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

First Author  Bauer S Year  2023
Journal  iScience Volume  26
Issue  4 Pages  106313
PubMed ID  36968073 Mgi Jnum  J:343973
Mgi Id  MGI:7450519 Doi  10.1016/j.isci.2023.106313
Citation  Bauer S, et al. (2023) NLRC5 affects diet-induced adiposity in female mice and co-regulates peroxisome proliferator-activated receptor PPARgamma target genes. iScience 26(4):106313
abstractText  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. Female 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 PPARgamma. Collectively, we show that NLRC5 contributes to weight gain in mice, which involves transcriptional enhancement of PPARgamma targets by NLRC5 that is co-regulated by Sin3A.
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