Glucagon-like peptide-1 receptor activation stimulates PKA-mediated phosphorylation of Raptor and this contributes to the weight loss effect of liraglutide
- Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, United States
- Department of Medicine, Vanderbilt University Medical Center, United States
Figures
Figure 1 with 2 supplements
The GLP-1R agonist liraglutide increases mTOR activity in a PKA- dependent manner (Resubmission Rev 2 Figure 1—source data 1).
(A) Immunoblot of pS6, S6, pCREB, and CREB and quantification of pS6 expression (pS6 /S6) in CHO-K1 cells transfected with the a vector expressing the hGLP1R and treated with DMSO or the mTORC1 …
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Figure 1—source data 1
Graphs of absolute quantification of data from Figure 1 and raw data in Excel spreadsheet.
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig1-data1-v2.zip
Figure 1—figure supplement 1
Absolute pS6, pCREB, and pAkt expression in CHO-K1 cells stably expressing the hGLP1R and treated with liraglutide.
(Resubmission Rev 2 Figure 1—figure supplement 1—source data 1). (A) Quantification of pS6 expression (pS6 /S6) in CHO-K1 cells transfected with the a vector expressing the hGLP1R and treated with …
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Figure 1—figure supplement 1—source data 1
Quantification of absolute values from data in Figure 1—figure supplement 1 and raw data.
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig1-figsupp1-data1-v2.zip
Figure 1—figure supplement 2
Dose response and time course of absolute pS6 and pCREB expression in CHO-K1 cells stably expressing the hGLP1R and treated with liraglutide.
(Resubmission Rev 2 Figure 1—figure supplement 2—source data 1). (A) Quantification of pS6 expression (pS6/S6) and pCREB (pCREB/CREB) in CHO-K1 cells stably expressing the hGLP1R and treated with …
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Figure 1—figure supplement 2—source data 1
Figure 1—figure supplement 2 and raw blots and raw data for Figure 1—figure supplement 2.
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig1-figsupp2-data1-v2.zip
Figure 2
PKA phosphorylates Raptor at S791 upon GLP-1R activation (Resubmission Rev 2 Figure 2—source data 1).
(A) Immunoblot and quantification of phospho-PKA substrate (pRRXS*/T*) and Myc in CHO-K1 cells stably expressing the hGLP1R transfected with Myc-wild-type (WT) Raptor or Myc-Ser791Ala Raptor and …
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Figure 2—source data 1
Figure 2, raw blots from Figure 2, and raw data for Figure 2.
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig2-data1-v2.zip
Figure 3 with 2 supplements
PKA phosphorylation of Raptor at S791 contributes to the weight-lowering effects of liraglutide in lean mice (Resubmission Rev 2 Figure 3—source data 1).
Body weight, body composition, and energy balance parameters in male wild-type (WT) and CMV-Ser791Ala Raptor knock-in (S791A) mice given vehicle (0.9% saline) or liraglutide (200 μg/kg) …
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Figure 3—source data 1
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig3-data1-v2.zip
Figure 3—figure supplement 1
Blood glucose prior to drug treatment and blood glucose and insulin post-treatment in male wild-type (WT) and Ser791Ala Raptor knock-in mice (Resubmission Rev 2 Figure 3—figure supplement 1—source data 1).
(A–D) Total (A), fat (B), lean (C), and free body fluid (D) measurements in WT and CMV-Ser791Ala Raptor mice prior to vehicle or liraglutide administration. (E– F) 5 hr fasting blood glucose in male …
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Figure 3—figure supplement 1—source data 1
Figure 3—figure supplement 1 and raw data for Figure 3—figure supplement 1.
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig3-figsupp1-data1-v2.zip
Figure 3—figure supplement 2
Generation of CMV-Ser791Ala Raptor knock-in mice.
(A) Targeting vector used by Ingenious Targeting Laboratory, Inc to introduce a Cre-inducible two base pair point mutation in an inverted exon 20 of the Raptor coding sequence. (B) Verification of …
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Figure 3—figure supplement 2—source data 1
Powerpoint slide of Figure 3—figure supplement 2.
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig3-figsupp2-data1-v2.zip
Figure 4 with 1 supplement
PKA phosphorylation of Raptor at S791 does not significantly contribute to the weight-lowering effects of liraglutide in obese mice (Resubmission Rev 2 Figure 4—source data 1).
Body weight in male wild-type (WT) and CMV-Ser791Ala Raptor knock-in (S791A) mice fed a 60% HFD for 8–10 weeks and then given vehicle (0.9% saline) or liraglutide (200 μg/kg) subcutaneously twice a …
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Figure 4—source data 1
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig4-data1-v2.zip
Figure 4—figure supplement 1
Relationship between baseline body weight and liraglutide-induced weight loss in male wild-type (WT) and Ser791Ala Raptor knock-in mice (Resubmission Rev 2 Figure 4—figure supplement 1—source data 1).
(A) Relationship between baseline body weight and liraglutide-induced weight loss in HFD-fed wild-type (WT) and CMV-Ser791Ala Raptor knock-in (S791A) mice (Test if slopes are non-zero: WT, F (1,10) …
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Figure 4—figure supplement 1—source data 1
Figure 4—figure supplement 1 and its raw data for Figure 4—figure supplement 1.
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig4-figsupp1-data1-v2.zip
Figure 5
PKA phosphorylation of Raptor at S791 is not required for the weight-lowering effect of setmelanotide (Resubmission Rev 2 Figure 5—source data 1).
Body weight and body composition in male wild-type (WT) and CMV-Ser791Ala Raptor knock-in (S791A) mice given vehicle (0.9% saline) or setmelanotide (4 mg/kg) subcutaneously once a day for 9 days. …
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Figure 5—source data 1
- https://cdn.elifesciences.org/articles/80944/elife-80944-fig5-data1-v2.zip
Author response image 1
