Dokument: Effects of circulating lipids on mitochondrial structure and function
| Titel: | Effects of circulating lipids on mitochondrial structure and function | |||||||
| Weiterer Titel: | Effekte von zirkulierenden Lipiden auf mitochondriale Struktur und Funktion | |||||||
| URL für Lesezeichen: | https://docserv.uni-duesseldorf.de/servlets/DocumentServlet?id=42287 | |||||||
| URN (NBN): | urn:nbn:de:hbz:061-20170515-111808-4 | |||||||
| Kollektion: | Dissertationen | |||||||
| Sprache: | Englisch | |||||||
| Dokumententyp: | Wissenschaftliche Abschlussarbeiten » Dissertation | |||||||
| Medientyp: | Text | |||||||
| Autor: | Schomburg, Ulrike [Autor] | |||||||
| Dateien: |
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| Beitragende: | Prof. Dr. Roden, Michael [Gutachter] PD Dr. Meissner, Thomas [Gutachter] | |||||||
| Stichwörter: | mitochondria lipid infusion free fatty acids insulin resistance | |||||||
| Dewey Dezimal-Klassifikation: | 600 Technik, Medizin, angewandte Wissenschaften » 610 Medizin und Gesundheit | |||||||
| Beschreibungen: | Insulinresistenz ist die vordergründige Pathologie des Diabetes mellitus Typ 2, einer lebensbedrohlichen Krankheit, die Millionen Menschen weltweit betrifft. Eine Erhöhung der freien Fettsäuren im Blut, inflammatorische Stoffwechselprozesse sowie eine Veränderung der mitochondrialen Funktion tragen zu Insulinresistenz bei oder können diese sogar verursachen.
Ziel der vorliegenden Studie war, den Effekt einer kurzzeitigen Erhöhung der freien Fettsäuren auf die mitochondriale Funktion und Morphologie zu überprüfen. Vor, während und im Anschluss an eine Lipidinfusion wurde gesunden Studienteilnehmer/innen eine Muskelbiopsie entnommen, um die Mitochondrienfunktion mittels hochauflösender Respirometrie und die zelluläre Mitochondrienmorphologie mittels Elektronenmikroskopie zu untersuchen. Eine kurzzeitige Lipiderhöhung resultierte in einer Erhöhung der muskulären Lipidansammlungen nach 2,5 und 4 h in Form von Fetttröpfchen. Dieser Effekt findet besondere Ausprägung in der regulatorischen Region, direkt unterhalb des Sarkolemms. Zudem wurde nach 4 h eine Abnahme der mitochondrialen Effektivität, repräsentiert durch die Respirations-Kontroll-Rate, beobachtet. Auch lag eine negative Korrelation zwischen der Größe der Mitochondrien und der respiratorischen Kapazität in Form der Respirations-Kontroll-Rate vor, was vermuten lässt, dass kleinere Mitochondrien effizienter in der Substratoxidation waren. Zwischen Mitochondrienfunktion und Fetttröpfchengehalt des Muskels zeigten sich keine signifikanten Korrelationen. Zusammenfassend wiesen die Ergebnisse auf einen direkten Zusammenhang zwischen erhöhten freien Fettsäuren und mitochondrialer Respiration hin. Kurzzeitige Erhöhung der Lipide steigerte direkt den muskulären Fetttröpfchengehalt, was auf dynamische und schnell reagierende Charakteristika dieses Kompartiments hindeutete. Der erhöhte Fetttröpfchengehalt des Muskels per se schien keinen direkten Einfluss auf die Mitochondrienfunktion zu haben, was darauf hinweist, dass der Beeinträchtigung der Funktion und Morphologie der Mitochondrien zusätzliche Signaltransduktionswege zugrunde liegen.Insulin resistance is the hallmark of type 2 diabetes mellitus, a condition with life threatening complications affecting millions of people worldwide. Increases in circulating free fatty acids, inflammatory pathways and abnormal features of mitochondrial function may contribute to or even cause insulin resistance. This study aimed at elucidating the effect of a short-term increase in circulating free fatty acids on mitochondrial function and morphology. Healthy volunteers received lipid infusions and underwent muscle biopsies for analyzing mitochondrial function by high resolution respirometry and sub-cellular morphology by electron microscopy. Short-term lipid elevation resulted in an increase in muscular lipid accumulation after 2.5 h and 4 h in the form of lipid droplets, in particular in the regulatory subsarcolemmal area. The respiratory control ratio was lowered after 4 h of lipid infusion, indicating impaired mitochondrial respiration. In addition, mitochondrial size correlated negatively with respiratory capacity as represented by the respiratory control ratio, suggesting that smaller mitochondria were more efficient in substrate oxidation. No correlations were found between mitochondrial functional parameters and lipid content. Taken together, these findings showed a direct interplay between circulating free fatty acids and mitochondrial respiration. Short-term lipid infusion directly increased muscular lipid content, which emphasized the dynamic and fast reacting nature of this compartment. Lipid droplet content per se did not affect mitochondrial function, which indicated that further metabolic pathways might underlie the functional impairment. | |||||||
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| Lizenz: |  Urheberrechtsschutz | |||||||
| Fachbereich / Einrichtung: | Medizinische Fakultät | |||||||
| Dokument erstellt am: | 15.05.2017 | |||||||
| Dateien geändert am: | 15.05.2017 | |||||||
| Promotionsantrag am: | 12.07.2016 | |||||||
| Datum der Promotion: | 02.05.2017 |
