Disease relevance of RETN

• The adipokine resistin is suggested to be an important link between obesity and insulin resistance [1].
• Resistin, an adipokine/cytokine, is involved in inflammatory processes that could lead to insulin resistance status and vascular diseases [2].
• Furthermore, ectopic expression of ADD1/SREBP1c by adenovirus significantly increased the expression of resistin mRNA in adipocytes [3].
• We developed an ELISA for human resistin and measured plasma concentrations in aged individuals with or without type 2 diabetes mellitus [4].
• We determined resistin levels and metabolic parameters in 24 HIV-infected men and women with lipoatrophy and hyperinsulinemia and studied the effect of 12 wk of the peroxisome proliferator-activated receptor-gamma agonist rosiglitazone (4-8 mg/d) on resistin in these subjects [5].

Psychiatry related information on RETN

• Serum adiponectin and resistin concentrations in patients with restrictive and binge/purge form of anorexia nervosa and bulimia nervosa [6].
• In conclusion, circulating concentrations of leptin, adiponectin and resistin are markedly altered in patients with chronic heroin addiction [7].
• Serum resistin concentrations and ISI were not affected by alcohol consumption [8].
• Expression of resistin is low during food deprivation and in diabetes, and increased greatly during refeeding and insulin treatment [9].

High impact information on RETN

• Resistin, obesity and insulin resistance--the emerging role of the adipocyte as an endocrine organ [10].
• The hormone resistin links obesity to diabetes [11].
• Moreover, treatment of normal mice with recombinant resistin impairs glucose tolerance and insulin action [11].
• Fat cells produce peptides that can elicit insulin resistance, such as tumor necrosis factor-alpha and resistin, as well as hormones that can improve insulin resistance, such as leptin and adiponectin [12].
• After intravenous injection of Schistosoma mansoni eggs, IL-31Ralpha(-/-) mice developed severe pulmonary inflammation, characterized by an increase in the area of granulomatous inflammation, increased numbers of resistin-like molecule alpha(+) cells, and enhanced collagen deposition compared to WT counterparts [13].

Chemical compound and disease context of RETN

• Design and Setting: The hepatic fat (IHF) content, measured quantitatively by means of (1)H magnetic resonance spectroscopy, serum resistin, and biochemical and hormonal metabolic correlates of fatty liver and insulin resistance were assessed in 28 affected patients, and 47 individuals with comparable anthropometric features served as controls [14].
• Elevated resistin levels in cirrhosis are associated with the proinflammatory state and altered hepatic glucose metabolism but not with insulin resistance [15].
• Short-term dexamethasone administration does not alter serum adiponectin or resistin concentrations in overweight and obese subjects despite an increase in insulin resistance [16].
• We examined the effects of rosiglitazone and metformin on the plasma resistin levels in individuals with type 2 diabetes mellitus [17].
• The aim of our study was to compare circulating concentration of adipose tissue-derived hormones leptin, adiponectin and resistin in 12 patients with heroin addiction before and after one-year methadone maintenance treatment with the group of 20 age- and body mass index-matched healthy subjects [7].

Biological context of RETN

• The phosphorylation/activation of ATF-2 and its binding to PTEN promoter were increased by resistin treatment [2].
• Up-regulation of PTEN (phosphatase and tensin homolog deleted on chromosome ten) expression by resistin may mediate the inhibitory effects [2].
• In summary, up-regulation of PTEN is involved in the inhibitory effects of resistin on insulin signaling and eNOS activation in endothelial cells [2].
• To investigate the molecular mechanisms of resistin gene expression, we cloned and characterized the human resistin promoter [3].
• Expression of ADD1/SREBP1c transactivated the luciferase reporter gene activity, the promoter region of which contains a human resistin promoter in a sterol regulatory element (SRE)-dependent manner [3].

Anatomical context of RETN

• Thus, the myeloid-restricted nature of CEBPE precludes the expression of RETN in human adipocytes which, however, are targeted by this innate immune-derived proinflammatory cytokine [18].
• Quite the opposite, a low and inconsistent RETN transcription was seen in some human white adipose tissue (WAT) biopsies without any relationship to body mass index, insulin sensitivity, or fat depot [18].
• Real-time RT-PCR analysis demonstrated lack of both the transcriptional factor CEBPE and RETN expression in adipose and muscle cells [18].
• In the current study, we observed that resistin inhibited insulin signaling and eNOS activation in endothelial cells [2].
• Levels of resistin were assessed by ELISA in 74 paired blood and synovial fluid samples of patients with rheumatoid arthritis [1].

Associations of RETN with chemical compounds

• Plasma tumor necrosis factor-alpha, resistin, macrophage chemoattractant protein-1, and adiponectin concentrations were similar in the portal vein and radial artery in obese subjects [19].
• The plasma glucose concentration was an independent factor associated with log-resistin [4].
• Resistin levels in human immunodeficiency virus-infected patients with lipoatrophy decrease in response to rosiglitazone [5].
• Log-resistin did not show a significant correlation with HOMA-IR, waist circumference, body mass index, blood pressure, or total cholesterol [4].
• Serum resistin concentrations correlated positively with body mass index and testosterone in PCOS women but not in controls [20].

Regulatory relationships of RETN

• The resistin-induced cell proliferation and migration were both completely blocked by specific ERK1/2 and p38 inhibitors [21].
• Furthermore, resistin upregulates adhesion molecules and chemokines and downregulates TRAF-3, an inhibitor of CD40 ligand signaling [22].
• Resistin is expressed in human macrophages and directly regulated by PPAR gamma activators [23].
• These results suggest that resistin promotes lipid accumulation in human macrophages through its upregulating CD36 cell surface expression [24].
• Our data showed that resistin induced VEGF production and we observed that the addition of resistin stimulated endothelial cell tube formation [25].

Other interactions of RETN

• Our findings suggest that resistin-mediated inhibition of insulin signaling and eNOS activation may contribute to cardiovascular diseases [2].
• Murine mXCP1, mXCP2 and mXCP3 genes map to murine chromosome 16 and mXCP4 is positioned on chromosome 8; the hXCP1 and hXCP2 genes are located at homologous regions of chromosomes 3 and 19 [26].
• Functional characterization of the human resistin promoter with adipocyte determination- and differentiation-dependent factor 1/sterol regulatory element binding protein 1c and CCAAT enhancer binding protein-alpha [3].
• The adipocyte-derived hormones leptin [which circulates in a free form and bound to a soluble leptin receptor (sOB-R)], adiponectin, and resistin play a key role in regulating energy homeostasis and metabolism [27].
• Conclusion: Resistin may participate in more than one mechanism to influence proinflammatory cytokine release from human adipocytes, potentially via the integration of nuclear factor-kappaB and JNK signaling pathways [28].

Analytical, diagnostic and therapeutic context of RETN

• Proinflammatory properties of resistin were evaluated in animal model by intra-articular injection of resistin followed by histological evaluation of the joint [1].
• EMSA and chromatin immunoprecipitation assays demonstrated that ADD1/SREBP1c binds to the human resistin promoter in vitro and in vivo [3].
• Simple regression analysis showed that, in both genders, leptin, free leptin index, adiponectin, and resistin correlated positively with body fat mass and negatively with waist to hip ratio. sOB-R correlated negatively with body fat mass and positively with waist to hip ratio [27].
• Participants completed metabolic testing before and after rosiglitazone including fasting determination of resistin, adiponectin, and leptin levels, serum inflammatory markers, and hyperinsulinemic euglycemic clamp testing [5].
• Cross-sectionally, we monitored maternal plasma concentration of adiponectin, resistin, and leptin and their mRNA expression in abdominal subcutaneous adipose tissue and placenta from preeclamptic (PE; n = 15) and healthy pregnant (HP; n = 23) women undergoing caesarean section [29].

References