Deficiency of peroxisomal NUDT7 stimulates de novo lipogenesis in hepatocytes

Song, Jinping; Baek, In-Jeoung; Park, Sujeong; Oh, Jinjoo; Kim, Deokha; Song, Kyung; Kim, Mi Kyung; Lee, Hye Won; Jang, Byoung Kuk; Jin, Eun‐Jung

doi:10.1016/j.isci.2022.105135

Cited by 5 publications

(6 citation statements)

References 53 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The origin protein of peptide MLL3 (3019-3045) regulates metabolic processes and the hepatic circadian control of bile acid homeostasis 32 . MLL3 is involved in fatty liver development 33 and the non-alcoholic fatty liver disease (NAFLD) pathology by methylation of histone 3 forming H3K4me3, which interacts with the promoters of PPARγ resulting in increased de novo lipogenesis in hepatocytes leading to NAFLD 34 .…”

Section: Discussionmentioning

confidence: 99%

Alterations of the peptidomic composition of peripheral plasma after portal hypertension correction by transjugular intrahepatic portosystemic shunt

Bagarolo,

Bhargava,

Schierwagen

et al. 2024

Preprint

View full text Add to dashboard Cite

Portal-hypertension develops in patients with advanced chronic liver diseases(CLD), especially cirrhosis and is associated with complications, such as gastrointestinal bleeding and ascites resulting in high mortality. The transjugular intrahepatic portosystemic shunt(TIPS) is a treatment option for portal-hypertension, aiming to decrease portal venous pressure by establishing an artificial passage for blood from the gastrointestinal tract to the liver vein. This study focuses on the differences in the molecular composition of plasma samples from patients with portal-hypertension before and after TIPS intervention to identify and characterise mediators influencing gut-liver cross-talk. The plasma of 23 patients suffering from advanced CLD with portal-hypertension was collected from peripheral veins before and after TIPS treatment and analysed using a well-established non-targeted chromatography-mass spectrometric(LC-MS) approach. Sialomucin core protein 24(CD164)(160–180), meckelin(99–118), Histone-lysine N-methyltransferase(MLL3)(3019–3045) and transient receptor potential cation channel subfamily V member 5(TRPV5)(614–630) were identified to be downregulated after the TIPS treatment. In addition, the metabolites 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid(CMPF), uric acid, Dopamine, homoarginine, leucylproline and 5-methyluridine were significantly decreased after TIPS, whereas one yet unidentified low molecular-weight metabolite showed an increase after the medical procedure. In conclusion, these substances are novel biomarkers for portal-hypertension in patients with CLD, with mechanistic clues of involvement in regulating pathological gut-liver cross-talk.

show abstract

Section: Discussionmentioning

confidence: 99%

Alterations of the peptidomic composition of peripheral plasma after portal hypertension correction by transjugular intrahepatic portosystemic shunt

Bagarolo,

Bhargava,

Schierwagen

et al. 2024

Preprint

View full text Add to dashboard Cite

show abstract

“…reported that their independently generated, chow-fed Nudt7 +/- and Nudt7 -/- mice accumulated triacylglycerols in the liver. The Nudt7 +/ - mice also contained a higher hepatic content of palmitate and elevated transcript levels of PPARγ target genes such as Cd36 , Fabp4 , and Il6 ( 89 ). While we did not observe any of these changes, the animals we studied were significantly younger than the 12 month-old Nudt7 +/- and Nudt7 -/- mice described by Song J. et al.…”

Section: Discussionmentioning

confidence: 99%

NUDT7 regulates total hepatic CoA levels and the composition of the intestinal bile acid pool in male mice fed a Western diet

Vickers

Shumar²,

Saporito³

et al. 2023

Journal of Biological Chemistry

View full text Add to dashboard Cite

“…We found that the expression of Pparɑ, Cyp4a12a/b, Acaa1a, Nudt7 and Pex11ɑ was up-regulated in RBP-J knockout group. Interestingly, these genes, which are regulated by Pparɑ, are closely related to peroxisomal fatty acid oxidation and fatty acid degradation [27][28][29][30][31][32][33][34]. Naturally, we speculated that macrophage RBP-J knockout can attenuate the expression of TNFɑ and IL1β, then the reduced TNFɑ and IL1β may enhance the expression or activity of Pparɑ in hepatocytes, up-regulate the expression of Cyp4a12a/b, Acaa1a and Pex11ɑ, promote peroxisomal fatty acids oxidation and fatty acid degradation, and finally reduce lipid accumulation in hepatocytes.…”

Section: Discussionmentioning

confidence: 99%

“…S6C). Studies have shown that Cyp4a12a/b is associated with fatty acid degradation [27,28], and Acaa1a, Nudt7, Pex11a are related to peroxisomal fatty acid oxidation [29][30][31][32][33][34]. Pparɑ could regulate the expression of Cyp4a12a/b, Acaa1a and Pex11ɑ [27][28][29][30]34].…”

Section: Myeloid-specific Rbp-j Deficiency Up-regulated the Expressio...mentioning

confidence: 99%

See 1 more Smart Citation

Myeloid-specific blockade of Notch signaling ameliorates nonalcoholic fatty liver disease in mice

Ding¹,

Xu²,

Du³

et al. 2023

Int. J. Biol. Sci.

View full text Add to dashboard Cite

Rationale: Macrophages play a central role in the development and progression of nonalcoholic fatty liver disease (NAFLD). Studies have shown that Notch signaling mediated by transcription factor recombination signal binding protein for immunoglobulin kappa J region (RBP-J), is implicated in macrophage activation and plasticity. Naturally, we asked whether Notch signaling in macrophages plays a role in NAFLD, whether regulating Notch signaling in macrophages could serve as a therapeutic strategy to treat NAFLD. Methods: Immunofluorescence staining was used to detect the changes of macrophage Notch signaling in the livers of human patients with NAFLD and choline deficient amino acid-defined (CDAA) diet-fed mice. Lyz2-Cre RBP-J flox or wild-type C57BL/6 male mice were fed with CDAA or high fat diet (HFD) to induce experimental steatohepatitis or steatosis, respectively. Liver histology examinations were performed using hematoxylin-eosin (H&E), Oil Red O staining, Sirius red staining and immunohistochemistry staining for F4/80, Col1α1 and αSMA. The expression of inflammatory factors, fibrosis or lipid metabolism associated genes were evaluated by quantitative reverse transcription (qRT)-PCR, Western blot or enzyme-linked immunosorbent assay (ELISA). The mRNA expression of liver samples was profiled by using RNA-seq. A hairpin-type decoy oligodeoxynucleotides (ODNs) for transcription factor RBP-J was loaded into bEnd.3-derived exosomes by electroporating. Mice with experimental NAFLD were treated with exosomes loading RBP-J decoy ODNs via tail vein injection. In vivo distribution of exosomes was analyzed by fluorescence labeling and imaging. Results: The results showed that Notch signaling was activated in hepatic macrophages in human with NAFLD or in CDAA-fed mice. Myeloid-specific RBP-J deficiency decreased the expression of inflammatory factors interleukin-1 beta (IL1β) and tumor necrosis factor alpha (TNFα), attenuated experimental steatohepatitis in mice. Furthermore, we found that Notch blockade attenuated lipid accumulation in hepatocytes by inhibiting the expression of IL1β and TNFα in macrophages in vitro . Meanwhile, we observed that tail vein-injected exosomes were mainly taken up by hepatic macrophages in mice with steatohepatitis. RBP-J decoy ODNs delivered by exosomes could efficiently inhibit Notch signaling in hepatic macrophages in vivo and ameliorate steatohepatitis or steatosis in CDAA or HFD mice, respectively. Conclusions: Combined, macrophage RBP-J promotes the progression of NAFLD at least partially through regulating the expression of pro-inflammatory cytokines IL1β and TNFα. Infusion of exosomes loaded with RBP-J decoy ODNs might be a promising therapy to treat NAFLD.

show abstract

Deficiency of peroxisomal NUDT7 stimulates de novo lipogenesis in hepatocytes

Cited by 5 publications

References 53 publications

Alterations of the peptidomic composition of peripheral plasma after portal hypertension correction by transjugular intrahepatic portosystemic shunt

Alterations of the peptidomic composition of peripheral plasma after portal hypertension correction by transjugular intrahepatic portosystemic shunt

NUDT7 regulates total hepatic CoA levels and the composition of the intestinal bile acid pool in male mice fed a Western diet

Myeloid-specific blockade of Notch signaling ameliorates nonalcoholic fatty liver disease in mice

Contact Info

Product

Resources

About