Patrick Schrauwen MSc PhD

Keynote lecture: Patrick Schrauwen MSc PhD

 
"Mitochondrial Function - Involvement in type 2 diabetes and obesity"
Obesity is the major risk factor for the development of type 2 diabetes mellitus. In obesity, fat not only stores in white adipose tissue, but fatty acids can also accumulate in ectopic fat stores like heart, liver and muscle. Fat accumulation in skeletal muscle is strongly associated with the development of skeletal muscle insulin resistance, and the latter is a first hallmark in the development of type 2 diabetes mellitus. In the recent 5-6 years, a reduced mitochondrial function in skeletal muscle has been proposed to underlie the accumulation of fat in skeletal muscle. In fact, non-invasive in vivo magnetic resonance spectroscopy has revealed a reduced mitochondrial function combined with elevated muscular lipid content in type 2 diabetic patients and in pre-diabetic first-degree relatives. Ex vivo measurements have pointed towards reduced intrinsic mitochondrial function, reductions in mitochondrial density and alterations in mitochondrial structure. It is indeed tempting to suggest that these mitochondrial abnormalities could be responsible for the accumulation of fat in muscle and thereby be linked to the development of insulin resistance. Alternatively, however, mitochondrial dysfunction may be the consequence of insulin resistance and/or muscular fat accumulation. Thus, the acute elevation of circulating fatty acids reduces the expression of the transcriptional co-activator PGC1, an important transcription factor in mitochondrial biogenesis. Long-term fasting, raising circulating fatty acids, also reduced mitochondrial function. Furthermore, fatty acids that accumulate in skeletal muscle cells may exert deleterious effects to mitochondrial function (lipotoxicity) via the formation of ROS-induced lipid peroxides. Indeed, increased lipid peroxidation has been reported in insulin resistant skeletal muscle. In their defense against lipotoxicity, fatty acids have the capacity to lower mitochondrial ROS production via induction of mild uncoupling. In this presentation the current evidence for the role of mitochondrial dysfunction in the etiology of muscular insulin resistance will be evaluated. Furthermore, fatty acid induced uncoupling as a protective mechanism against lipotoxicity will be discussed.

About Patrick Schrauwen
Dr. Schrauwen received a MSc degree in movement sciences at the faculty of Health Sciences of the Maastricht University in 1994. In 1998 Dr. Schrauwen received his PhD at the Maastricht University for his thesis ‘Determinants of energy and substrate metabolism', in which human experiments on the effects of dietary fat and physical activity on body weight regulation are described. Part of his thesis was performed at the National Institutes of Health (NIH) in Phoenix (USA) where he studied molecular and genetic aspects of obesity and type 2 diabetes mellitus. In 1999 Dr. Schrauwen became a staff member at the department of Human Biology of the Maastricht University. In 1999 he was appointed a post-doc fellowship by NWO and in 2001 a prestigious Academy-fellowship from the Royal Dutch Academy of Arts and Sciences (KNAW), to examine the role of mitochondrial uncoupling proteins in skeletal muscle lipid metabolism in relation to type 2 diabetes. For his work Dr. Schrauwen was awarded the Young Investigators Award for clinical science from the European Association for the Study of Obesity in 2001, the ‘Silver Medal Award' from the Nutrition Society' in 2006 and the ‘Rising Star Award' from the European Association for the Study of Diabetes (EASD) in 2008. Dr. Schrauwen is associate editor of ‘Applied Physiology, Nutrition and Metabolism (formerly Canadian Journal of Applied Physiology). In 2008 Dr. Schrauwen received the prestigious VICI-fellowship from the Netherlands Organisation for Scientific Research (NWO/ZonMW).

His main fields of interest in research concern muscular insulin resistance, lipotoxicity and mitochondrial dysfunction with special emphasis on type 2 diabetes mellitus. The research team supervised by Dr. Schrauwen investigates whole-body, tissue and cellular physiology. To this end, molecular, genetic and whole-body techniques are used in both rodent and human models. In collaboration with the department of Radiology of the Maastricht University Hospital, Dr. Schrauwen applies non-invasive magnetic resonance spectroscopy to investigate in vivo mitochondrial function and lipid accumulation in muscle, liver and heart.