Phenotyping the effects of nutrient quality on metabolic health: starring the liver & adipose tissue

Research output: Thesisinternal PhD, WU


The growing burden of obesity-related pathologies calls for effective dietary strategies that improve metabolic health of overweight and obese individuals. An evidently effective dietary strategy to correct metabolic parameters associated with chronic diseases is limiting the intake of daily calories, i.e. energy restriction (ER). In addition to lowering the energy quantity of the diet, increasing the quality of the diet by consuming more high quality nutrients can also be an appealing dietary approach. However, measuring the effects of dietary strategies is challenging as effects of nutrition on health are usually relatively subtle may take a long time to manifest. In addition, classical blood markers assessed in nutritional intervention studies are typically late disease markers. To be able to more precisely assess the effect of dietary interventions and to elucidate underlying mechanisms, we need to adopt a comprehensive phenotyping approach in which we combine classical markers with sensitive measures, such as the ability of an individual to deal with a dietary stressor, i.e. phenotypic flexibility, and extensive high-throughput techniques. The aim of this thesis was to assess the effects of nutrient quality on metabolic health with a specific focus on the liver and adipose tissue, in overweight and obese individuals.

We examined the effects of nutrient quality within eucaloric diets by comparing the differential effects of refined wheat and whole grain wheat products in overweight and obese individuals. Consumption of the low nutrient quality refined wheat resulted in a pronounced increase in intrahepatic lipids along with a decrease in gut microbiota diversity. Whole grain wheat consumption induced a trend towards lower liver inflammatory markers. Incorporating feasible doses of whole grain wheat in the diet at the expense of refined wheat thus favorably affects liver health. We examined the effects of nutrient quality within ER diet by comparing the differential effects of a high quality ER-diet rich in soy protein, fiber, MUFA, and n-3 PUFA, a low nutrient quality Western-type ER-diet and a control group in subjects with abdominal obesity. Both diets induced clinically relevant weight loss, accompanied by reductions in abdominal fat mass and intrahepatic lipids. Despite equal ER, participants in the high quality diet group lost a third more when compared to Western-type diet group, which resulted in larger adaptations in adipose tissue energy metabolism. Both ER-diets alleviated metabolic complications associated with abdominal obesity, such as reductions in blood pressure and improvements in systemic markers related to glucose homeostasis and insulin sensitivity. Only the high quality diet beneficially affected fasted blood lipid profile by reducing plasma triglycerides and total serum cholesterol, which was mainly caused by a reduction in medium and large very low density lipoprotein (VLDL) particles. Both ER-diets reduced postprandial responses of VLDL, intermediate density lipoproteins (IDL), and low density lipoproteins (LDL) after a mixed meal but these effects were more pronounced in the high quality diet.  

To conclude, consumption of whole grain wheat might prevent intrahepatic lipid accumulation and thus lower non-alcoholic fatty liver disease risk, while a weight loss diet rich in soy protein, fiber, MUFA, and n-3 PUFA holds great potential in lowering the risk of cardiovascular diseases, such as atherosclerosis. This thesis shows that it does matter which nutrients are emphasized within diets. The findings have increased our understanding of the effects of nutrient quality on metabolic health, mediated by the liver and adipose tissue, and can aid in designing optimal dietary strategies to combat pathologies associated with obesity.

Original languageEnglish
QualificationDoctor of Philosophy
Awarding Institution
  • Wageningen University
  • Kersten, Sander, Promotor
  • Afman, Lydia, Co-promotor
Award date31 Aug 2018
Place of PublicationWageningen
Print ISBNs9789463437776
Publication statusPublished - 2018


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