NLRC5 affects diet-induced adiposity in female mice and co-regulates peroxisome proliferator-activated receptor PPARγ target genes

被引：4

作者：

Bauer, Sarah ^{[1
]}

Aeissen, Vanessa ^{[1
]}

Bubeck, Alena M. ^{[2
]}

Kienes, Ioannis ^{[1
]}

Ellwanger, Kornelia ^{[1
,5
]}

Scheurenbrand, Mona ^{[2
]}

Rexhepi, Fjolla ^{[3
]}

Ramanathan, Sheela ^{[3
]}

Rosenstiel, Philip ^{[4
]}

Fricke, W. Florian ^{[2
]}

Kufer, Thomas A. ^{[1
]}

机构：

[1] Univ Hohenheim, Inst Nutr Med, Dept Immunol, D-70599 Stuttgart, Germany

[2] Univ Hohenheim, Inst Nutr Sci, Dept Microbiome & Appl Bioinformat, D-70599 Stuttgart, Germany

[3] Univ Sherbrooke, Fac Med & Hlth Sci, Dept Immunol & Cell Biol, Sherbrooke, PQ J1H 5N4, Canada

[4] Christian Albrechts Univ Kiel, Inst Clin Mol Biol, D-24105 Kiel, Germany

[5] Univ Hosp Tubingen, Inst Med Genet & Appl Genom, Calwerstr 7, D-72076 Tubingen, Germany

来源：

ISCIENCE | 2023年 / 26卷 / 04期

基金：

加拿大健康研究院;

关键词：

MHC CLASS-I; NUCLEOTIDE-BINDING DOMAIN; DOMINANT-NEGATIVE MUTATIONS; FAMILY-MEMBER NLRC5; NOD-LIKE RECEPTORS; HIGH-FAT DIET; NF-KAPPA-B; INSULIN-RESISTANCE; INNATE IMMUNITY; TRANSCRIPTIONAL REGULATOR;

D O I：

10.1016/j.isci.2023.106313

中图分类号：

O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

Nucleotide-binding and oligomerization domain containing 5 (NLRC5) is the key transcriptional regulator of major histocompatibility (MHC) class I genes. Recent observations suggest a role for NLRC5 in metabolic traits and in transcriptional regulation beyond MHC class I genes. To understand the function of NLRC5 in metabolic disease, we subjected Nlrc5(-/-) mice to high-fat diet (HFD) feeding. Fe-male Nlrc5(-/-) mice presented with higher weight gain and more adipose tissue (AT) compared to wild-type (WT) animals. Mechanistically, we demonstrate that NLRC5 enhanced the expression of peroxisome proliferator-activated receptor (PPAR) gamma target genes in human cells. We identify Sin3A and negative elongation factor (NELF) B as two novel NLRC5 interaction partners and show that Sin3A partly modulates the synergistic transcriptional effect of NLRC5 on PPAR gamma. Collectively, we show that NLRC5 contributes to weight gain in mice, which in-volves transcriptional enhancement of PPAR gamma targets by NLRC5 that is co -regulated by Sin3A.

引用

页数：27

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