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dc.contributor.author
Jambor de Sousa, Ulrike Leonore
dc.contributor.supervisor
Geary, Nori
dc.contributor.supervisor
Langhans, Wolfgang
dc.date.accessioned
2017-08-15T08:10:43Z
dc.date.available
2017-06-10T00:48:38Z
dc.date.available
2017-08-15T08:10:43Z
dc.date.issued
2005
dc.identifier.uri
http://hdl.handle.net/20.500.11850/49079
dc.identifier.doi
10.3929/ethz-a-005062037
dc.description.abstract
The major hypothesis for the metabolic control of eating posits that eating is inversely related to the rate of fuel oxidation. In line with this idea, blockade of fatty acidoxidation (FAO) by peripheral administration of inhibitors of FAO stimulates feeding in many species, including humans. Even though it is not proven yet that the liver is involved in this feeding-stimulatoryeffect, several findings suggest that this is the case. Yet, whether an increased hepatic FAO inhibits feeding is unknown. Therefore, the central aim of this thesis was to determine whether enhanced hepatic FAO reduces food intake. In the first study, we infused the long chain fatty acid (LCFA) oleic acid (OA) and the mediumchain fatty acid (MCFA)caprylic acid (CA) into the hepatic portal vein (HPV) of male rats to assess whether HPV infusion of these two fatty acids reducesfood intake and whether their relative efficacy differs. MCFA are oxidized faster in the liver because they are absorbed directly into the hepatic portal vein and because they can enter the mitochondria independent of the enzyme carnitine-palmitoyl-transferase1 (CPT 1). Hence, we hypothesized that HPV CA will have a greater feeding-inhibitorypotency than HPV OA. This hypothesis was not supported. Rather, 6-h HPV infusion of 14 ^ig/minOA produced a robust inhibition of feeding, whereas a dose of CA that was 14 times larger (200 jag/min) than that of OA failed to have any effect on feeding. OA (14 ^ig/min) and an 80-fold greater dose of CA (1100 ^ig/min) inhibited feeding similarly. These findings indicate that increased hepatic FAO is unlikely to be responsible for the feedinginhibitory effect of HPV OA. The plasma concentrations of the liver enzymes yglutamyltransferase (-^GT) and alanine aminotransferase (ALT), the pro-inflammatory cytokines interleukin-6 (IL-6) and tumor necrosis factor-a (TNF-a), and the stress hormone corticosterone (Cort) all remained in the physiological ränge after HPV OA, indicating that liver toxicitywas also not the cause of HPV OA's potent effect on feeding. In the second study, 90-min, dark onset HPV infusion of CA (2.3 mg/min) after 18-h food-deprivation reduced the size of the first meal about 40% and reduced 24-h food intake by about 13%. The feeding-inhibitoryeffect of CA originated in the liver because identical infusions of CA into the vena cava did not affect food intake. The postprandial decreases in plasma free fatty acids (FFA) and ß-hydroxybutyrate (BHB) were attenuated in HPV CA-treated rats, indicating that hepatic FAO was increased in HPV CA infused rats relative to controls. This is consistent with the hypothesis that an increased hepatic FAO reduces food intake, but does not prove that there is a causal link between increased hepatic FAO and reduced food intake. Further the finding that animals started eating after food deprivation although their hepatic FAO was enhanced clearly demonstratesthat beside hepatic FAO other mechanismsmust be involved in the regulation of food intake. A conditioned taste aversion test was done in separate rats. Some, but not all, rats displayed aversions to saccharine paired with HPV CA infusions, but there was no significant association between the feeding-inhibitoryeffect of CA on the conditioning day and saccharine intake on the test day. Plasma concentrations of IL-6, TNF-oc, y-GT, ALT and Cort stayed at basal levels. Taken together, these data suggest that the feeding-inhibitory effect of CA was not due only to aversion or toxicity. In the third study we wanted to develop an alternative approach to test the hypothesis that increased hepatic FAO can inhibit feeding behavior. We used transgenic methods to increase the expression of CPT 1alpha, an enzyme which catalyzes the rate limiting step of hepatic FAO, in the 293T human embryonic kidney cell line. Activation of the CPTla transgenethrough an inducible tet-on gene expression system increased mitochondrial long-chain fatty acid oxidation about 6-fold. Increasing palmitic acid concentration, however, decreased viability of CPT1alpha over-expressing cells, and CPT1alpha over-expression increased cell death. These data encourage the use of this transgenic system for future in-vivo studies of the roles of fatty acid oxidation in the control of metabolism and energy balance.
en_US
dc.format
application/pdf
dc.language.iso
en
en_US
dc.publisher
ETH
en_US
dc.rights.uri
http://rightsstatements.org/page/InC-NC/1.0/
dc.subject
NUTRITIONAL REQUIREMENTS + FOOD QUANTITY + FOOD RATION (NUTRITIONAL PHYSIOLOGY)
en_US
dc.subject
FETTSÄURENMETABOLISMUS
en_US
dc.subject
FETTSÄUREOXIDATION (METABOLISMUS)
en_US
dc.subject
ESSEN + TRINKEN + KAUEN + NAHRUNGSAUFNAHME (PHYSIOLOGIE)
en_US
dc.subject
EATING + DRINKING + MASTICATION + FOOD INGESTION (PHYSIOLOGY)
en_US
dc.subject
NAHRUNGSBEDARF + NAHRUNGSMENGE + NAHRUNGSRATION (ERNÄHRUNGSPHYSIOLOGIE)
en_US
dc.subject
FATTY ACID METABOLISM
en_US
dc.subject
FATTY ACID OXIDATION (METABOLISM)
en_US
dc.title
Fatty acid metabolism and control of food intake
en_US
dc.type
Doctoral Thesis
dc.rights.license
In Copyright - Non-Commercial Use Permitted
ethz.size
94 p.
en_US
ethz.code.ddc
DDC - DDC::6 - Technology, medicine and applied sciences::660 - Chemical engineering
en_US
ethz.code.ddc
DDC - DDC::6 - Technology, medicine and applied sciences::610 - Medical sciences, medicine
en_US
ethz.identifier.diss
16153
en_US
ethz.identifier.nebis
005062037
ethz.publication.place
Zürich
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::03274 - Langhans, Wolfgang (emeritus)
en_US
ethz.leitzahl
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02703 - Institut für Agrarwissenschaften / Institute of Agricultural Sciences::03428 - Kreuzer, Michael (emeritus) / Kreuzer, Michael (emeritus)
en_US
ethz.leitzahl.certified
ETH Zürich::00002 - ETH Zürich::00012 - Lehre und Forschung::00007 - Departemente::02350 - Dep. Umweltsystemwissenschaften / Dep. of Environmental Systems Science::02703 - Institut für Agrarwissenschaften / Institute of Agricultural Sciences::03428 - Kreuzer, Michael (emeritus) / Kreuzer, Michael (emeritus)
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::03274 - Langhans, Wolfgang (emeritus)
ethz.date.deposited
2017-06-10T00:49:06Z
ethz.source
ECOL
ethz.source
ECIT
ethz.identifier.importid
imp59366a903c4c160568
ethz.identifier.importid
imp59364f368e98586671
ethz.ecolpid
eth:28144
ethz.ecitpid
pub:80724
ethz.eth
yes
en_US
ethz.availability
Open access
en_US
ethz.rosetta.installDate
2017-07-26T20:18:49Z
ethz.rosetta.lastUpdated
2022-03-28T17:23:41Z
ethz.rosetta.versionExported
true
ethz.COinS
ctx_ver=Z39.88-2004&rft_val_fmt=info:ofi/fmt:kev:mtx:journal&rft.atitle=Fatty%20acid%20metabolism%20and%20control%20of%20food%20intake&rft.date=2005&rft.au=Jambor%20de%20Sousa,%20Ulrike%20Leonore&rft.genre=unknown&rft.btitle=Fatty%20acid%20metabolism%20and%20control%20of%20food%20intake
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