University of Surrey

Test tubes in the lab Research in the ATI Dance Research

The role of diet and gut microbiota in lipid metabolism: implications for health outcomes using a mouse model.

Ampong, Isaac (2020) The role of diet and gut microbiota in lipid metabolism: implications for health outcomes using a mouse model. Doctoral thesis, University of Surrey.

[img]
Preview
Text
PhD thesis(Isaac_Ampong).pdf - Version of Record
Available under License Creative Commons Attribution Non-commercial Share Alike.

Download (4MB) | Preview

Abstract

The prevalence of non-Alcoholic Fatty Liver Disease (NAFLD) has now reached epidemic proportions, but the role of gene-lifestyle interactions in its pathogenesis remains poorly understood. While evidence for an inverse association between odd-chain length fatty acids (OCFA) and cardiometabolic diseases, suggests a possible link between OCFAs and NAFLD, little is known about the impact of diet, gut microbiota and peroxisomal biogenesis on the metabolism of OCFAs. We hypothesized that suboptimal diet, altered gut microbiota and peroxisomal biogenesis could promote the development of NAFLD by impairing the metabolism of OCFAs. This thesis aimed to understand the effect of dietary fat/protein on the genetic and metabolic regulation of lipids and OCFAs in relation to NAFLD, using a high fat diet (HFD) model, well established in the literature for inducing obesity and insulin resistance in mice within 4 weeks, and a low protein diet (LPD) model, known to promote NAFLD. Under specific pathogen free or normal husbandry conditions, a HFD reduced serum OCFA in mice after 4 and 12 weeks of feeding, and down-regulated the activity of several key enzymes in fatty acid metabolism (desaturases, lyase, elongase). Liver histology also showed deposition of lipid droplets and higher expression of peroxin 14 protein in HFD fed mice (Chapter 3). The characterisation of gut microbiota revealed an alteration in propionate-producing bacteria, Lachnospiraceae and Clostridiales, in HFD fed mice (Chapter 4). Mice fed with carbohydrate rich-LPD for 7 weeks resulted in lower levels of serum OCFA, increased CD36 mRNA and peroxin 14 expressions. However, OCFA did not change in the reduced and quality carbohydrate-LPD after 8 weeks (Chapter 5). In conclusion, these findings provide evidence that HFD and carbohydrate rich-LPD reduced OCFA via changes in gut microbiota and peroxisomal biogenesis in the liver and increases our understanding of how suboptimal diets contributes to NAFLD.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors : Ampong, Isaac
Date : 30 June 2020
Funders : Commonwealth Scholarship Commission in the UK
DOI : 10.15126/thesis.00857061
Contributors :
ContributionNameEmailORCID
http://www.loc.gov/loc.terms/relators/THSGriffiths, Helenh.r.griffiths@surrey.ac.uk
Gutierrez, Jorgej.gutierrez@surrey.ac.uk
Depositing User : Isaac Ampong
Date Deposited : 09 Jul 2020 15:19
Last Modified : 09 Jul 2020 15:19
URI: http://epubs.surrey.ac.uk/id/eprint/857061

Actions (login required)

View Item View Item

Downloads

Downloads per month over past year


Information about this web site

© The University of Surrey, Guildford, Surrey, GU2 7XH, United Kingdom.
+44 (0)1483 300800