The nutritional geometry of non-alcoholic fatty liver disease, cardio-metabolic health and lifespan

Summary

The global epidemic of obesity and type 2 diabetes (T2D) has been linked to increased consumption of ‘western diets’ containing an abundance of processed foods rich in saturated fats and ‘simple carbohydrates’. Furthermore, increased intake of sugars and fats promotes the development of non-alcoholic fatty liver disease (NAFLD) - the commonest form of liver disease in the Western world, affecting one in three people in the general population. Accumulation of liver fat is thought to be a principal driver of T2D, and it is usually associated with dyslipidaemia, particularly increased circulating triglycerides. The fat deposition in NAFLD can be caused by an increase in endogenously synthesised fatty acids in the liver (de novo lipogenesis), by increased consumption of dietary fatty acids that are subsequently stored in the liver, or both. Using the Geometric Framework research methodology, we will investigate how different dietary nutrients affect liver biology, late-life cardiometabolic health status and longevity.  

A complimentary scholarship for this project may be available through a competitive process. To find out more, refer to the Faculty of Science Postgraduate Research Excellence Award and contact Dr Jibran Wali directly.

Supervisor(s)

Professor Stephen Simpson, Dr Jibran Wali

Research Location

School of Life and Environmental Sciences

Program Type

PHD

Synopsis

The Geometric Framework (GF) - a nutritional modelling platform - has revolutionized our capacity to interpret the complex relationship between food and phenotype. In the GF, a model of an animal’s nutritional relations with its environment is constructed around an n-dimensional nutrient space (e.g. protein, carb and fat) and phenotypic parameters (e.g. fat mass) are superimposed on this space by plotting response surfaces. This allows analysis of macronutrient intake targets of animals, their feeding response to diets with different compositions, and its impact on performance characteristics. Our research using the GF has robustly shown in invertebrates and mice that diets low in protein and high in carbohydrate content generate the best metabolic health and lifespan outcomes despite increased energy intake (‘protein leverage’). In this advertised project we will extend our work by investigating how the source of dietary protein (animals vs plant), fat (animal vs plant) and type of carbohydrate (simple vs complex) regulates cardiometabolic health, liver fat deposition and lifespan using the laboratory mice as a model organism. We will study how different types of carbohydrates (glucose, fructose, starch and sucrose) interact with protein and fat to drive the pathogenesis of fatty liver, obesity and insulin resistance. The study will be conducted at the Charles Perkins Centre and will include male and female mice maintained on diets with different ratios of protein, fat and carbohydrates derived from various sources. The PhD candidate will be involved in animal husbandry, in vivo metabolic phenotyping, animal dissections and in vitro assessment of tissue health by molecular biology techniques (qPCR, ELISA, western blotting and histology).

Additional Information

A complimentary scholarship for this project may be available through a competitive process. To find out more, refer to the Faculty of Science Postgraduate Research Excellence Award and contact Dr Jibran Wali directly. 

Applicants should have an interest and background in biochemistry, molecular biology and metabolism. Previous laboratory experience in metabolic biochemistry and mouse research is strongly recommended.

HDR Inherent Requirements  

In addition to the academic requirements set out in the Science Postgraduate Handbook, you may be required to satisfy a number of inherent requirements to complete this degree. Example of inherent requirement may include:    

  • Confidential disclosure and registration of a disability that may hinder your performance in your degree;
  • Confidential disclosure of a pre-existing or current medical condition that may hinder your performance in your degree (e.g. heart disease, pace-maker, significant immune suppression, diabetes, vertigo, etc.);
  • Ability to perform independently and/or with minimal supervision;  
  • Ability to undertake certain physical tasks (e.g. heavy lifting);  
  • Ability to undertake observatory, sensory and communication tasks;  
  • Ability to spend time at remote sites (e.g. One Tree Island, Narrabri and Camden);  
  • Ability to work in confined spaces or at heights;  
  • Ability to operate heavy machinery (e.g. farming equipment);  
  • Hold or acquire an Australian driver’s licence;  
  • Hold a current scuba diving license;  
  • Hold a current Working with Children Check;  
  • Meet initial and ongoing immunisation requirements (e.g. Q-Fever, Vaccinia virus, Hepatitis, etc.)   

You must consult with your nominated supervisor regarding any identified inherent requirements before completing your application.

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Keywords

nutrition, Liver, metabolism, lifespan

Opportunity ID

The opportunity ID for this research opportunity is: 2724