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Publication

Molecular mechanisms of snoRNA-IL-15 crosstalk in adipocyte lipolysis and NK cell rejuvenation.

Cell metabolism | 2023

Obesity, in which the functional importance of small nucleolar RNAs (snoRNAs) remains elusive, correlates with risk for many cancer types. Here, we identify that the serum copies of adipocyte-expressed SNORD46 correlate with body mass index (BMI), and serum SNORD46 antagonizes interleukin-15 (IL-15) signaling. Mechanically, SNORD46 binds IL-15 via G11, and G11A (a mutation that significantly enhances binding affinity) knockin drives obesity in mice. Functionally, SNORD46 blocks IL-15-induced, FER kinase-dependent phosphorylation of platelet glycoprotein 4 (CD36) and monoglyceride lipase (MGLL) in adipocytes, leading to inhibited lipolysis and browning. In natural killer (NK) cells, SNORD46 suppresses the IL-15-dependent autophagy, leading to reduced viability of obese NK. SNORD46 power inhibitors exhibit anti-obesity effects, concurring with improved viability of obese NK and anti-tumor immunity of CAR-NK cell therapy. Hence, our findings demonstrate the functional importance of snoRNAs in obesity and the utility of snoRNA power inhibitors for antagonizing obesity-associated immune resistance.

Pubmed ID: 37329887 RIS Download

Research resources used in this publication

None found

Additional research tools detected in this publication

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Antibodies used in this publication

Associated grants

  • Agency: NCI NIH HHS, United States
    Id: R01 CA262623
  • Agency: NCI NIH HHS, United States
    Id: P50 CA217674
  • Agency: NCI NIH HHS, United States
    Id: U54 CA274220
  • Agency: NCI NIH HHS, United States
    Id: R01 CA269646
  • Agency: NCI NIH HHS, United States
    Id: R01 CA181196
  • Agency: NCI NIH HHS, United States
    Id: R01 CA269489
  • Agency: NCI NIH HHS, United States
    Id: R01 CA255080
  • Agency: NCI NIH HHS, United States
    Id: R01 CA231011
  • Agency: NCI NIH HHS, United States
    Id: R01 CA244144
  • Agency: NCI NIH HHS, United States
    Id: R01 CA218036
  • Agency: NCI NIH HHS, United States
    Id: R01 CA247992

Publication data is provided by the National Library of Medicine ® and PubMed ®. Data is retrieved from PubMed ® on a weekly schedule. For terms and conditions see the National Library of Medicine Terms and Conditions.

This is a list of tools and resources that we have found mentioned in this publication.

PE anti-human CD314 (NKG2D) (antibody)

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APC/Cyanine7 anti-mouse CD16 (antibody)

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PE/Cyanine7 anti-mouse CD3 (antibody)

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APC anti-human CD16 (antibody)

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This monoclonal targets CD16

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APC/Cyanine7 anti-human CD56 (NCAM) (antibody)

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PE/Cyanine7 anti-human CD3 (antibody)

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Goat anti-Mouse IgG1 Cross-Adsorbed Secondary Antibody, Alexa Fluor™ 594 (antibody)

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NCAM1 (CD56) (E7X9M) XP® Rabbit mAb (antibody)

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Goat anti-Rabbit IgG (H+L) Secondary Antibody, HRP (antibody)

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Human IL-15 MAb (Clone 34559) (antibody)

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This monoclonal targets Human IL-15 MAb (Clone 34559)

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RPS8 antibody (antibody)

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This polyclonal targets RPS8

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E-Cadherin (4A2) (antibody)

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This monoclonal targets E-Cadherin

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FoxP3 (D6O8C) Rabbit mAb (antibody)

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This monoclonal targets FOXP3

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RARα (E6Z6K) Rabbit mAb (antibody)

RRID:AB_2799625

This monoclonal targets RARA

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ATF-3 (D2Y5W) Rabbit mAb (antibody)

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This monoclonal targets ATF-3

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ETV4 Monoclonal Antibody (1A2G3) (antibody)

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This monoclonal targets ETV4

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CD8α (C8/144B) Mouse mAb (IHC Specific) (antibody)

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This monoclonal targets CD8A

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PPAR alpha Monoclonal Antibody (3B6/PPAR) (antibody)

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This monoclonal targets PPAR alpha

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Estrogen Receptor α (D6R2W) Rabbit mAb #13258 (antibody)

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This monoclonal targets Estrogen Receptor alpha

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Stat4 (C46B10) Rabbit mAb (antibody)

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This monoclonal targets SOCS6

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RXR (D6H10) Rabbit mAb (antibody)

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This monoclonal targets RXR (D6H10) Rabbit mAb

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DYKDDDDK Tag (D6W5B) Rabbit mAb (Binds to same epitope as Sigma's Anti-FLAG® M2 Antibody) (antibody)

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This monoclonal targets DYKDDDDK Tag

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Mouse Anti-Human PPAR alpha Monoclonal Antibody, Unconjugated (antibody)

RRID:AB_2165759

This monoclonal targets PPARA

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Mouse Anti-Human USF2 Monoclonal, Unconjugated, Clone 5f2 (antibody)

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This monoclonal targets Human USF2

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FoxA1/HNF3α (E7E8W) Rabbit mAb (antibody)

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Stat1 (antibody)

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This monoclonal targets STAT1

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c-Fos (9F6) Rabbit mAb (antibody)

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This monoclonal targets c-Fos

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CREB (86B10) Mouse mAb (antibody)

RRID:AB_490881

This monoclonal targets CREB

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GATA-1 (D52H6) XP Rabbit mAb (antibody)

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This monoclonal targets GATA-1 (D52H6) XP Rabbit mAb

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SP1 (D4C3) Rabbit mAb (antibody)

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This monoclonal targets SP1

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Glucocorticoid Receptor (D6H2L) XP® Rabbit mAb (antibody)

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This monoclonal targets Glucocorticoid Receptor

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Vitamin D3 Receptor (D2K6W) Rabbit mAb #12550 (antibody)

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HIF-1α (D1S7W) XP® Rabbit mAb (antibody)

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This monoclonal targets HIF1A

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c-Jun (60A8) Rabbit mAb (antibody)

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XBP-1s (E9V3E) Rabbit mAb (antibody)

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This monoclonal targets XBP-1s

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Elk-1 (E-5) (antibody)

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This monoclonal targets Elk-1 (E-5)

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LXR alpha Polyclonal Antibody (antibody)

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Human/Mouse/Rat Glutathione Peroxidase 4/GPX4 Antibody (antibody)

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CD36 Polyclonal Antibody (antibody)

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Fer (5D2) Mouse mAb (antibody)

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Phospho-C/EBP beta (Thr188, Thr235) Polyclonal Antibody (antibody)

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