Imperial College London
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ProfessorJulianGriffin

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Visiting Professor
 
 
 
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Contact

 

+44 (0)20 7594 3220julian.griffin

 
 
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Location

 

Sir Alexander Fleming BuildingSouth Kensington Campus

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Summary

 

Publications

Citation

BibTex format

@article{Charidemou:2019:10.1172/jci.insight.124819,
author = {Charidemou, E and Ashmore, T and Li, X and McNally, BD and West, JA and Liggi, S and Harvey, M and Orford, E and Griffin, JL},
doi = {10.1172/jci.insight.124819},
journal = {JCI insight},
pages = {1--21},
title = {A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans},
url = {http://dx.doi.org/10.1172/jci.insight.124819},
volume = {4},
year = {2019}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - BACKGROUND. Dietary changes have led to the growing prevalence of type 2 diabetes andnonalcoholic fatty liver disease. A hallmark of both disorders is hepatic lipid accumulation, derivedin part from increased de novo lipogenesis. Despite the popularity of high-protein diets for weightloss, the effect of dietary protein on de novo lipogenesis is poorly studied. We aimed to characterizethe effect of dietary protein on de novo lipid synthesis.METHODS. We use a 3-way crossover interventional study in healthy males to determine theeffect of high-protein feeding on de novo lipogenesis, combined with in vitro models to determinethe lipogenic effects of specific amino acids. The primary outcome was a change in de novolipogenesis–associated triglycerides in response to protein feeding.RESULTS. We demonstrate that high-protein feeding, rich in glutamate, increases de novolipogenesis–associated triglycerides in plasma (1.5-fold compared with control; P < 0.0001) andliver-derived very low-density lipoprotein particles (1.8-fold; P < 0.0001) in samples from humansubjects (n = 9 per group). In hepatocytes, we show that glutamate-derived carbon is incorporatedinto triglycerides via palmitate. In addition, supplementation with glutamate, glutamine, andleucine, but not lysine, increased triglyceride synthesis and decreased glucose uptake. Glutamate,glutamine, and leucine increased activation of protein kinase B, suggesting that induction of denovo lipogenesis occurs via the insulin signaling cascade.CONCLUSION. These findings provide mechanistic insight into how select amino acids induce denovo lipogenesis and insulin resistance, suggesting that high-protein feeding to tackle diabetes andobesity requires greater consideration.FUNDING. The research was supported by UK Medical Research Council grants MR/P011705/1, MC_UP_A090_1006 and MR/P01836X/1. JLG is supported by the Imperial Biomedical Research Centre,National Institute for Health Research (NIHR).
AU  - Charidemou,E
AU  - Ashmore,T
AU  - Li,X
AU  - McNally,BD
AU  - West,JA
AU  - Liggi,S
AU  - Harvey,M
AU  - Orford,E
AU  - Griffin,JL
DO  - 10.1172/jci.insight.124819
EP  - 21
PY  - 2019///
SN  - 2379-3708
SP  - 1
TI  - A randomized 3-way crossover study indicates that high-protein feeding induces de novo lipogenesis in healthy humans
T2  - JCI insight
UR  - http://dx.doi.org/10.1172/jci.insight.124819
UR  - http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000472162400003&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=1ba7043ffcc86c417c072aa74d649202
UR  - https://insight.jci.org/articles/view/124819
UR  - http://hdl.handle.net/10044/1/72157
VL  - 4
ER  -
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