Christian Riehle  

Home Institution
Albert-Ludwigs-Universität Freiburg i. Br.

Host Institution
Division of Endocrinology, Metabolism and DiabetesProgram in Human Molecular Biology and GeneticsUniversity of Utah School of Medicine, Salt Lake City, UT
Research Mentor: Evan Dale Abel, MD, PhD

E-Mail: ch.riehle@gmx.de
Research Topic
see Abstract
Personal Reactions to the U.S. Experience
One of the biggest differences between the US and Europe, especially Germany, I realized during my stay in Salt Lake City is - No, it is not the gas prices as you could think and it is not the fact that everybody takes the car to work, even if they live half a mile away. And it is not the way some Americans decorate their homes in the time before Christmas with monumental sculptures of Santa Claus and his reindeer riding up in the sky. And it is also not the fact that it may take you up to 30 minutes standing in the waiting line at the grocery store, as everyone in front of you chats with the cashier. – I think the biggest difference is the way the people think in the US. People seem to be much more optimistic and curious about new things and possibilities than people in our home country. In my opinion, that’s the reason why some of them just give it a try and succeed, while someone else from Germany might still think about the consequences. That’s the difference between a warrior and a worrier!
Greatest Difficulties Encountered
Moving into an unfurnished apartment and organizing some furniture without having a car.
Helpful Hints for Future Students
- Plan your visa application well in advance.
- Contact a BMEP student for further questions.
- Attend the BMEP-Forum in Farmington.
- Try to find a place to live in advance, before you arrive in the US.
- Check www.bild.de and you know within 2 minutes what’s going on in Germany.
- Be a warrior, not a worrier!

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Abstract on Research Topic

Role of PGC-1β in the Regulation of Myocardial Mitochondrial Function
Authors:
Christian Riehle(1), Vlad G. Zaha(1), Adam R. Wende(1), Ping Hu(1), Christopher Lelliot(2), Antonio Vidal-Puig(2), E. Dale Abel(1)

(1)Division of Endocrinology, Metabolism and Diabetes, Program in Human Molecular Biology and Genetics, University of Utah School of Medicine, Salt Lake City, UT, USA
(2)Department of Clinical Biochemistry, University of Cambridge, Cambridge, United Kingdom

Institution:
University of Utah, Salt Lake City, UT

Materials and Methods:
The transcriptional coactivators PGC-1a and PGC-1b regulate mitochondrial (MITO) biogenesis and fatty acid oxidation (FAO) genes. KO of PGC-1b resulted in decreased MITO volume and O2 consumption in skeletal muscle, however the impact on cardiac MITO function is unknown. Hearts predominantly metabolize FAs, however following pressure-overload hypertrophy there is a reduction in FAO and increased glycolysis that parallels a reduction in PGC-1a expression. We therefore also sought to determine the role of PGC-1b in the MITO adaptations of the heart to pressure-overload cardiac hypertrophy, induced by transverse aortic banding (AB). In non-stressed hearts maximal ADP-stimulated MITO oxygen consumption (state 3 respiration) in saponin permeabilized cardiac fibers, with pyruvate as a substrate were unchanged in PGC-1b-/- hearts (18.8 ±0.7 nmolO2/min/mg dw) relative to wildtype (WT) controls (19.4±1.0). By contrast, palmitoyl carnitine (PC) supported state 3 respirations were reduced (WT vs. KO: 16.4±0.4 vs. 11.2±0.6, p<0.01). 8-weeks following AB there was significant hypertrophy in both control (WT) and PGC-1b-/- (KO) mice (heart to tibia-length-ratio (HW/TL) 1.90±0.22 fold increase in WT and 1.63±0.11 fold in KO, p<0.01, n=12). Relative to non-banded hearts, AB reduced MITO state 3 respirations by 15% (p<0.05) and 32% (p<0.05) with pyruvate and PC respectively as substrates in WT hearts. In KO hearts, AB had no further effect on PC supported MITO respirations, but reduced pyruvate respirations by 21% (p<0.05) relative to non-banded KO hearts. AB reduced PGC-1a expression in WT and KO hearts and AB had no effect on PGC-1b expression in WT. In WT hearts, AB was associated with uniform reductions in FAO and OXPHOS gene expression (between 20-50%). In PGC-1b-/- OXPHOS gene expression was uniformly reduced in non-banded hearts (between 25-40%), but only a subset of genes (cox5b, cytochrome c oxidase and Ndufa9) were further reduced by AB. A subset of FAO genes were reduced in expression in non-banded KO hearts (MCAD, Acate and carnitine acyl/carnitine translocase), and these genes were distinct from those whose expression was only reduced in KO hearts after AB (UCP2, UCP3 and Hadh).

Conclusions:
These studies confirm an important role for PGC-1b in the regulation of MITO FA utilization in the heart but also suggest potentially non overlapping roles for PGC-1b versus PGC-1a in the MITO adaptations to pressure overload cardiac hypertrophy.