Our increasing obesogenic and aging society has resulted in a steeply increasing prevalence of cardiometabolic diseases. The main underlying reason is our modern lifestyle with respect to higher... Show moreOur increasing obesogenic and aging society has resulted in a steeply increasing prevalence of cardiometabolic diseases. The main underlying reason is our modern lifestyle with respect to higher availability and intake of food, which often appears unhealthy, and lower energy expenditure related to a sedentary lifestyle. Although the most efficient ways to slow this high prevalence of obesity are just eating less and more healthy, and moving more, to reduce energy intake and increase energy expenditure, respectively, current strategies to achieve this in the long-term are still both insufficient and ineffective, and novel strategies are still eagerly warranted.This thesis emphasizes dietary butyrate as a promising and feasible therapeutic strategy to combat obesity and related cardiometabolic diseases with respect to not only reducing appetite but also activating brown adipose tissue. In a series of subsequent mechanistic studies, we elucidated the mechanisms underlying these metabolic properties systematically from gut to the brain, showing the involvement of gut microbiota, intestinal GLP-1 secretion, vagal nerve activation, and finally central GLP-1 receptor signaling to inhibit NPY neuronal activation. The findings of this thesis provide valuable information on the development of novel therapeutic strategies for combating obesity and associated cardiometabolic diseases. Show less
Atherosclerosis is the underlying cause of most cardiovascular diseases. The evidence to support a cholesterol-atherosclerosis link has been revealed in the past three decades. There is a growing... Show moreAtherosclerosis is the underlying cause of most cardiovascular diseases. The evidence to support a cholesterol-atherosclerosis link has been revealed in the past three decades. There is a growing consensus that therapeutic lowering of plasma VLDL- and LDL-cholesterol levels and raising of HDL-cholesterol level will reduce the risk of cardiovascular incidence. This dissertation is dedicated to the regulation of lipid metabolism pathways, both in plasma and liver, and its subsequent effects on atherosclerotic lesion progression and regression. The first part of the thesis focuses on the hepatic lipid metabolism and the pharmaceutical interventions in the liver. The second part of the thesis focuses on the concept of atherosclerotic lesion regression, shedding insights in the role of LXR activation and application of mouse models in regression studies. In Chapter 8, the results obtained from all the experiments mentioned above are summarized and discussed with respect to the implications of these studies for future investigations. Show less
