The brain is increasingly recognized as the regulator of body homeostasis and as possible treatment target for cardiovascular disease. This thesis further reveals the role of the autonomic nervous... Show moreThe brain is increasingly recognized as the regulator of body homeostasis and as possible treatment target for cardiovascular disease. This thesis further reveals the role of the autonomic nervous system (ANS) in the control of lipid metabolism and inflammation, and identified pathological consequences of disturbed regulation. Part I focuses on regulation of lipid metabolism by the ANS, with special attention for brown adipose tissue (BAT) as an emerging pharmacological target for therapy. We describe novel targets that modulate BAT, both directly (e.g. CB1R) and via the brain (e.g. MC4R, GLP-1R) to show that BAT activation improves dyslipidemia, glucose tolerance and T2D and even atherosclerosis. In addition, we identified the biological clock as an important regulator of BAT function and showed the consequences of disturbed circadian rhythmicity for lipid metabolism. Part II of this thesis describes studies on the regulation of inflammation by the ANS, with focus on the anti-inflammatory reflex. During this reflex, binding of acetylcholine to _7nAChR and subsequent intracellular signaling results in transcriptional repression of pro-inflammatory genes. We investigated the effects of hematopoietic _7nAChR deficiency and the consequences of selective parasympathetic and sympathetic denervation of the spleen for this reflex, and for inflammation and atherosclerotic plaque development. Show less
