- Author
-
N.M. Held
- Title
- Exploring cellular metabolism to improve cardiometabolic health
- Supervisors
-
R.H.L. Houtkooper
- Co-supervisors
-
M. van Weeghel
F.M. Vaz - Award date
- 4 February 2020
- Number of pages
- 256
- ISBN
- 9789463756990
- Document type
- PhD thesis
- Faculty
- Faculty of Medicine (AMC-UvA)
- Abstract
-
Cardiometabolic disease starts with insulin resistance and can progress to metabolic syndrome, pre-diabetes, type 2 diabetes and eventually to cardiovascular disease. All of these are not only a health burden, but also an economic burden, and unfortunately expected to increase. Research strategies to combat obesity- related disease have focused on lifestyle alterations such as diet and exercise, and molecular targets that can restore energy homeostasis. We have come to learn that some people have reduced resting metabolic rates that make them burn less energy on a daily basis. This is one of the factors explaining why some people gain weight while others do not, even when they have the same diet. Reduction of expenditure is now recognized as a risk factor for weight gain. Therefore, improving energy metabolism is a promising means of targeting obesity. Mitochondria play a central role in energy metabolism and numerous studies indicate that mitochondrial dysfunction contributes to the pathogenesis of cardiometabolic disease. Over the last 20 years, researchers have attempted to develop means of improving mitochondrial function to treat cardiovascular disease. This thesis aims to describe the role of mitochondrial function in the maintenance of cardiometabolic health. The aim of this thesis has been divided into three parts, describing three objectives. First, to gain more insight into the molecular mitochondrial mechanisms that contribute to cardiometabolic health. Second, to show how mitochondrial dysfunction affects cardiometabolic health. And third, to investigate metabolic pathways that could contribute to cardiometabolic health.
- Persistent Identifier
- https://hdl.handle.net/11245.1/e4b54c00-d166-4217-87e4-bd8b21493fe2
- Downloads
-
Thesis
Front matter
Chapter 1: General introduction and thesis outline
Chapter 2: Mitochondrial quality control pathways as determinants of metabolic health
Chapter 3: Tetracycline antibiotics impair mitochondrial function and its experimental use confounds research
Chapter 4: The antibiotic doxycycline impairs cardiac mitochondrial and contractile function
Chapter 5: Barth syndrome cells display widespread remodeling of mitochondrial complexes without affecting metabolic flux distribution
Chapter 6: A single day of high fat diet feeding induces lipid accumulation and insulin resistance in brown adipose tissue in mice
Chapter 7: Pyruvate dehydrogenase complex plays a central role in brown adipocyte energy expenditure and fuel utilization during short-term beta-adrenergic activation
Chapter 8: Aging selectively dampens circadian oscillation of lipid abundance in white and brown adipose tissue
Chapter 9: Skeletal muscle in humans exhibits a day-night rhythm in lipid droplets and in the muscle lipidome
Chapter 10: Discussion and future prospects
Summary; Nederlandse samenvatting; Abbreviations; Authors' affiliations; Authors' contributions; List of publications; PhD portfolio; Acknowledgements; About the author
Propositions
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