15 Oct Fatty Liver At Least Partially Mediated By Epigenetic Influences
MedicalResearch.com Interview with:
Dr. Annette Schürmann
Annette Schürmann PhD
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE)
Nuthetal
Germany German Center for Diabetes Research (DZD
München-Neuherberg Germany
MedicalResearch.com: What is the background for this study?
Response: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern
of liver at two time points, at the age of 6 weeks, (the earlierst time
point to distiguish between those that respond to the diet (responder
mice) and those that did not (non-responders)), and at the age of 20
weeks. One transcript that was significantly reduced in the liver of
responder mice at both time points was Igfbp2. The reason for the
reduced expression was an elevated DNA-methylation at a position that is
conserved in the mouse and human sequence. The elevated DNA-methylation
of this specifc site in human was recently described to associate with
elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old
mice did not show differences in liver fat content between responder and
non-responder mice we conclude that the alteration of Igfbp2 expression
and DNA metyhlation occurs before the development of fatty liver.
Our data furthermore showed that the epigenetic inhibition of Igfbp2
expression was associated with elevated blood glucose and insulin
resistance but not with fatty liver.
MedicalResearch.com: What are the main findings?
Response: Our in vitro analysis showed a significant reduction of the reporter
activity by about 85% when the spefic site was methylated, giving direct
functional evidence that Igfbp2 expression is modulated by methylation.
Finally we analyzed human whole blood cells and demonstrated that
methylation of IGFBP2 was increased in obese men with impaired glucose
tolerance.
MedicalResearch.com: What should readers take away from your report?
Response: An early increase in body weight has an impact on later alterations in
the liver such as the development of a steatosis. Such alterations are
at least in part mediated via epigenetic alterations.
MedicalResearch.com: What recommendations do you have for future research as a result of this study?
Response: It will be of major interest to clarify which factors are responsible
for the DNA methylation at this particular site and at which stage it
actually occurs, in utero or at the early postnatal period.
It is also necessary to identify more epigenetic alterations that are induced
during early weight gain and to test how they can be reversed later in
life.
MedicalResearch.com: Thank you for your contribution to the MedicalResearch.com community.
Citation:
Hum Mol Genet. 2016 Apr 28. pii: ddw121. [Epub ahead of print]
Early hypermethylation of hepatic Igfbp2 results in its reduced expression preceding fatty liver in mice.
Kammel A1, Saussenthaler S1, Jähnert M1, Jonas W1, Stirm L2, Hoeflich A3, Staiger H2, Fritsche A2, Häring HU2, Joost HG1, Schürmann A4, Schwenk RW1.
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Last Updated on October 15, 2016 by Marie Benz MD FAAD