Evidence map›Paper›PMID 31484069›Full record

ArticleCell reports2019

Peptide/Receptor Co-evolution Explains the Lipolytic Function of the Neuropeptide TLQP-21.

Bhavani S Sahu, Pedro Rodriguez, Megin E Nguyen, Ruijun Han, Cheryl Cero, Maria Razzoli, Paolo Piaggi, Lauren J Laskowski, Mihaela Pavlicev, Louis Muglia and 6 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Cell reports, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.

0numbers the graph read from it
0cells of the map it votes in
15citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

15 citing papers in PubMed.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Article
  6. Article
  7. Article
  8. Review
  9. The molecular identity of the TLQP-21 peptide receptor.Cellular and molecular life sciences : CMLS · 2021
    Review
  10. Article
  11. Article
  12. Article
  13. Stress and Alzheimer's disease: A senescence link?Neuroscience and biobehavioral reviews · 2020
    Review
  14. Article
  15. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

16 authors.

Bhavani S SahuDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA.
Pedro RodriguezDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA.
Megin E NguyenDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA.
Ruijun HanDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA.
Cheryl CeroDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA.
Maria RazzoliDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA.
Paolo PiaggiPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Phoenix, AZ, USA.
Lauren J LaskowskiDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Mihaela PavlicevDivision of Human Genetics, Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Louis MugliaDivision of Human Genetics, Center for Prevention of Preterm Birth, Perinatal Institute, Cincinnati Children's Hospital Medical Center, Cincinnati, OH, USA; Department of Pediatrics, University of Cincinnati College of Medicine, Cincinnati, OH, USA.
Sushil K MahataVA San Diego Healthcare System, San Diego, CA, USA; Department of Medicine, University of California at San Diego, La Jolla, CA, USA.
Scott O'GradyDepartment of Animal Science, University of Minnesota, 480 Haecker Hall, 1364 Eckles Avenue, St. Paul, MN, USA.
John D McCorvyDepartment of Cell Biology, Neurobiology and Anatomy, Medical College of Wisconsin, Milwaukee, WI 53226, USA.
Leslie J BaierPhoenix Epidemiology and Clinical Research Branch, National Institute of Diabetes, Digestive and Kidney Diseases, NIH, Phoenix, AZ, USA.
Yuk Y ShamDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA; Bioinformatics and Computational Biology Program, University of Minnesota, Minneapolis, MN, USA.
Alessandro BartolomucciDepartment of Integrative Biology and Physiology, University of Minnesota, 2231 6(th) St. SE, Minneapolis, MN, USA. Electronic address: abartolo@umn.edu.

Funding

Mechanisms of IL-33 secretion in allergic diseasesR01AI128729 · NIAID · MAYO CLINIC ROCHESTER · PI Hirohito Kita, SCOTT M. O'GRADY · 2017 to 2026
$5.6M
Neural mechanisms for VGF regulation of energy balanceR01DK117504 · NIDDK · ICAHN SCHOOL OF MEDICINE AT MOUNT SINAI · PI BARTOLOMUCCI, ALESSANDRO, BUETTNER, CHRISTOPH · 2018 to 2021
$2.7M
Molecular dissection of TLQP-21 peptide functions in obesityR01DK102496 · NIDDK · UNIVERSITY OF MINNESOTA · PI BARTOLOMUCCI, ALESSANDRO · 2014 to 2018
$1.7M
BLRD VA I01 BX000323NIAID NIH HHS R01 AI128729NIDDK NIH HHS R01 DK102496NIDDK NIH HHS R01 DK117504
6 · The paper itself

Abstract

Structural and functional diversity of peptides and GPCR result from long evolutionary processes. Even small changes in sequence can alter receptor activation, affecting therapeutic efficacy. We conducted a structure-function relationship study on the neuropeptide TLQP-21, a promising target for obesity, and its complement 3a receptor (C3aR1). After having characterized the TLQP-21/C3aR1 lipolytic mechanism, a homology modeling and molecular dynamics simulation identified the TLQP-21 binding motif and C3aR1 binding site for the human (h) and mouse (m) molecules. mTLQP-21 showed enhanced binding affinity and potency for hC3aR1 compared with hTLQP-21. Consistently, mTLQP-21, but not hTLQP-21, potentiates lipolysis in human adipocytes. These findings led us to uncover five mutations in the C3aR1 binding pocket of the rodent Murinae subfamily that are causal for enhanced calculated affinity and measured potency of TLQP-21. Identifying functionally relevant peptide/receptor co-evolution mechanisms can facilitate the development of innovative pharmacotherapies for obesity and other diseases implicating GPCRs.

Indexed as

Evolution, MolecularLipolysis3T3-L1 CellsAdipocytesAdipose Tissue, WhiteAdrenergic AgentsAdultAmino Acid MotifsAnimalsCalciumComputer SimulationExtracellular SpaceHumansMaleMiceMice, Inbred C57BLAdrenergic AgentsCalciumcomplement C3a receptorNeuropeptidesPeptide FragmentsReceptors, ComplementTLQP-21 peptidedrug discoverygranin peptidesinnate immunitylipolytic catecholamine resistanceobesitytransient receptor potential channelVGF

Identifiers

PMID31484069
PMCPMC6753381

What Socratic holds

Textmetadata
LicenceCC BY-NC-ND
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.