Aims/hypothesis We investigated whether oltipraz, a nuclear respiratory factor 2 alpha subunit (NRF2) activator, improves insulin sensitivity and prevents the development of obesity in mice. Methods C57BL/6J mice were fed with a low-fat diet (10% of energy as fat), a high-fat diet (HFD) (45% of energy as fat) or a HFD with oltipraz for 28 weeks. The effects of oltipraz on body weight, fat content, glucose disposal, insulin signalling, metabolic profiles and endogenous NRF2 functional status in the three groups of mice were investigated. Results Oltipraz prevented or significantly attenuated the effect of HFD on glucose disposal, body weight and fat gain. Impairment of protein kinase B/Akt phosphorylation in this HFD-fed mouse model in response to intraperitoneal insulin injection was observed in adipose tissue, but not in the muscles, accompanied by inhibition of AMP-activated protein kinase signalling and activation of p70S6 kinase, as well as reduced GLUT4 content. These defects were Z. Yu and W. Shao contributed equally to this study. Diabetologia (2011) 54:922-934 DOI 10.1007/s00125-010-2001 attenuated by oltipraz administration. Nuclear content of NRF2 in adipose tissue was reduced by HFD feeding, associated with increased Keap1 mRNA expression and reduced production of haem oxygenase-1 and superoxide dismutase, increased protein oxidation, decreased plasma reduced:oxidised glutathione ratio and the appearance of macrophage marker F4/80. These defects were also restored by oltipraz. Finally, oltipraz attenuated HFD-induced inducible nitric oxide synthase overproduction. Conclusions/interpretation Impairment of the endogenous redox system is important in the development of obesity and insulin resistance in chronic HFD feeding. NRF2 activation represents a potential novel approach in the treatment and prevention of obesity and diabetes. Electronic supplementary material
Unfortunately, the abbreviation NRF2 was incorrectly defined in the title and in the article as 'nuclear respiratory factor 2 alpha subunit', whereas it should have read 'nuclear factor (erythroid-derived 2)-like 2'.
Large leaf gentian, Gentiana macrophylla Pall., known as Qin Jiao in Chinese, is a medicinal herb. Its root is most commonly used in Chinese traditional medicine to relieve rheumatic conditions and to remove damp-heat. During a survey in July 2009, large leaf gentian plants exhibiting foliar chlorotic and necrotic spots as well as severe stunting were collected in Lijiang County, Yunnan Province of China. Incidence of symptomatic plants ranged from 10 to 30% in the field. Symptomatic leaves from five different G. macrophylla plants were collected and tested for Impatiens necrotic spot virus (INSV), Tomato spotted wilt virus, Watermelon silver mottle virus, Groundnut bud necrosis virus, Tomato chlorotic spot virus, and Groundnut ringspot virus by double-antibody sandwich-ELISA kits (Agdia Inc., Elkhart, IN). All tested samples were positive only for INSV. To further confirm the presence of INSV, reverse transcription (RT)-PCR was conducted. Total RNA was extracted from the symptomatic large leaf gentian plants leaves with a RNeasy Plant Kit (Qiagen Inc., Valencia, CA) and used as a template in RT-PCR using forward (5′-CTT TGC TTT TTA GAA CTG TGC A-3′) and reverse (5′-AGA GCA ATT GTG TCA CGA ATA T-3′) primers specific to the partial INSV nucleoprotein (N) gene (GenBank No. DQ425096). Amplicons of the expected size (approximately 760 bp) were obtained from all ELISA-positive samples. Three clones were sequenced and the partial nucleocapsid protein genes consensus sequences of these isolates were determined (GenBank No. HQ317133). Nucleotide sequences of large leaf gentian isolates shared 98 to 99% nucleotide identity with INSV sequences of isolates from China, Italy, Japan, United States, and the Netherlands (GenBank Nos. FN400772, GQ336989, DQ425096, AB109100, D00914, AB109100, and X66972). INSV is one of the most serious viral pathogens of ornamental plants in North America, Europe, and Asia (1–3). To our knowledge, this is the first report of natural occurrence of INSV in G. macrophylla in China. References: (1) S. T. Koike. Plant Dis. 92:1248, 2008. (2) E. K. Tóth et al. Plant Dis. 91:331, 2007. (3) Q. Zhang et al. Plant Dis. 94:915, 2010.
We report on measurements of mass and total decay width of the W boson and of triple-gauge-boson couplings, WW and ZWW, with the L3 detector at LEP. W-pair events produced in e + e interactions between 161 GeV and 172 GeV centreof-mass energy are selected in a data sample corresponding to a total luminosity of 21.2 pb 1 . The mass and total decay width of the W boson are determined to be M W = 80:75 +0:26 0:27 (exp:) 0:03 (LEP) GeV and W = 1:74 +0:88 0:78 (stat:) 0:25 (syst:) G e V, respectively. Limits on anomalous triple-gauge-boson couplings, WW and ZWW, are determined, in particular 1:5 < Z < 1 : 9 (95% CL), excluding vanishing ZWW coupling at more than 95% condence level. Submitted to Phys. Lett. B 1 IntroductionFor the 1996 data taking period, the centre-of-mass energy, p s, of the e + e collider LEP at CERN was increased to 161 GeV, 170 GeV and 172 GeV. This allowed for the rst time the pair-production of on-shell W bosons in e + e interactions, e + e ! W + W . Analysis of Wpair production adds important knowledge to the Standard Model of electroweak interactions [1] through the measurements of mass and width of the W boson and of the triple-gauge-boson couplings WW and ZWW [2,3]. These parameters were rst measured at p p colliders [4{6].The total W-pair production cross section as calculated within the Standard Model depends on p s and on the mass and total width of the W boson, M W and W . Results for M W derived from total cross section measurements have been published by L3 [7, 8] and the other LEP experiments [9,10]. In this letter a more precise determination of M W and a rst determination of W is presented based on the invariant mass of the W-boson decay products.To lowest order within the Standard Model, three Feynman diagrams contribute to Wpair production, the s-channel and Z-boson exchange and the t-channel e exchange. The s-channel diagrams arise as a consequence of the triple-gauge-boson vertices WW and ZWW which are expected due to the non-Abelian gauge structure of the electroweak theory [1,3]. Results for triple-gauge-boson couplings derived from the data collected at p s = 161 GeV h a v e been published by L3 [7, 11] and the other LEP experiments [10,12]. Here a determination of triple-gauge-boson couplings is presented based on total and dierential cross sections in W-pair mediated four-fermion production.The L3 detector is described in detail in Reference 13. During the 1996 run the L3 detector collected total integrated luminosities of 10.9 pb 1 at p s = 161:34 GeV (threshold data), and 1.0 pb 1 and 9.3 pb 1 at p s = 170:31 GeV and at p s = 172:32 GeV (high-energy data). These centre-of-mass energies are known to 0:06 GeV [14]. The results obtained at threshold and from the high-energy data are combined to determine the mass of the W boson and triplegauge-boson couplings. Analysis of Four-Fermion ProductionThe W boson decays into a quark-antiquark pair, such a s W ! ud or cs, or a lepton-antilepton pair, W !` `(`= e ; ; ); in the following denoted as qq,` or f f in general fo...
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