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{Izzi-Engbeaya:2020:10.1016/j.molmet.2020.02.015,
author = {Izzi-Engbeaya, C and Ma, Y and Buckley, NW and Ratnasabapathy, R and Richardson, E and Counsell, JR and Fernandes-Freitas, I and Norton, M and Farooq, G and Mirza, Z and Cai, M and Cheetham, S and Seckl, J and Murphy, K and Dhillo, WS and Gardiner, J},
doi = {10.1016/j.molmet.2020.02.015},
journal = {Molecular Metabolism},
pages = {1--7},
title = {Effects of corticosterone within the hypothalamic arcuate nucleus on food intake and body weight in male rats},
url = {http://dx.doi.org/10.1016/j.molmet.2020.02.015},
volume = {36},
year = {2020}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BackgroundObesity is a major cause of morbidity and mortality. Few weight-reducing medications are available, and these have limited efficacy. Cushing’s Syndrome (caused by elevated glucocorticoid levels) and obesity have similar metabolic features. Though circulating glucocorticoid levels are not elevated in obesity, tissue-specific glucocorticoid levels have been implicated in the development of the metabolic phenotype of obesity. Tissue glucocorticoid levels are regulated by 11β-hydroxysteroid dehydrogenase type1 (11βHSD1), which increases the local concentration of active glucocorticoids by production of corticosterone from 11-dehydrocorticosterone. 11βHSD1 is expressed in the hypothalamic arcuate nucleus (ARC), a major weight and appetite-regulating centre, and therefore represents a target for novel anti-obesity therapeutic agents.ObjectivesTo investigate the effect of chronic alterations of ARC corticosterone levels (mediated by 11βHSD1) on food intake and body weight in adult male rats.MethodsRecombinant adeno-associated virus bearing sense 11βHSD1 (rAAV-S11βHSD1) and small interfering 11βHSD1 (rAAV-si11βHSD1) respectively were stereotactically injected into the ARC (bilaterally) of adult male Wistar rats. rAAV-GFP was injected into control groups of male Wistar rats. Food intake and body weight were measured three times a week for 70 days. Terminal brain, plasma and intrascapular brown adipose tissue (iBAT) samples were taken for measurement of mRNA expression and hormone levels.ResultsCompared to controls, rAAV-S11βHSD1 injection resulted in higher ARC corticosterone levels, hyperphagia and increased weight gain. Conversely, rAAV-si11βHSD1 injection (compared to controls) resulted in lower ARC corticosterone levels, higher iBAT uncoupling protein-1 mRNA expression and less weight gain despite similar food intake.ConclusionsTherefore, ARC corticosterone, regulated by 11βHSD1, may play a role in fo
AU  - Izzi-Engbeaya,C
AU  - Ma,Y
AU  - Buckley,NW
AU  - Ratnasabapathy,R
AU  - Richardson,E
AU  - Counsell,JR
AU  - Fernandes-Freitas,I
AU  - Norton,M
AU  - Farooq,G
AU  - Mirza,Z
AU  - Cai,M
AU  - Cheetham,S
AU  - Seckl,J
AU  - Murphy,K
AU  - Dhillo,WS
AU  - Gardiner,J
DO  - 10.1016/j.molmet.2020.02.015
EP  - 7
PY  - 2020///
SN  - 2212-8778
SP  - 1
TI  - Effects of corticosterone within the hypothalamic arcuate nucleus on food intake and body weight in male rats
T2  - Molecular Metabolism
UR  - http://dx.doi.org/10.1016/j.molmet.2020.02.015
UR  - https://www.sciencedirect.com/science/article/pii/S2212877820300454?via%3Dihub
UR  - http://hdl.handle.net/10044/1/77368
VL  - 36
ER  -
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