Understanding the impact of a cholesterol-rich diet role on hepatic liver metabolism using mathematical models: focus on gender differences

Vanessa Diaz (primary)
Mechanical Engineering
University College London
Ines Pineda-Torra (secondary)
Division of Medicine, Centre for Clinical Pharmacology
University College London

Abstract

We will use mathematical models to test hypotheses to understand a key biological question: the impact of a cholesterol-rich diet on the regulation of hepatic liver metabolism. Cholesterol-rich diets affect hepatic metabolic pathways and their regulation is controlled by several transcription factors including the master lipid regulator LXR. We aim to better understand how nutritional modulation of LXR affects hepatic lipid metabolism and whether differences between genders exist. We have animals carrying a mutation in LXR which disrupts liver metabolic pathways. We will use existing multi-parameter datasets from these mice to establish signatures and models to predict metabolic outcomes by gender.


References

Liver X receptors in lipid metabolism: opportunities for drug discovery. Hong C, Tontonoz P. Nat Rev Drug Discov. 2014 Jun;13(6):433-44.

Pichardo–Almarza, C et al. CPT: Pharmacometrics & Systems Pharmacology 4, 1-10 (2015).

Torra, I. P. et al. Phosphorylation of liver X receptor alpha selectively regulates target gene expression in macrophages. Mol. Cell. Biol. 28, 2626–2636 (2008).


BBSRC Area
Genes, development and STEM* approaches to biology
Area of Biology
Cell BiologyPhysiology
Techniques & Approaches
BiochemistryBiophysicsEngineeringMolecular BiologySimulation / Modelling