-
Je něco špatně v tomto záznamu ?
Activated Kupffer cells inhibit insulin sensitivity in obese mice
M. Tencerova, M. Aouadi, P. Vangala, SM. Nicoloro, JC. Yawe, JL. Cohen, Y. Shen, L. Garcia-Menendez, DJ. Pedersen, K. Gallagher-Dorval, RA. Perugini, OT. Gupta, MP. Czech,
Jazyk angličtina Země Spojené státy americké
Typ dokumentu časopisecké články, Research Support, N.I.H., Extramural, práce podpořená grantem
PubMed
25805830
DOI
10.1096/fj.15-270496
Knihovny.cz E-zdroje
- MeSH
- cytokiny metabolismus MeSH
- glukózový toleranční test MeSH
- injekce intravenózní MeSH
- inzulinová rezistence fyziologie MeSH
- Kupfferovy buňky metabolismus patologie MeSH
- lidé MeSH
- malá interferující RNA aplikace a dávkování genetika MeSH
- metabolismus lipidů MeSH
- myši inbrední C57BL MeSH
- myši obézní MeSH
- myši MeSH
- obezita genetika metabolismus patologie MeSH
- systémy cílené aplikace léků MeSH
- techniky in vitro MeSH
- transkripční faktor RelA antagonisté a inhibitory genetika MeSH
- umlčování genů MeSH
- ztučnělá játra genetika metabolismus patologie MeSH
- zvířata MeSH
- Check Tag
- lidé MeSH
- mužské pohlaví MeSH
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- Research Support, N.I.H., Extramural MeSH
Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF-κB, in KCs in obese mice. We used glucan-encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Following intravenous injections, GeRPs containing siRNA against p65 of the NF-κB complex caused loss of NF-κB p65 expression in KCs without disrupting NF-κB in hepatocytes or macrophages in other tissues. Silencing of NF-κB expression in KCs in obese mice decreased cytokine secretion and improved insulin sensitivity and glucose tolerance without affecting hepatic lipid accumulation. Importantly, GeRPs had no detectable toxic effect. Thus, KCs are key contributors to hepatic insulin resistance in obesity and a potential therapeutic target for metabolic disease.
- 000
- 00000naa a2200000 a 4500
- 001
- bmc15031422
- 003
- CZ-PrNML
- 005
- 20151012102758.0
- 007
- ta
- 008
- 151005s2015 xxu f 000 0|eng||
- 009
- AR
- 024 7_
- $a 10.1096/fj.15-270496 $2 doi
- 035 __
- $a (PubMed)25805830
- 040 __
- $a ABA008 $b cze $d ABA008 $e AACR2
- 041 0_
- $a eng
- 044 __
- $a xxu
- 100 1_
- $a Tencerova, Michaela $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 245 10
- $a Activated Kupffer cells inhibit insulin sensitivity in obese mice / $c M. Tencerova, M. Aouadi, P. Vangala, SM. Nicoloro, JC. Yawe, JL. Cohen, Y. Shen, L. Garcia-Menendez, DJ. Pedersen, K. Gallagher-Dorval, RA. Perugini, OT. Gupta, MP. Czech,
- 520 9_
- $a Obesity promotes insulin resistance associated with liver inflammation, elevated glucose production, and type 2 diabetes. Although insulin resistance is attenuated in genetic mouse models that suppress systemic inflammation, it is not clear whether local resident macrophages in liver, denoted Kupffer cells (KCs), directly contribute to this syndrome. We addressed this question by selectively silencing the expression of the master regulator of inflammation, NF-κB, in KCs in obese mice. We used glucan-encapsulated small interfering RNA particles (GeRPs) that selectively silence gene expression in macrophages in vivo. Following intravenous injections, GeRPs containing siRNA against p65 of the NF-κB complex caused loss of NF-κB p65 expression in KCs without disrupting NF-κB in hepatocytes or macrophages in other tissues. Silencing of NF-κB expression in KCs in obese mice decreased cytokine secretion and improved insulin sensitivity and glucose tolerance without affecting hepatic lipid accumulation. Importantly, GeRPs had no detectable toxic effect. Thus, KCs are key contributors to hepatic insulin resistance in obesity and a potential therapeutic target for metabolic disease.
- 650 _2
- $a zvířata $7 D000818
- 650 _2
- $a cytokiny $x metabolismus $7 D016207
- 650 _2
- $a systémy cílené aplikace léků $7 D016503
- 650 _2
- $a ztučnělá játra $x genetika $x metabolismus $x patologie $7 D005234
- 650 _2
- $a umlčování genů $7 D020868
- 650 _2
- $a glukózový toleranční test $7 D005951
- 650 _2
- $a lidé $7 D006801
- 650 _2
- $a techniky in vitro $7 D066298
- 650 _2
- $a injekce intravenózní $7 D007275
- 650 _2
- $a inzulinová rezistence $x fyziologie $7 D007333
- 650 _2
- $a Kupfferovy buňky $x metabolismus $x patologie $7 D007728
- 650 _2
- $a metabolismus lipidů $7 D050356
- 650 _2
- $a mužské pohlaví $7 D008297
- 650 _2
- $a myši $7 D051379
- 650 _2
- $a myši inbrední C57BL $7 D008810
- 650 _2
- $a myši obézní $7 D008820
- 650 _2
- $a obezita $x genetika $x metabolismus $x patologie $7 D009765
- 650 _2
- $a malá interferující RNA $x aplikace a dávkování $x genetika $7 D034741
- 650 _2
- $a transkripční faktor RelA $x antagonisté a inhibitory $x genetika $7 D051996
- 655 _2
- $a časopisecké články $7 D016428
- 655 _2
- $a Research Support, N.I.H., Extramural $7 D052061
- 655 _2
- $a práce podpořená grantem $7 D013485
- 700 1_
- $a Aouadi, Myriam $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA myriam.aouadi@ki.se michael.czech@umassmed.edu. $7 gn_A_00007684
- 700 1_
- $a Vangala, Pranitha $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Nicoloro, Sarah M $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Yawe, Joseph C $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Cohen, Jessica L $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Shen, Yuefei $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Garcia-Menendez, Lorena $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Pedersen, David J $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Gallagher-Dorval, Karen $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Perugini, Richard A $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Gupta, Olga T $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA.
- 700 1_
- $a Czech, Michael P $u *Program in Molecular Medicine, Department of Surgery, and Department of Pediatrics, University of Massachusetts Medical School, Worcester, Massachusetts, USA myriam.aouadi@ki.se michael.czech@umassmed.edu.
- 773 0_
- $w MED00001782 $t FASEB journal official publication of the Federation of American Societies for Experimental Biology $x 1530-6860 $g Roč. 29, č. 7 (2015), s. 2959-69
- 856 41
- $u https://pubmed.ncbi.nlm.nih.gov/25805830 $y Pubmed
- 910 __
- $a ABA008 $b sig $c sign $y a $z 0
- 990 __
- $a 20151005 $b ABA008
- 991 __
- $a 20151012102947 $b ABA008
- 999 __
- $a ok $b bmc $g 1092298 $s 914548
- BAS __
- $a 3
- BAS __
- $a PreBMC
- BMC __
- $a 2015 $b 29 $c 7 $d 2959-69 $e 20150324 $i 1530-6860 $m The FASEB journal $n FASEB J $x MED00001782
- LZP __
- $a Pubmed-20151005