Ectopic fat

Project 1:

Ectopic fat

Fat accumulation in liver and muscle is one of the major determinants of metabolic health. Very little is known about the dietary factors that determine fat content in these tissues in humans, which is mainly due to the inaccessibility of liver for human studies. However, using non-invasive imaging techniques, fat accumulation and metabolism can be studied in ectopic fat stores. Especially interesting in the field of food and nutrition is the application of 13C-magnetic resonance spectroscopy (MRS) to follow ‘real-time’ the time-course of retention of dietary fat in human tissues. To this end, non-hazardous, stable isotope labelled fatty acids (13C-FAs) can be incorporated in a meal and state of the art 13C-MRS makes it possible to follow the 13C-signal real-time after a meal. The accretion and decrease of the 13C-signal in the liver and muscle will unravel the time-course of postprandial hepatic and muscular retention of FA. This unique set up will show how subjects can handle a fat load.

Therefore, the overall aim of this project is to develop and validate methodology to follow the time-course of hepatic and muscular retention of dietary fatty acids.

Key objectives:

  • To develop 13C MRS to track dietary fat retention into liver and muscle
  • To validate 13C MRS in subjects at risk for high ectopic fat accumulation
  • To implement 13C MRS in human nutritional studies

This project is financed by a grant from the Ti Food and Nutrition (TIFN)
PhD student: Lucas Lindeboom

Project 2:

Athlete’s paradox update: Lipid Deposition in Diabetic patients and Athletes

Fat accumulation in skeletal muscle is associated with the development of type 2 diabetes mellitus (T2DM). Indeed, type 2 diabetes patients have increased levels of intramyocellular lipids (IMCL). The exact mechanism of this lipid-induced insulin resistance is still under investigation. Paradoxically, endurance trained athletes show equally high IMCL stores, while they are very insulin sensitive and it is known that endurance training can increase IMCL content in muscle. The exact underlying mechanisms are yet unrevealed.

A factor that has recently gained attention is that next to the total lipid content, also specific lipid species, such as DAG and ceramides may be particularly detrimental. Reports show that insulin sensitivity was improved in overweight, insulin resistant volunteers after a 16-week endurance-training program of moderate intensity, even though IMCL was increased by 21%. Interestingly, the training resulted in a decrease in diacylglycerol and ceramide concentration.

In a mouse model was shown that the harmful diacylglycerol is associated with the membrane where they can disrupt insulin signaling instead of being stored in the form of neutral lipid droplets.

In this project, we aim to investigate the levels and localization of diacylglycerol – a fatty acid intermediate that is able to impair insulin signaling – in sedentary insulin resistant subjects and endurance trained athletes, with similar IMCL content, and compare them to a group of sedentary but insulin sensitive subjects.

This will contribute to a better understanding of the positive metabolic effects of exercise, as well as the molecular mechanisms that are responsible for the development of peripheral insulin resistance in muscle.

PhD student: Yvo op den Kamp
Collaborators: Prof. Dr. Michael Roden, Universitat Düsseldorf, Germany