Download High fat diet induces metabolic disorder in the fruit fly Drosophila

High fat diet induces metabolic disorder in the fruit fly Drosophila melanogaster
Dissertation
zur Erlangung des Doktorgrades
der Mathematisch-Naturwissenschaftlichen Fakultät
der Christian-Albrechts-Universität zu Kiel
Vorgelegt von
Muhammad Naeem Faisal
aus Pakistan.
Kiel, 2014
Referent:
Prof Dr Thomas Roeder
Koreferent:
Prof. Dr Holger Heine
Tag der Mϋndlichen Prϋfung
25/02/2015
Zum Druck genehmigt:
Gez. Dekan:
Abstract
Different diets have a great impact on our health. HFD (High fat diet) have been linked to
epidemic development of various metabolic disorders. Manifestation of metabolic disorders
in the gut may be causally associated with several chronic diseases such as IBD, IBS, insulin
resistance and ultimately with cancer. Thus, the effects of HFD on various aspects of the gut
structure and physiology were studied using the fruit fly Drosophila melanogaster as a
model.
HFD induces substantial changes in the gut. Most importantly, it activates regeneration of the
intestinal epithelium. This nutritional intervention induced stem cells to divide and produce
enteroblasts with a small time delay. These enteroblasts develop into enterocytes and
enteroendorine cells. The structure of the intestine is different following HFD, as the number
of enteroendocrine cells was increased for longer periods indicating modified hormonal
system in response to this intervention. Structural changes in the intestine were seen even
after a short period of HFD. Apparently, the induction is triggered by HFD mediated
expressioj of the cytokine upd3. This induction appears to be meditaed via the JNK-pathway.
This induction is independent on the microbiota, as gnotobiotic animals show the same effect.
Nevertheless, HFD has a strong impact on the structure of the microbiota, meaning that the
number of bacteria is much higher following HFD.
In addition to the JNK-Upd3 axis, other signaling pathways are also activated in response to
HFD. Ca2+-signaling, indicated by the CaLexA system was chronically increased. Moreover,
the stress sensing pathway Nrf2 as well as the Notch-pathway were activated in enterocytes
in response to HFD. An activation of the intestinal innate immune response could not be
observed.
Physiologically, the consistency and structure of defecation products was changed in
response to HFD. The pH range was shifted towards more neutral values. Moreover, the
defecation rate was reduced, indicative for constipation and a reduced intestinal transit
process.
Taken together, HFD has a major impact on various aspects of the intestinal physiology,
including a long lasting modification of the intestinal hormonal system.