To increase clinical success rate of drugs, a better understanding of drug action mechanism and disease dynamics is required. Metabolomics, which studies small molecules involved in biochemical... Show moreTo increase clinical success rate of drugs, a better understanding of drug action mechanism and disease dynamics is required. Metabolomics, which studies small molecules involved in biochemical processes in organisms, has shown to be a useful tool for this better understanding. In this thesis, we focus on the endocannabinoid system (ECS) and profiling its related metabolic pathways using liquid chromatography - mass spectrometry (LC-MS) based metabolomics techniques. The endocannabinoid system (ECS) is a signaling system involved in multiple physiological and pathological processes. Due to its wide distribution and complex network of metabolic interactions, the development of drugs targeting the ECS has seen high failure rates. To get a better understanding of the behavior of the ECS and related pathways, LC-MS platforms with wide coverage of the major ECS-related metabolites, or with high sensitivity that reaches low levels of metabolites, were developed and optimized. Furthermore, these metabolomics platforms were applied in clinical studies looking into cardiometabolic health, and revealed correlations between endogenous metabolite signaling, cardiometabolic health and the benefits of exercise. Show less
Disruption of circadian (similar to 24 h) rhythms is associated with an increased risk of cardiometabolic diseases. Therefore, unravelling how circadian rhythms are regulated in different metabolic... Show moreDisruption of circadian (similar to 24 h) rhythms is associated with an increased risk of cardiometabolic diseases. Therefore, unravelling how circadian rhythms are regulated in different metabolic tissues has become a prominent research focus. Of particular interest is brown adipose tissue (BAT), which combusts triglyceride-derived fatty acids and glucose into heat and displays a circannual and diurnal rhythm in its thermogenic activity. In this review, the genetic, neuronal and endocrine generation of these rhythms in BAT is discussed. In addition, the potential risks of disruption or attenuation of these rhythms in BAT, and possible factors influencing these rhythms, are addressed. Show less
