Understanding diet-induced metabolic dysfunction

8 June 2016 – Eating large amounts of animal fat and a high-cholesterol diet contribute to metabolic dysfunction in liver and fat tissue. Inflammation of fat tissue is the most damaging contributor to the development of type 2 diabetes – an insight that could be used to develop and improve targeted therapies. This is the key outcome of the work of TiFN’s PhD fellow Dr Roel van der Heijden. He defended his thesis May 23, 2016 at the University of Groningen. 

Obesity is a worldwide issue, causing c. 2.8 million deaths per year. Dietary intervention doesn’t work, so it is important to understand, at the metabolic level, how obesity and obesity-related diseases, develop over time.

Investigating these processes in humans is difficult, due to their slow progression and people appearing to be symptom-free for many years. Van der Heijden worked with mice, for their short lifespan. “I investigated how high concentrations of animal fat and cholesterol contribute to a disturbed metabolism in fat and liver tissue respectively how these disturbances contribute to increased concentrations of inflammation markers and lipids in the blood”, he explains. “I also explored how these blood values contribute to future damage to the vascular system.”

Van der Heijden saw that only 24 weeks on a diet high in animal fat already increased blood levels of inflammatory markers. Enriching the high-fat diet with anti-inflammatory polyphenols (epicatechin and anthocyanins) did not have a lasting positive impact on inflammatory markers. “In the case of a high-cholesterol diet, however, enrichment with polyphenols was able to attenuate some of these markers and halt the progression of vascular disease”, he stresses. “This underlines the importance of identifying the dietary triggers for metabolic dysfunction, and the organ assessed.”

Interdisciplinary approach
The PhD recommends an interdisciplinary approach to the prevention and treatment of obesity and obesity-related diseases. “In addition to diet, aspects like genetic disposition, ageing and the composition of the microbiota, probably have roles in metabolic dysfunction.”