929 for 7 days [60]. Similarly, consistent upregulation of resistin mRNA has been shown in white fat after treatment with the PPARγ-agonists NC-2100, pioglitazone, and troglitazone [64].…”

Section: Resistinmentioning

confidence: 99%

“…Furthermore, insulin down-regulates resistin gene expression in 3T3-L1 adipocytes in vitro (Table 1) [65,66]. However, administration of insulin to streptozotocin-diabetic mice [69] or ZDF rats [60] consistently stimulates resistin mRNA synthesis in vivo and a dose-dependent increase of 3T3-L1 adipocyte resistin secretion after insulin treatment for 24 h has been described [70]. Two independent studies suggest that the glucocorticoid dexamethasone induces resistin mRNA and protein expression in 3T3-L1 fat cells by up to 3.5-fold [65,66]; however, a third study from our laboratory did not find any effect in the same cell line (Table 1) [68].…”

Section: Resistinmentioning

confidence: 99%

See 2 more Smart Citations

Regulation of adipocytokines and insulin resistance

2003

View full text Add to dashboard Cite

It has long been known that obesity and insulin resistance are linked. Recently, it has been shown that adipocytes secrete several proteins including tumour necrosis factor-α, interleukin-6, resistin, and adiponectin. Since several of these so-called adipocytokines influence insulin sensitivity and glucose metabolism profoundly, they might provide a molecular link between increased adiposity and impaired insulin sensitivity. Thiazolidinediones which decrease insulin resistance and are used in the treatment of Type 2 diabetes seem to mediate part of their insulin-sensitising effects via modulation of adipocytokine expression.Furthermore, hormones such as β-adrenergic agonists, insulin, glucocorticoids, and growth hormone might impair insulin sensitivity at least in part via up-regulation or down-regulation of adipocytokine synthesis. We summarise the current knowledge on how major adipocyte-secreted proteins are regulated by hormones and drugs influencing insulin sensitivity and discuss its implications for insulin resistance and obesity. [Diabetologia (2003[Diabetologia ( ) 46:1594[Diabetologia ( -1603

show abstract

Section: Resistinsupporting

confidence: 57%

Section: Resistinmentioning

confidence: 99%

Section: Resistinmentioning

confidence: 99%

See 1 more Smart Citation

Regulation of adipocytokines and insulin resistance

2003

View full text Add to dashboard Cite

show abstract

“…The identity of resistin amino acid sequences in mouse and human proteins is only 59% [6] and because of this incomplete homology resistin may have different physiological roles in different species [7]. In fact, studies in humans reported conflicting results, indicating decreased or increased resistin levels in obesity, opposite responses to insulin-sensitisers and contradictory correlations between resistin and markers of insulin resistance [8][9][10][11][12][13][14][15]. It has also been suggested that resistin plays a role in inflammatory conditions, because it is expressed in human macrophages [16] and because recent data have supported the existence of an independent association of resistin with the inflammatory factors IL-6 and C-reactive protein [17].…”

Section: Introductionmentioning

confidence: 99%

Increased serum resistin in elite endurance athletes with high insulin sensitivity

et al. 2006

View full text Add to dashboard Cite

Aims/hypothesis: Resistin is an adipokine associated with obesity and type 2 diabetes in animal models, but in humans its role remains uncertain. This study was undertaken to test whether serum resistin is related to insulin resistance and markers of low-grade inflammation in elite athletes taken as a model of extreme insulin sensitivity. Subjects materials and methods: In 23 elite athletes (sprinters, middle-distance and marathon runners) and in 72 sedentary men including lean and obese individuals with NGT, and obese individuals with IGT or new-onset type 2 diabetes, we assessed insulin sensitivity using a whole-body insulin-sensitivity index (WBISI) derived from a 3-h OGTT; energy homeostasis was also assessed by means of indirect calorimetry, along with circulating adipokines and low-grade pro-inflammatory cyto-chemokines.Results: Professional athletes had increased WBISIs (p<0.001) and lipid oxidation (p<0.03); they also showed higher serum resistin concentrations (p<0.001), although the pro-inflammatory chemokines were not increased in comparison with the other study groups. Resistin was independently associated only with fasting plasma NEFA. Increased resistin was detected in the middle-distance and marathon runners, but not in the sprinters when compared with the lean, young, sedentary individuals. Conclusions/interpretation: Serum resistin concentration is increased in elite athletes, providing evidence against the notion that resistin levels reflect insulin resistance in humans, as seen in animal studies. Increased resistin was observed in aerobicendurance, but not sustained-power athletes and this feature appeared to be independently associated with parameters of fatty acid metabolism.

show abstract

“…The transgenic overexpression of resistin impairs skeletal muscle glucose metabolism and promotes glucose intolerance [5]. In contrast, some reports demonstrate that a high level of resistin is not related to obesity or insulin resistance [6][7][8]. In particular, several studies with human resistin do not show any association between resistin expression and insulin resistance [9,10].…”

Section: Introductionmentioning

confidence: 99%

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

et al. 2005

View full text Add to dashboard Cite

Aims/hypothesis: Resistin is an adipokine that might link obesity and insulin resistance. A common polymorphism of the human resistin gene, −420C>G, is a major determinant of plasma resistin concentrations as well as resistin mRNA expression in human adipose tissue. In this study, we investigated the regulatory mechanism by which this polymorphism affects resistin expression. Methods: Electrophoretic mobility shift assay was performed to identify the transcription factors binding to the −420G region. Transient transfection and reporter assay were used to measure promoter activities of the resistin gene. The binding ability of stimulatory protein 1 (Sp1) in response to adipocyte differentiation or high glucose concentrations was also measured. Results: Sp1 and stimulatory protein 3 (Sp3) specifically bound to the region around −420G of the human resistin gene. Overexpression of Sp1 increased the promoter activity regardless of −420 genotypes, while the promoter activity of the −420G construct was two-fold higher than that of the −420C construct. In contrast, overexpression of Sp3 scarcely increased the promoter activity. The binding ability of Sp1 to the −420G region was increased in response to adipocyte differentiation. Mithramycin A, an inhibitor of DNA binding of Sp1, reduced the effect of high glucose on transcription induction of the resistin gene in adipocytes. Conclusions/interpretation: These results suggest that Sp1 is an important factor regulating transcription of human resistin gene. A common polymorphism of the human resistin promoter, −420C>G, is critical for the binding of Sp1 and modulates the transcriptional activity of the resistin gene by changing the binding ability of Sp1. In addition, Sp1 may be involved in the increase of resistin expression by hyperglycaemia.

show abstract

Adipose Tissue Resistin Expression Is Severely Suppressed in Obesity and Stimulated by Peroxisome Proliferator-activated Receptor γ Agonists

Cited by 383 publications

References 13 publications

Regulation of adipocytokines and insulin resistance

Regulation of adipocytokines and insulin resistance

Increased serum resistin in elite endurance athletes with high insulin sensitivity

Regulation of human resistin gene expression in cell systems: an important role of stimulatory protein 1 interaction with a common promoter polymorphic site

Contact Info

Product

Resources

About