NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program

Hiraike, Yuta; Waki, Hironori; Yu, Jing; Nakamura, Masahiro; Miyake, Kana; Nagano, Gaku; Nakaki, Ryo; Suzuki, Ken; Kobayashi, Hirofumi; Yamamoto, Shozo; Sun, Wei; Aoyama, Tomohisa; Hirota, Yoshikazu; Ohno, Haruya; Oki, Kenji; Yoneda, Masayasu; White, A.; Tseng, Yu‐Hua; Cypess, Aaron M.; Larsen, Therese Juhlin; Jespersen, Naja Zenius; Schéele, Camilla; Tsutsumi, Sadami; Aburatani, Hiroyuki; Yamauchi, Toshimasa; Kadowaki, Takashi

doi:10.1038/ncb3590

Cited by 80 publications

(95 citation statements)

References 52 publications

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“…PPARc can be induced before transcription activation of adipocyte genes and plays an important role in adipocyte differentiation [64]. PPARc localizes at the brown-fat-specific enhancers, and the binding of nuclear factor I-A (NFIA) to the brown fat enhancers precedes and facilitates the binding of PPARc, leading to increased chromatin accessibility and active transcription [65]. PPARc can also regulate the mutual transformation between adipocytes and osteoblasts, thereby affecting lipid metabolism, which can promote the differentiation of bone marrow mesenchymal stem cells into adipocytes and inhibit the differentiation into osteoblasts [66].…”

Section: Pparγ In Renal Lipid Metabolismmentioning

confidence: 99%

PPARγ and Its Agonists in Chronic Kidney Disease

Shi

Wang

et al. 2020

International Journal of Nephrology

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Chronic kidney disease (CKD) has become a global healthcare issue. CKD can progress to irreversible end-stage renal diseases (ESRD) or renal failure. e major risk factors for CKD include obesity, diabetes, and cardiovascular diseases. Understanding the key process involved in the disease development may lead to novel interventive strategies, which is currently lagging behind. Peroxisome proliferator-activated receptor c (PPARc) is one of the ligand-activated transcription factor superfamily members and is globally expressed in human tissues. Its agonists such as thiazolidinediones (TZDs) have been applied as effective antidiabetic drugs as they control insulin sensitivity in multiple metabolic tissues. Besides, TZDs exert protective effects in multiple other CKD risk disease contexts. As PPARc is abundantly expressed in major kidney cells, its physiological roles in those cells have been studied in both cell and animal models. e function of PPARc in the kidney ranges from energy metabolism, cell proliferation to inflammatory suppression, although major renal side effects of existing agonists (including TZDs) have been reported, which limited their application in treating CKD. In the current review, we systemically assess the function of PPARc in CKDs and the benefits and current limitations of its agonists in the clinical applications.

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Section: Pparγ In Renal Lipid Metabolismmentioning

confidence: 99%

PPARγ and Its Agonists in Chronic Kidney Disease

Shi

Wang

et al. 2020

International Journal of Nephrology

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“…Interestingly, we find a small set of 6-mers with higher weights that classify humandecrease and chimpanzee-increase OCRs, which correspond to NFI binding motifs (Supplemental Table 11). This result is intriguing since NFIA and the master adipogenesis transcription factor PPARG co-localize to regulate adipogenesis in brown adipocytes as well as in white adipocytes transdifferentiating into beige adipocytes (24,25). Since co-localization of NFIA and PPARG motifs is correlated with an increase in brown adipocyte gene expression, we could measure how often NFIA and PPARG binding motifs occur in the same OCR ( Figure 4B).…”

Section: Transcription Factor Binding Motifs Characterize Species-spementioning

confidence: 99%

“…Although histology on frozen adipose samples is challenging, we can still observe evidence of browning from the chromatin landscape. The NFI motif has been implicated in adipogenesis and differences in brown and white tissues (24,25). A recent systems biology comparison of murine brown and white adipose found that open chromatin regions enriched in brown adipose contain the NFI motif and a high enrichment for GO terms involved with browning of fat (24).…”

Section: Humans May Have Lower Beiging Potential Than Chimpanzeesmentioning

confidence: 99%

Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates

Swain-Lenz

Berrío

Safi

et al. 2019

Preprint

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Humans carry a much larger percentage of body fat than other primates. Despite the central role of adipose tissue in metabolism, little is known about the evolution of white adipose tissue in primates. Phenotypic divergence is often caused by genetic divergence in cis-regulatory regions. We examined the cis-regulatory landscape of fat during human origins by performing comparative analyses of chromatin accessibility in human and chimpanzee adipose tissue using macaque as an outgroup. We find that many cis-regulatory regions that are specifically closed in humans are under positive selection, located near genes involved with lipid metabolism, and contain a short sequence motif involved in the beigeing of fat, the process in which white adipocytes are transdifferentiated into beige adipocytes. While the primary role of white adipocytes is to store lipids, beige adipocytes are thermogeneic. The collective closing of many putative regulatory regions associated with beiging of fat suggests an adaptive mechanism that increases body fat in humans.

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“…PCSK5 has also been identified as a putative gene associated with feed utilization efficiency, in part owing to its differential expression in the liver of divergent residual feed intake animals (Tizioto et al 2015). NFIA (nuclear factor I-A) is associated with regulating brown adipose tissue gene expression patterns (Hiraike et al 2017;Shapira & Seale 2017), and regulates the differentiation of embryonic articular cartilage (Singh et al 2018).…”

mentioning

confidence: 99%

Identification of genetic loci associated with growth traits at weaning in yak through a genome‐wide association study

Jia

et al. 2019

Animal Genetics

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Summary A multilocus GWAS was performed to explore the genetic architecture of four growth traits in yak. In total, 354 female yaks for which measurements of body weight (BW), withers height (WH), body length (BL) and chest girth (CG) at weaning were available underwent genotyping with the Illumina BovineHD BeadChip (770K). After quality control, we retained 98 688 SNPs and 354 animals for GWAS analysis. We identified seven, 18, seven and nine SNPs (corresponding to seven, 17, seven and eight candidate genes) associated with BW, WH, BL and CG at weaning respectively. Interestingly, most of these candidate genes were reported to be involved in growth‐related processes such as muscle formation, lipid deposition, feed efficiency, carcass composition and development of the central and peripheral nervous system. Our results offer novel insight into the molecular architecture underpinning yak growth traits. Further functional analyses are thus warranted to explore the molecular mechanisms whereby these genes affect these traits of interest.

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NFIA co-localizes with PPARγ and transcriptionally controls the brown fat gene program

Cited by 80 publications

References 52 publications

PPARγ and Its Agonists in Chronic Kidney Disease

PPARγ and Its Agonists in Chronic Kidney Disease

Comparative analyses of chromatin landscape in white adipose tissue suggest humans may have less beigeing potential than other primates

Identification of genetic loci associated with growth traits at weaning in yak through a genome‐wide association study

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