The metabolic, neural, and behavioral outcomes of intermittent caloric deprivation in diet-induced obese mice
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Gotthardt, Juliet D..
The metabolic, neural, and behavioral outcomes of intermittent caloric deprivation in diet-induced obese mice. Retrieved from
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TitleThe metabolic, neural, and behavioral outcomes of intermittent caloric deprivation in diet-induced obese mice
Date Created2017
Other Date2017-10 (degree)
Extent1 online resource (xii, 128 p. : ill.)
DescriptionAlternate day intermittent fasting (IMF) has recently gained traction as a popular dietary strategy to produce weight loss in obese individuals. In this dissertation, we investigate the metabolic, neural, and behavioral effects of IMF to further elucidate the mechanisms driving sustained weight loss. To produce diet-induced obesity, male mice were placed on an ad libitum 45% high fat diet (HFD) for 8 weeks. Animals were subsequently placed on one of four experimental diets for 4 weeks as follows: continuation of ad libitum HFD, IMF of HFD (IMF-HFD), switched to a 10% low fat diet (LFD), or IMF of LFD (IMF-LFD). IMF-HFD and IMF-LFD animals consistently lost body weight, 13-27% and 18-32% reduction respectively, compared to HFD animals. Oral glucose tolerance AUC was lower in IMF-HFD (~50%) while insulin tolerance AUC was reduced in IMF-HFD, LFD, and IMF-LFD (~22-42%). Norepinephrine content in the anterior portion of the medial hypothalamus was higher in IMF animals compared to HFD and LFD groups while only IMF-LFD was higher in the posterior portion. Furthermore, relative Npy gene expression was higher in IMF-HFD and IMF-LFD compared to HFD and LFD mice. Neural activation of hypothalamic NPY neurons was measured following an acute glucoprivic challenge with 2-deoxy-D-glucose (2-DG). In the paraventricular nucleus, there was a significant increase in neural activation following 2-DG administration, but there were no differences between treatment groups given 2-DG. There were no differences in the arcuate nucleus nor were there differences in NPY/c-Fos double-labeling in either region. A subset of animals, which also including groups pair-fed to IMF animals (PF-HFD and PF-LFD) were used to evaluate feeding behavior during IMF and after 6 weeks of HFD re-feeding. At the end of the diet period, the first meal of the last feeding day was recorded. The first meal duration was longer in LFD and IMF-LFD mice compared to HFD. Additionally, IMF-HFD had a greater first meal size and faster rate of consumption than HFD animals. Average meal duration at the end of the diet period was longer in the low-fat diet groups compared to the HFD-groups. There were no meal pattern differences at the end of the HFD re-feeding period. In summary, these results suggest that IMF is an effective strategy for weight loss that produces specific alterations in hypothalamic signaling and that meal patterns are only transiently altered in diet-induced obese male mice.
NotePh.D.
NoteIncludes bibliographical references
Noteby Juliet D. Gotthardt
Genretheses, ETD doctoral
Languageeng
CollectionSchool of Graduate Studies Electronic Theses and Dissertations
Organization NameRutgers, The State University of New Jersey
RightsThe author owns the copyright to this work.
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