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Study · Animal study (in vivo) · mouse · 2023

7 results

Glucagon-like peptide-1 receptor activation stimulates PKA-mediated phosphorylation of Raptor and this contributes to the weight loss effect of liraglutide.

Le TDV, Liu D, Besing GK, Raghavan R, Ellis BJ, Ceddia RP, Collins S, Ayala JE

eLife6 Nov 2023Cited by 10 (Europe PMC)

PMID37930356 (opens in a new tab)PMCIDPMC10691799 (opens in a new tab)DOI10.7554/elife.80944 (opens in a new tab)PepBankPUB-37930356
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Summary

The canonical target of the glucagon-like peptide-1 receptor (GLP-1R), Protein Kinase A (PKA), has been shown to stimulate mechanistic Target of Rapamycin Complex 1 (mTORC1) by phosphorylating the mTOR-regulating protein Raptor at Ser791 following β-adrenergic stimulation. The objective of these studies is to test whether GLP-1R agonists similarly stimulate mTORC1 via PKA phosphorylation of Raptor at Ser791 and whether this contributes to the weight loss effect of the therapeutic GLP-1R agonist liraglutide. We measured phosphorylation of the mTORC1 signaling target ribosomal protein S6 in Chinese Hamster Ovary cells expressing GLP-1R (CHO-Glp1r) treated with liraglutide in combination with PKA inhibitors. We also assessed liraglutide-mediated phosphorylation of the PKA substrate RRXS*/T* motif in CHO-Glp1r cells expressing Myc-tagged wild-type (WT) Raptor or a PKA-resistant (Ser791Ala) Raptor mutant. Finally, we measured the body weight response to liraglutide in WT mice and mice with a targeted knock-in of PKA-resistant Ser791Ala Raptor. Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser791Ala Raptor in CHO-Glp1r cells. Lean Ser791Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss but not setmelanotide-induced (melanocortin-4 receptor-dependent) weight loss. Diet-induced obese Ser791Ala Raptor knock-in mice were not resistant to liraglutide-induced weight loss; however, there was weight-dependent variation such that there was a tendency for obese Ser791Ala Raptor knock-in mice of lower relative body weight to be resistant to liraglutide-induced weight loss compared to weight-matched controls. Together, these findings suggest that PKA-mediated phosphorylation of Raptor at Ser791 contributes to liraglutide-induced weight loss.
CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study7

7 results from studies that gave the peptide. No result from this study comes from people.

  1. 01AnimalAnimal study (in vivo)Efficacy outcome

    Lean Ser791Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss compared with WT mice.

    In plain wordsIn lean mutant mice, liraglutide produced less weight loss than in normal mice.

    Peptide
    Liraglutide
    Outcome
    DecreaseWeight loss in lean knock-in mice
    Study

    mousen: not reported in source

    Lean Ser791Ala Raptor knock-in mice
    Comparator
    WT mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Lean Ser791Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss but not setmelanotide-induced (melanocortin-4 receptor-dependent) weight loss.
    1 context sentence
    Summary · context
    Finally, we measured the body weight response to liraglutide in WT mice and mice with a targeted knock-in of PKA-resistant Ser791Ala Raptor.
  2. 02AnimalAnimal study (in vivo)Efficacy outcome

    In lean Ser791Ala Raptor knock-in mice, setmelanotide induced weight loss without resistance.

    In plain wordsIn lean mutant mice, setmelanotide induced weight loss without resistance.

    Peptide
    Setmelanotide
    Outcome
    DecreaseWeight loss in lean knock-in mice
    Study

    mousen: not reported in source

    Lean Ser791Ala Raptor knock-in mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Lean Ser791Ala Raptor knock-in mice were resistant to liraglutide-induced weight loss but not setmelanotide-induced (melanocortin-4 receptor-dependent) weight loss.
  3. 03AnimalAnimal study (in vivo)Efficacy outcome

    In diet-induced obese Ser791Ala Raptor knock-in mice, liraglutide induced weight loss without overall resistance.

    In plain wordsIn obese mutant mice, liraglutide induced weight loss without overall resistance.

    Peptide
    Liraglutide
    Outcome
    DecreaseWeight loss in obese knock-in mice
    Study

    mousen: not reported in source

    Diet-induced obese Ser791Ala Raptor knock-in mice
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Diet-induced obese Ser791Ala Raptor knock-in mice were not resistant to liraglutide-induced weight loss;
  4. 04AnimalAnimal study (in vivo)Efficacy outcome

    In lower-weight obese Ser791Ala Raptor knock-in mice, liraglutide showed a tendency toward reduced weight-loss response versus weight-matched controls.

    In plain wordsIn lower-weight obese mutant mice, liraglutide tended to produce less weight loss than in weight-matched controls.

    Peptide
    Liraglutide
    Outcome
    DecreaseWeight-dependent resistance to weight loss
    Study

    mousen: not reported in source

    Lower-weight diet-induced obese Ser791Ala Raptor knock-in mice
    Comparator
    Weight-matched controls
    Outcome group
    Body weight · Metabolic and weight
    Studied dose
    Dose not stated

    Source sentences

    Summary
    however, there was weight-dependent variation such that there was a tendency for obese Ser791Ala Raptor knock-in mice of lower relative body weight to be resistant to liraglutide-induced weight loss compared to weight-matched controls.
  5. 05LabIn vitro (cells)Mechanism

    In CHO-Glp1r cells, liraglutide increased S6 phosphorylation in a PKA-dependent manner.

    In plain wordsIn cells, liraglutide increased S6 phosphorylation through a PKA-dependent process.

    Peptide
    Liraglutide
    Outcome
    IncreaseS6 phosphorylation
    Study

    Chinese hamstern: not reported in source

    CHO-Glp1r cells expressing WT Raptor
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser791Ala Raptor in CHO-Glp1r cells.
  6. 06LabIn vitro (cells)Mechanism

    In CHO-Glp1r cells, liraglutide increased WT Raptor PKA motif phosphorylation in a PKA-dependent manner.

    In plain wordsIn cells, liraglutide increased phosphorylation of the PKA motif in normal Raptor.

    Peptide
    Liraglutide
    Outcome
    IncreaseWT Raptor PKA motif phosphorylation
    Study

    Chinese hamstern: not reported in source

    CHO-Glp1r cells expressing WT Raptor
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser791Ala Raptor in CHO-Glp1r cells.
  7. 07LabIn vitro (cells)Mechanism

    In CHO-Glp1r cells, liraglutide failed to stimulate PKA motif phosphorylation in Ser791Ala Raptor.

    In plain wordsIn cells, liraglutide did not stimulate PKA motif phosphorylation in mutant Raptor.

    Peptide
    Liraglutide
    Outcome
    No significant changeMutant Raptor PKA motif phosphorylation
    Study

    Chinese hamstern: not reported in source

    CHO-Glp1r cells expressing Ser791Ala Raptor
    Outcome group
    Receptor activity and mechanism · Pharmacology
    Studied dose
    Dose not stated

    Source sentences

    Summary
    Liraglutide increased phosphorylation of S6 and the PKA motif in WT Raptor in a PKA-dependent manner but failed to stimulate phosphorylation of the PKA motif in Ser791Ala Raptor in CHO-Glp1r cells.

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

  1. Version 3Current

    28 Oct 2026, 02:03 UTC

    Study results updated

  2. Version 2

    27 Oct 2026, 16:36 UTC

    Study data updated · source update from Europe PMC

  3. Version 1

    9 Oct 2026, 03:05 UTC

    First added · source update from Europe PMC

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