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
In this thesis we focused on the causes and consequences of hepatic steatosis. Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between... Show moreIn this thesis we focused on the causes and consequences of hepatic steatosis. Epidemiological studies in humans, as well as experimental studies in animal models, have shown an association between visceral obesity and dyslipidemia, insulin resistance and type 2 diabetes mellitus. The mechanism underlying this association remains unclear. Recently, attention has focused on the role of excessive accumulation of triglycerides (TG) in the liver (hepatic steatosis) in this association. Hepatic steatosis was considered a benign condition until it was discovered that a nonalcoholic fatty liver is associated with many cardiovascular risk factors. Subsequently, many studies have shown a strong association between hepatic TG content and hepatic insulin resistance. The studies in this thesis show that hepatic steatosis is actively and passively involved in the metabolic disturbances in the glucose and lipid metabolism. The prevalence of hepatic steatosis in western countries is high and will certainly increase with the epidemics of obesity and diabetes. This will put an increasing number of subjects at risk for disturbances in the glucose and lipid metabolism and concomitantly for cardiovascular disease. Show less
