Imperial College London
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ProfessorKevinMurphy

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Professor of Endocrinology & Metabolism
 
 
 
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Contact

 

+44 (0)20 3313 2156k.g.murphy Website

 
 
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Location

 

6N2DCommonwealth BuildingHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Hope:2022:10.1016/j.xcrm.2022.100810,
author = {Hope, D and Hinds, C and Lopes, T and Vincent, M and Shrewsbury, J and Yu, A and Davies, I and Scott, R and Jones, B and Murphy, K and Minnion, J and Sardini, A and Carling, D and Lutz, T and Bloom, S and Tan, T and Owen, B},
doi = {10.1016/j.xcrm.2022.100810},
journal = {Cell Reports Medicine},
title = {Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss},
url = {http://dx.doi.org/10.1016/j.xcrm.2022.100810},
volume = {3},
year = {2022}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Glucagon analogues show promise as components of next-generation, multi-target, anti-obesity therapeutics. The biology of chronic glucagon treatment, in particular its ability to induce energy expenditure and weight loss, remains poorly understood. Using a long-acting glucagon analogue, G108, we demonstrate that glucagon-mediated body weight loss is intrinsically linked to the hypoaminoacidemia associated with its known amino acid catabolic action. Mechanistic studies reveal an energy-consuming response to low plasma amino acids in G108-treated mice, prevented by dietary amino acid supplementation and mimicked by a rationally designed low amino acid diet. Therefore, low plasma amino acids are a prerequisite for G108-mediated energy expenditure and weight loss. However, preventing hypoaminoacidemia with additional dietary protein does not affect the ability of G108 to improve glycemia or hepatic steatosis in obese mice. These studies provide a mechanism for glucagon-mediated weight loss and confirm the hepatic glucagon receptor as an attractive molecular target for metabolic disease therapeutics.
AU  - Hope,D
AU  - Hinds,C
AU  - Lopes,T
AU  - Vincent,M
AU  - Shrewsbury,J
AU  - Yu,A
AU  - Davies,I
AU  - Scott,R
AU  - Jones,B
AU  - Murphy,K
AU  - Minnion,J
AU  - Sardini,A
AU  - Carling,D
AU  - Lutz,T
AU  - Bloom,S
AU  - Tan,T
AU  - Owen,B
DO  - 10.1016/j.xcrm.2022.100810
PY  - 2022///
SN  - 2666-3791
TI  - Hypoaminoacidemia underpins glucagon-mediated energy expenditure and weight loss
T2  - Cell Reports Medicine
UR  - http://dx.doi.org/10.1016/j.xcrm.2022.100810
UR  - http://hdl.handle.net/10044/1/101046
VL  - 3
ER  -
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