Research

Research

Reseach

Research of the group of prof. Patrick C.N Rensen focuses on better understanding the role of various organs in glucose and lipid metabolism and their consequences for obesity, type 2 diabetes, NASH and cardiovascular disease. The ultimate aim is to discover novel therapeutic handles to prevent and combat these diseases. Various research lines within the group are:

Brown adipose tissue

While the main function of white adipose tissue (WAT) is to store energy in the form of lipids (known as triglycerides), brown adipose tissue (BAT) combusts these lipids into heat, a process referred to as ‘adaptive thermogenesis’. Brown fat depots are strategically localized in the scapular area near the large arteries, where heat production appears to be essential for the survival of small mammals in cold environments and for arousal of hibernators.

Since activated BAT has a high capacity to take up and burn lipids and glucose, BAT is considered a promising target to combat adiposity and associated diseases, including diabetes and cardiovascular disease.

Circadian rhythmicity

Modern society predisposes to the disruption of the physiological circadian rhythms as we are increasingly confronted with a 24-hour economy, resulting in exposure to light, activity and feeding at night. Disturbances in circadian rhythmicity by for example shift-work are associated with increased risk for the development of obesity and cardiovascular diseases. However, the underlying mechanisms are still unclear. 

Non-alcoholic steatohepatitis

Non-alcoholic steato-hepatitis (NASH) is a fatty inflamed liver not associated with alcohol abuse; it is a key feature of the metabolic syndrome. NASH is thought to start with ectopic lipid accumulation in the liver that is caused by obesity-associated changes in fatty acid partitioning. The chronic presence of excess lipids in the liver subsequently causes a pro-inflammatory state that result in the progression from a fatty liver to a fatty and inflamed liver. However, the complete sequence of events and the molecular mechanisms underlying the association between fatty acids and inflammation, and the subsequent development of hepatic pathology are unknown.

Gut microbiome

There are over 100 trillion microbes that reside in our bodies. The gut microbiome is regarded as a hidden organ that has emerged as a critical regulator of host biology. Gut microbiota ferment fibers and produce short-chain fatty acids that modulate energy metabolism. The gut microbiome varies between individuals and can fluctuate due to various genetic and lifestyle factors, but also due to antibiotic utilization. The plasticity of the gut microbiome composition suggests that manipulating the gut microbiome may be useful as a personalized therapeutic strategy in metabolic disorders. However, the causal relationships between gut microbes and host energy metabolism and the underlying mechanisms remain mostly unresolved.

Heart-on-chip

Organ-on-chip models are used to mimic the complex functions of organs in vitro by culturing cells inside microfluidic chambers. Using heart-on-chip technology human induced pluripotent stem cell (hiPSC)-derived cardiomyocytes can be cultured in a beating 3D configuration with the ultimate goal to mimic the human heart. However, currently hiPSC-derived cardiomyocytes are metabolically immature and mainly use glucose as an energy source instead of fatty acids that are primarily used by the human heart. We aim to develop a highly human-predictive heart-on-chip model by switching the metabolism of the cells to fatty acid oxidation. Metabolic cell maturation would make heart-on-chip systems suitable for the screening of drugs that target metabolic pathways, such as LPL activating drugs for reducing cardiovascular disease risk.

Exercise

Physical activity in the form of exercise is a valuable tool in the prevention and treatment of cardiometabolic diseases such as obesity, diabetes and atherosclerosis. It is increasingly prescribed by physicians to delay or avoid pharmacological interventions or in a combination therapy. Skeletal muscle is the largest metabolic organ in the body and can modulate whole-body lipid and glucose metabolism. Active muscles communicate with other tissues like the liver, fat tissues and the brain but the underlying molecular mechanisms of how skeletal muscle acts as an endocrine organ are not entirely understood yet.
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