Metabolic Regulation group

Our main goal in the field of metabolic regulation is to elucidate the enzymatic, structural and metabolic basis for the homeostatic mechanisms and dynamics of the living (animal and human) organism.

We study the processes under normal as well as pathological conditions and the research area can be understood as a bridge between molecular biology and physiology as well as clinical science.

The research area is also of central importance for the understanding of nutritional questions. There is a clearly increasing demand for knowledge in the field of metabolism, as best illustrated by the mitochondrial involvement in type 2 diabetes.

Research activities 

Our research interests are within the area of 'Metabolic programming' and 'Regulation of energy metabolism'. Read more about our research activities on this page. 

Metabolic programming

Fetal programmingMaternal nutrition during gestation may determine the metabolic phenotype of the offspring. This concept is supported by the fact that low birth weight (LBW), a hallmark of inappropriate gestational nutrition, has been shown to be an independent risk factor for obesity, insulin resistance and type 2 diabetes in adult life of the LBW individual. Interestingly, recent research suggests the same end-point vulnerability of of an individual also as a result of overfeeding during gestation. 

The mechanism behind such gestational programming of the metabolic phenotype is unknown, but epigenetic modifications are implicated, either by DNA methylation or by histone modifications. Since mitochondrial dysfunction has been observed in relation with the development of obesity and insulin resistance, we are looking for changes in the expression of genes related to various aspects of mitochondrial function. Thus, our studies are aimed at combining detection of functional mitochondrial changes with expression changes of relevant regulatory genes and the corresponding changes at the protein levels as well as the physiological phenotype and intracellular signalling.

The observations have been made in vitro with cell culture systems or isolated mitochondria from muscle, liver and fat tissue from mouse, rat and sheep. Also, genetically diabetic rat strains (GK and ZDF) are used as experimental models. As an example, we have established that a low protein diet during gestation results in >1000 specific gene expression changes, the majority of which are related to mitochondrial metabolism. These changes appear to be tissue specific, and are, surprisingly, subject to a significant rescue effect by taurine supplementation (in the drinking water) during pregnancy. Currently, we are following these studies up with non-invasive NMR spectroscopy on human skeletal muscle, estimating the actual capacity for ATP synthesis in vivo. The results suggest, that mitochondrial functions other than the in vivo capacity for ATP turnover, which are affected by the metabolic programming.

Mitochondrial production of reactive oxygen species (ROS) is a possibility link between nutrition and insulin resistance, since they may induce inflammatory processes. Mechanisms for such a link are elucidated by studies of long term effects of dietary components such as fructose which may activate inflammatory pathways, or taurine which may affect the general thiol redox state of the tissues. Intracellular mechanisms are being pursued by studies of intracellular signalling combined with functional studies of mitochondria.

Regulation of energy metabolism

Another line of research is on regulation of energy metabolism in human brain and skeletal muscle. In skeletal muscle we have established an explanation of the long standing ‘riddle' as to why glycolysis in muscle is intimately coupled to contraction and shown it to be a consequence of the fundamental structure of the metabolic network of ATP turn over. In the human brain we have established that lactate fuels cerebral energy metabolism as efficiently as glucose and that the lactate/pyruvate redox ratio of the blood plasma may be part of the mechanism governing the cerebral blood flow, thereby potentially forming a metabolic redox coupling between brain and other major organs of the body.