Dietary amino acids and their contribution to de novo lipogenesis

The alarming increase in the incidence of the metabolic syndrome is the result of the nutrition transition featuring dietary patterns high in sugars, particularly liquid carbohydrates in the form of sugary beverages, fat, and protein from red meat. The aim of this thesis was to investigate the effect of changing the solid/liquid ratio of meals on gastric emptying as well as the effect of changing meal compositions on lipid metabolism. A 5-way crossover human study demonstrated that liquid carbohydrate was the main determinant of gastric emptying rate compared to macronutrient composition and it delayed gastric emptying of the solid fraction. In this study, the energy content of the liquid portion was not sufficient to induce de novo lipogenesis, however, the high protein meal, rich in glutamate increased de novo lipogenesis-associated triacylglycerides in plasma and liver-derived very low-density lipoprotein particles in samples from human subjects. The underlying mechanism behind this increase in lipogenesis by dietary amino acids was investigated in vitro. In hepatocytes, glutamate derived carbon was incorporated into palmitate and subsequently into triacylglycerides. In addition, supplementation with glutamate, glutamine and leucine, but not lysine increased synthesised triacylglyceride content in cells and decreased glucose uptake. Glutamate, glutamine and leucine increase activation of protein kinase B, suggesting that these amino acids induce de novo lipogenesis via the insulin signalling cascade. As dietary trends have shifted towards high carbohydrate/high fat consumption, and high-protein diets are popularised as healthier alternatives, the data herein suggest that this is a more complex consideration. Therefore, advocating the consumption of protein in the treatment of diabetes and obesity requires a more profound understanding of the role.

Name dc:type.qualificationname

Doctor of Philosophy (PhD)

Level dc:type.qualificationlevel

Doctoral

Grantor dc:publisher.institution

University of Cambridge

Year dc:date.issued

2019

Author dc:creator

• Charidemou, Evelina

Advisor dc:contributor.advisor

• Griffin, Julian

• De novo lipogenesis
• Dietary amino acids
• Metabolic syndrome

Licence

• https://www.repository.cam.ac.uk/bitstreams/5383ce7d-8cee-4efc-9fd4-565652e2df94/download
• https://www.rioxx.net/licenses/all-rights-reserved/

Language dc:language

en

DOI dc:identifier.doi

https://doi.org/10.17863/CAM.40126

OAI identifier oai:identifier

oai:www.repository.cam.ac.uk:1810/292975