Evidence map›Paper›PMID 38796310›Full record

ArticleMolecular metabolism2024

The novel adrenergic agonist ATR-127 targets skeletal muscle and brown adipose tissue to tackle diabesity and steatohepatitis.

Emanuela Talamonti, Jelena Davegardh, Anastasia Kalinovich, Sten M M van Beek, Nodi Dehvari, Carina Halleskog, Hamza M Bokhari, Dana S Hutchinson, Seungmin Ham, Laura J Humphrys and 21 more

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Article in Molecular metabolism, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.

0numbers the graph read from it
0cells of the map it votes in
4citing 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

4 citing papers in PubMed.

  1. Trial
  2. Article
  3. Review
  4. Article
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

31 authors.

Emanuela TalamontiAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Jelena DavegardhDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden.
Anastasia KalinovichAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Sten M M van BeekAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Nodi DehvariAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Carina HalleskogAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Hamza M BokhariAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Dana S HutchinsonDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Seungmin HamDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Laura J HumphrysSchool of Life Sciences, The Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Nicola C DijonSchool of Life Sciences, The Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, UK.
Aikaterini MotsoDepartment of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden; Karolinska Institutet, Department of Physiology and Pharmacology, Stockholm, Sweden.
Anna SandstromAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Evelyn ZacharewiczDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
Ilga MutuleLatvian Institute of Organic Synthesis, Riga, Latvia.
Edgars SunaLatvian Institute of Organic Synthesis, Riga, Latvia.
Jana SpuraLatvian Institute of Organic Synthesis, Riga, Latvia.
Karolina DitrychovaNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Righospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Leigh A StoddartExcellerate Bioscience, The Triangle, NG2 Business Park, Nottingham, UK.
Nicholas D HollidaySchool of Life Sciences, The Medical School, Queen's Medical Centre, University of Nottingham, Nottingham, UK; Excellerate Bioscience, The Triangle, NG2 Business Park, Nottingham, UK.
Shane C WrightKarolinska Institutet, Department of Physiology and Pharmacology, Stockholm, Sweden.
Volker M LauschkeKarolinska Institutet, Department of Physiology and Pharmacology, Stockholm, Sweden; Dr. Margarete Fischer-Bosch Institute of Clinical Pharmacology, Stuttgart, Germany; Tübingen University, Tübingen, Germany.
Soren NielsenNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Righospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Camilla ScheeleNovo Nordisk Foundation Center for Basic Metabolic Research, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen, Denmark; The Centre of Inflammation and Metabolism and Centre for Physical Activity Research, Righospitalet, University Hospital of Copenhagen, Copenhagen, Denmark.
Elizabeth CheesmanCardio-Vascular Molecular & Therapeutics Translational Research Group, Northside Clinical School of Medicine, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia.
Joris HoeksDepartment of Nutrition and Movement Sciences, NUTRIM School of Nutrition and Translational Research in Metabolism, Maastricht University Medical Center, Maastricht, the Netherlands.
Peter MolenaarCardio-Vascular Molecular & Therapeutics Translational Research Group, Northside Clinical School of Medicine, Faculty of Medicine, University of Queensland, Brisbane, Queensland, Australia; Queensland University of Technology (QUT), School of Biomedical Sciences, Institute of Health and Biomedical Innovation, 60 Musk Avenue, Kelvin Grove, Queensland, Australia.
Roger J SummersDrug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, Victoria, Australia.
Benjamin PelcmanAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden.
Gopala K YakalaAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden. Electronic address: gopala@atrogi.com.
Tore BengtssonAtrogi AB, Tomtebodavagen 6, Solna, Stockholm, Sweden; Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, Stockholm, Sweden. Electronic address: tore.bengtsson@su.se.

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

objectiveSimultaneous activation of β2- and β3-adrenoceptors (ARs) improves whole-body metabolism via beneficial effects in skeletal muscle and brown adipose tissue (BAT). Nevertheless, high-efficacy agonists simultaneously targeting these receptors whilst limiting activation of β1-ARs - and thus inducing cardiovascular complications - are currently non-existent. Therefore, we here developed and evaluated the therapeutic potential of a novel β2-and β3-AR, named ATR-127, for the treatment of obesity and its associated metabolic perturbations in preclinical models.

methodsIn the developmental phase, we assessed the impact of ATR-127's on cAMP accumulation in relation to the non-selective β-AR agonist isoprenaline across various rodent β-AR subtypes, including neonatal rat cardiomyocytes. Following these experiments, L6 muscle cells were stimulated with ATR-127 to assess the impact on GLUT4-mediated glucose uptake and intramyocellular cAMP accumulation. Additionally, in vitro, and in vivo assessments are conducted to measure ATR-127's effects on BAT glucose uptake and thermogenesis. Finally, diet-induced obese mice were treated with 5 mg/kg ATR-127 for 21 days to investigate the effects on glucose homeostasis, body weight, fat mass, skeletal muscle glucose uptake, BAT thermogenesis and hepatic steatosis.

resultsExposure of L6 muscle cells to ATR-127 robustly enhanced GLUT4-mediated glucose uptake despite low intramyocellular cAMP accumulation. Similarly, ATR-127 markedly increased BAT glucose uptake and thermogenesis both in vitro and in vivo. Prolonged treatment of diet-induced obese mice with ATR-127 dramatically improved glucose homeostasis, an effect accompanied by decreases in body weight and fat mass. These effects were paralleled by an enhanced skeletal muscle glucose uptake, BAT thermogenesis, and improvements in hepatic steatosis.

conclusionsOur results demonstrate that ATR-127 is a highly effective, novel β2- and β3-ARs agonist holding great therapeutic promise for the treatment of obesity and its comorbidities, whilst potentially limiting cardiovascular complications. As such, the therapeutic effects of ATR-127 should be investigated in more detail in clinical studies.

Indexed as

Adipose Tissue, BrownMice, Inbred C57BLMuscle, SkeletalAdrenergic AgonistsAnimalsFatty LiverMaleMiceObesityRatsThermogenesisAdrenergic AgonistsHepatic steatosisObesitySkeletal muscleType 2 diabetesβ-Adrenergic agonists

Identifiers

PMID38796310
PMCPMC11258667

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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 OpenQuestion graph.