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dc.contributor.author
Straub, Leon
dc.contributor.supervisor
Wolfrum, Christian
dc.contributor.supervisor
Ristow, Michael
dc.contributor.supervisor
Heeren, Jörg
dc.date.accessioned
2020-01-06T14:34:15Z
dc.date.available
2017-12-19T10:43:32Z
dc.date.available
2017-12-19T11:23:00Z
dc.date.available
2017-12-19T11:25:33Z
dc.date.available
2020-01-06T14:34:15Z
dc.date.issued
2017
dc.identifier.uri
http://hdl.handle.net/20.500.11850/222622
dc.identifier.doi
10.3929/ethz-b-000222622
dc.description.abstract
As of 2014, the World Health Organization estimated 1.9 billion overweight people, of which 600 million were obese. Yearly, 3.4 million people die from overweight and obesity, when excluding the effects of associated diseases. Overweight is one of the strongest risk factors for development of Type 2 Diabetes Mellitus (T2DM), of which the treatment accounts for 12 percent of world wide total health expenditure (2015). The individual tragedies that obesity causes are even worse than the estimated world wide health costs of 673 billion dollars. Since numbers of obesity incidences still rise despite of dietary guidelines being formulated and implemented, further basic research on adipose tissue and diabetes is urgently required. Scientists continue to search for a causal link between obesity and the development of T2DM. Besides literature reviewing the role of a certain type of adipose tissue in mediating the anti-obesity effect of fibroblast growth factor 21 (FGF21), this thesis is about the adipose tissue organ's plasticity and its role in the development of T2DM. First, I addressed very basic scientific questions about the adipose organ through the quantification of adipocyte cell numbers and their character by applying a newly developed quantitative polymerase chain reaction based method. Using this tool, we could establish and improve the tamoxifen protocol of Adipoq-tracer and Ucp1-tracer-depleter mouse models. Secondly, we aimed to prove that induction of adipose tissue specific insulin resistance causes development of T2DM. For this purpose we generated a CreERT2-loxP genetic mouse model of tamoxifen inducible fat-specific Insulin receptor knockout (iFIRKO). Inducing insulin resistance in lean and obese adult mice, we found a temporary development of T2DM that was reversed already 3 weeks after the knockout, but adipose tissue mass remained reduced. iFIRKO mice are long term protected from the obesogenic effect of high fat diet. Furthermore, we prevented development of hyperphagia and polydipsia in iFIRKO mice with two antioxidants Apocynin and N-acetylcystein (Nac) and strongly reduced hyperglycemia by Apocynin alone. Finally, we could confirm food intake reduction and blood glucose lowering capacity of Apocynin and Nac in the hyperphagic obesity model of Leptin knockout mice. We conclude that insulin resistance in adipose tissue can protect from obesity, but also causes T2DM. This development of T2DM can be targeted downstream of the Leptin Receptor through the use of Apocynin and Nac.
en_US
dc.format
application/pdf
dc.language.iso
en
en_US
dc.publisher
ETH Zurich
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.subject
Lipoatrophy
en_US
dc.subject
Adipose Tissue
en_US
dc.subject
Fat
en_US
dc.subject
Insulin Resistance
en_US
dc.subject
Diabetes
en_US
dc.subject
T2DM
en_US
dc.subject
T2D
en_US
dc.subject
Obesity
en_US
dc.subject
Insulin Receptor
en_US
dc.subject
Antioxidants
en_US
dc.subject
Apocynin
en_US
dc.subject
N-acetylcystein
en_US
dc.subject
Hyperphagia
en_US
dc.subject
FGF21
en_US
dc.subject
Ucp1
en_US
dc.subject
iFIRKO
en_US
dc.subject
fat-specific insulin receptor knockout
en_US
dc.subject
leptin
en_US
dc.subject
brown adipose tissue
en_US
dc.subject
white adipose tissue
en_US
dc.subject
WAT
en_US
dc.subject
BAT
en_US
dc.title
Adipose Tissue Biology and the Development of Type 2 Diabetes Mellitus
en_US
dc.type
Doctoral Thesis
dc.rights.license
In Copyright - Non-Commercial Use Permitted
dc.date.published
2017-12-19
ethz.size
93 p.
en_US
ethz.code.ddc
DDC - DDC::6 - Technology, medicine and applied sciences::610 - Medical sciences, medicine
ethz.identifier.diss
24765
en_US
ethz.publication.place
Zurich
en_US
ethz.publication.status
published
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02070 - Dep. Gesundheitswiss. und Technologie / Dep. of Health Sciences and Technology::02701 - Inst.f. Lebensmittelwiss.,Ernährung,Ges. / Institute of Food, Nutrition, and Health::03819 - Wolfrum, Christian / Wolfrum, Christian
en_US
ethz.date.deposited
2017-12-19T10:43:32Z
ethz.source
FORM
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.date.embargoend
2019-12-19
ethz.rosetta.installDate
2017-12-19T11:23:03Z
ethz.rosetta.lastUpdated
2021-02-15T07:10:50Z
ethz.rosetta.versionExported
true
ethz.COinS
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