Disease relevance of Retn

• Resistin/ADSF/FIZZ3 in obesity and diabetes [1].
• Adipose resistin expression and serum resistin increased in response to hyperinsulinemia and further in response to hyperglycemia [2].
• Finally, acute hyperglycemia leads to up-regulation of resistin and RELMalpha transcription in various adipose depots [3].
• Decreases in Rstn production and secretion induced by IGF-I may be related to the mechanism by which IGF-I modulates body weight and diabetes in animals [4].
• Weight loss in tumour-bearing mice is not associated with changes in resistin gene expression in white adipose tissue [5].

Psychiatry related information on Retn

• In a third set of experiments we examined the influence of food deprivation on pituitary and fat resistin mRNA [6].

High impact information on Retn

• 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 [7].
• We investigated the chronic in vivo effect of resistin on insulin sensitivity and glucose metabolism by overexpressing resistin protein in male Wistar rats using intravenous administration of an adenovirus encoding mouse resistin [8].
• The glucose clamp studies were performed at submaximal (4 mU/kg/min) and maximal (25 mU/kg/min) insulin infusion rates and demonstrated the presence of insulin resistance induced by elevated resistin levels [8].
• After 7 days of elevated resistin levels at a supraphysiological concentration, the animals displayed glucose intolerance and hyperinsulinemia during glucose tolerance tests, and insulin tolerance tests demonstrated an impaired glucose-lowering effect of insulin [8].
• Resistin is an adipose-derived hormone postulated to link adiposity to insulin resistance [9].

Chemical compound and disease context of Retn

• Changes in glycemia by leptin administration or high- fat feeding in rodent models of obesity/type 2 diabetes suggest a link between resistin expression and control of glucose homeostasis [10].
• These data collectively suggest that resistin expression may be suppressed by hyperinsulinemia and that metformin may upregulate resistin expression via the improvement of hyperinsulinemia in obesity [11].
• In conclusion, telmisartan treatment might prevent the development of obesity and related metabolic disorders by altering the levels of adiponectin, resistin, and uncoupling protein 1 in diet-induced obese mice [12].

Biological context of Retn

• Using reverse transcription polymerase chain reaction (RT-PCR) we show that the resistin gene (Retn) is expressed in mouse brain (hypothalamus and cortex) and pituitary gland [13].
• ADSF has been implicated in modulating adipogenesis and insulin resistance [14].
• To examine the long-term function of ADSF in adipogenesis and glucose homeostasis, we constructed an expression vector for a dominant inhibitory form of ADSF by fusing it to the human IgGgamma constant region (hFc) [14].
• This finding clearly demonstrates in vivo the inhibitory role of ADSF in adipogenesis [14].
• Interestingly, in both ob/ob and high fat-fed mice we obtained a striking positive correlation between glycemia and resistin gene expression [10].

Anatomical context of Retn

• This peak in pituitary Retn mRNA was unaffected by early weaning but was abolished by neonatal treatment with monosodium glutamate, suggesting that the basal hypothalamus regulates pituitary Retn [13].
• Mouse Cebpe and Retnlg were predictably expressed in macrophages, whereas Retn was abundant in adipocytes [15].
• Resistin is an adipocyte hormone that modulates glucose homeostasis [16].
• Resistin, a 10-kDa adipose tissue specific secretory protein, has recently been implicated in exerting a negative effect on systemic insulin sensitivity [3].
• Immunohistochemistry revealed resistin protein in the arcuate nucleus and pituitary gland [13].

Associations of Retn with chemical compounds

• ADSF-hFc transgenic mice with impaired ADSF function exhibit improved glucose tolerance and insulin sensitivity either on chow or high-fat diets [14].
• Treatment with either actinomycin D or cycloheximide prevented E2-stimulated resistin mRNA expression, suggesting that the effect of E2 requires new mRNA and protein synthesis [17].
• Using 3T3-L1 adipocytes, we found that 17 beta-estradiol (E2) up-regulated resistin mRNA expression in a dose- and time-dependent manner [17].
• Moreover, PD98059, but not SB203580 or LY294002, antagonized E2-increased resistin protein release [17].
• Neither SB203580 nor LY294002 changed the E2-increased levels of resistin mRNA, but they respectively inhibited E2-stimulated phosphorylation of p38 MAPK and Akt [17].

Regulatory relationships of Retn

• Remarkably, resistin treatment markedly induces the gene expression of suppressor of cytokine signaling 3 (SOCS-3), a known inhibitor of insulin signaling [16].
• We found that IGF-I suppressed Rstn mRNA expression and protein release in dose- and time-dependent manners [4].
• Endothelin-1 inhibits resistin secretion in 3T3-L1 adipocytes [18].
• Overexpression with MEK1 blocked EGCG-inhibited Rstn mRNA expression [19].
• Furthermore, suppression of resistin mRNA levels could be completely reversed to control levels by withdrawal of TNFalpha for 24 h [20].

Other interactions of Retn

• SOCS-3 induction is the first cellular effect of resistin that is independent of insulin and is a likely mediator of resistin's inhibitory effect on insulin signaling in adipocytes [16].
• 17 beta-estradiol stimulates resistin gene expression in 3T3-L1 adipocytes via the estrogen receptor, extracellularly regulated kinase, and CCAAT/enhancer binding protein-alpha pathways [17].
• Adiponectin and resistin, two recently identified adipocyte-specific secretory factors, are able to modulate insulin actions in target tissues [21].
• However, SB-203580 antagonized the IGF-I-decreased Rstn protein release [4].
• Resistin-like molecule-alpha (RELMalpha), a homolog of resistin originally identified by its upregulation in asthmatic lung, is another secreted protein expressed in adipose tissue [3].

Analytical, diagnostic and therapeutic context of Retn

• Semi-quantitative RT-PCR analysis indicated that Retn mRNA is developmentally regulated in the pituitary [13].
• Plasma leptin levels were also increased by ovariectomy, whereas resistin and adiponectin levels were unchanged [22].
• Castration did not abolish gender differences in plasma levels or resistin, adiponectin, or leptin mRNAs [22].
• At the end of the incubation period, resistin secretion was determined in the media by immunoblotting and densitometric analysis [18].
• Elevated plasma resistin levels in mice treated with the resistin adenovirus (AdmRes) were confirmed by Western blotting analysis and RIAs [23].

References