Metabolism in patients, with emphasis on medical nutrition and muscle wasting
Loss of muscle mass and function are commonly occurring during the progression of various chronic diseases, including HIV, COPD, cancer, diabetes and obesity. Muscle wasting or cachexia is to be considered a serious medical condition as it contributes to increased morbidity and mortality. Moreover, it can contribute to increased treatment-induced toxicities, to a reduction in treatment efficacy and to impaired quality of life.
Chronic low- and high-grade inflammatory processes are now commonly regarded major causes of muscle loss (cachexia). The figure below depicts the factors and organs involved in disease-induced muscle wasting.
The research in our group within the Division of Human Nutrition and Health aims to develop multi-targeted nutritional and pharmacological intervention strategies to achieve prevention or treatment of muscle loss.
GI-function, GI integrity and protein metabolism
The intestinal epithelium forms an effective barrier to toxins, pathogens and the bacterial gut flora. A decrease in the integrity of the gut barrier function induces inflammation, which on its turn might trigger muscle wasting. The topic of Lonneke Janssen Duijghuijsen focuses on changes in protein metabolism during inflammation-induced increases in gut permeability. In a cooperation with the VU, Joanna Luttikhold focuses on the ability to influence gut protein metabolism in humans by distribution of tube feed at different sites in the GI tract.
Cachexia and muscle wasting
The focus of this research has to a large extent been on mechanistic research in animal models for cancer cachexia, which resulted in mechanistic insight in cancer–induced cachexia and anorexia. To this purpose Rogier Plas will study the translation of the mouse data to the human situation and will perform a human mechanistic study and a retrospective study.
In cancer patients anorexia is a direct risk factor for mortality, independent of the presence of muscle loss and it further accelerates muscle loss. The research of Jvalini Dwarkasing shows that the hypothalamus in the brain appears to fail to respond adequately to changes in energy balance during cancer cachexia. Her new findings indicate that serotonin regulation might be a therapeutic target in cancer-induced eating disorders.