Leiden University Scholarly Publications

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Wijngaarden, M.A. (2015)

Metabolic and endocrine adaptations to fasting in lean and obese individuals

Doctoral Thesis
In this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was impaired in obese individuals. At baseline, mitochondrial protein content in skeletal muscle of obese subjects was significantly reduced compared to lean individuals. We assessed the neuronal response to fasting by fMRI scanning. We found a different neuronal response to fasting between lean and obese individuals in terms of functional connectivity between the hypothalamus and respectively the dACC and insula. Since these regions are part of the saliency network, these differences may reflect distinct perception of calorie imbalance between lean and obese subjects. The effects of fasting on sympathetic tone (estimated by heart rate variability) were studied. Our data suggests that fasting decreases sympathetic tone in lean subjects, whereas it increases sympathetic activity in obese...Show moreIn this thesis we examined several effects of fasting in lean and obese individuals. As expected, both the hormonal response as well as the metabolic shift from glucose towards lipid oxidation was impaired in obese individuals. At baseline, mitochondrial protein content in skeletal muscle of obese subjects was significantly reduced compared to lean individuals. We assessed the neuronal response to fasting by fMRI scanning. We found a different neuronal response to fasting between lean and obese individuals in terms of functional connectivity between the hypothalamus and respectively the dACC and insula. Since these regions are part of the saliency network, these differences may reflect distinct perception of calorie imbalance between lean and obese subjects. The effects of fasting on sympathetic tone (estimated by heart rate variability) were studied. Our data suggests that fasting decreases sympathetic tone in lean subjects, whereas it increases sympathetic activity in obese individuals. Weight loss in obese individuals increased HRV parameters that reflect the postprandial sympathetic tone. Finally, we studied the effects of fasting in the presence and absence of food-odors since this has been shown to reduce the fasting-induced increase in life span in fruit flies __ no differences were found in our human subjects.Show less
Biopsies
Endocrinology
Neuroendocrinology
Skeletal muscle
Functional MRI
Starvation
Fasting
Obesity
All authors
Wijngaarden, M.A.
Supervisor
Pijl, H.; Willems Van Dijk, K.
Co-supervisor
Guigas, B.
Qualification
Doctor (dr.)
Awarding Institution
Leiden University Medical Center (LUMC), Leiden University
Date
2015-03-26
ISBN (print)
9789491098796

Funding

Sponsorship
The Center for Medical Systems Biology (CMSB), within the framework of the Netherlands GenomicsInitiative (NGI/NOW). Boehringer Ingelheim Goodlife Pharma Ipsen Farmaceutica Novartis Pharma B.V. Novo Nordisk B.V., Pfizer BV