Obesity has a great societal impact as it contributes to the development of type 2 diabetes and cardiovascular diseases. Activation of brown adipose tissue (BAT) is seen as a strategy to combat... Show moreObesity has a great societal impact as it contributes to the development of type 2 diabetes and cardiovascular diseases. Activation of brown adipose tissue (BAT) is seen as a strategy to combat adiposity and related disorders, because of its capacity to combust nutrients and increase energy expenditure. To develop novel BAT activating methods, a better understanding of the pathophysiology of diet-induced obesity on BAT function and whole-body metabolism is required. Studies described in this thesis have increased our understanding of nutrient handling by brown adipocytes. We also generated immortalized brown adipocytes which can be used for future research. Furthermore, we gained more insight into the development of diet-induced obesity; feeding a high fat diet (HFD) rapidly made BAT insulin resistant and less active. In addition, HFD feeding increased synthesis of so-called endocannabinoids in both white and brown adipose tissue. Because endocannabinoids regulate both energy intake and expenditure, future research should determine whether inhibiting endocannabinoid signaling specifically in adipose tissue is a worthwhile strategy to pursue in combating obesity. Finally, quercetin, which naturally occurs in fruits and vegetables, induced ‘browning’ of white adipose tissue and thereby improved blood lipid levels. These studies pave the road for further development of BAT-activating strategies! Show less
People of South Asian origin have an increased risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD) compared to people of Western European descent. Not only is the prevalence... Show morePeople of South Asian origin have an increased risk of developing type 2 diabetes (T2D) and cardiovascular disease (CVD) compared to people of Western European descent. Not only is the prevalence of these diseases higher in South Asians, they also occur at a younger age and lower BMI, and have a more severe course. The high prevalence of T2D and CVD in South Asians, who comprise one fifth of the total world__s population, poses a major health and socioeconomic burden worldwide. The underlying cause of this excess risk is, however, still poorly understood. The studies described in this thesis were performed to gain more insight in the pathogenesis of T2D and CVD in South Asians and to provide new leads for preventive strategies and treatment options. For this purpose sophisticated techniques were used such as hyperinsulinemic-euglycemic clamp with stable isotopes, indirect calorimetry, skeletal muscle biopsies, MRI and spectroscopy, and brown fat quantification using PET-CT-imaging, combined with short-term dietary interventions, in healthy lean young adult men and overweight adult men. These studies have led to a number of promising areas for further research. It seems that not one, but multiple metabolic mechanisms have been affected, most likely due to gene-environment interactions. Show less
