Award details

Regulation of Metabolic Homeostasis

Reference	BBS/E/F/000PR10347
Principal Investigator / Supervisor	Dr Paul Kroon
Co-Investigators / Co-Supervisors	Dr Naiara Beraza, Professor Leanne Hodson
Institution	Quadram Institute Bioscience
Department	Quadram Institute Bioscience Department
Funding type	Research
Value (£)	2,967,199
Status	Current
Type	Institute Project
Start date	01/04/2018
End date	31/03/2023
Duration	47 months

Abstract

The overall aim of Theme 4 is to provide a mechanistic understanding for the manner by which non-nutrient food and microbiota-derived food metabolites regulate the metabolism of lipids and carbohydrates and modulate overall energy expenditure to maintain and improve health. We will do that by focusing on the two major metabolic organs: the liver, where the transient influx of high concentrations of these metabolites will be exerting ‘first-pass’ effects on lipid and glucose metabolism following their absorption from the gastrointestinal tract, and the organ-associated and peripheral adipocytes, where bioactive compounds can impact on energy sensing and expenditure. We will use human cell lines but also appropriate animal models to elucidate the role of nrf2 and sirt1 as the mediators of energy metabolism by food and their metabolites. In particular, we will use novel genome editing techniques by CRISPR/Cas9 in human hepatocytes, as well as sirt1 knockdown and overexpressed mouse models, developed in QIB. In addition, we will undertake human intervention studies with stably labelled fatty acids to enable quantification of hepatic and whole body fatty acid oxidation and lipid synthesis, in response to different diets developed in Theme 1. By combining the results obtained at the cellular and organ levels, we will gain a clear understanding of how diets regulate systemic metabolic homeostasis.

Summary

unavailable

Committee	Not funded via Committee
Research Topics	X – not assigned to a current Research Topic
Research Priority	X – Research Priority information not available
Research Initiative	X - not in an Initiative
Funding Scheme	X – not Funded via a specific Funding Scheme

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