PuSH - Publication Server of Helmholtz Zentrum München: Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity.

Information

Clues to quality of journals

Open Access Policy of Helmholtz Association 2016

CC Licencences

Publication Metrics

Navigation

Home

Deutsch

Research

Advanced Search

Browse by ...

... HMGU-Authors/Consortia

... Organizational Structure

... Journal

... Publication Type

... Research Data

... Arbeitsgruppen

... Publication Year

Publication overview

Statistics

Statistics (last 5 years)

OA Publications

Publish

Submit Publication

Import publication from...

...EVA

Report missing publication

Highlights

Support & Contact

Contact persons

Help

Data protection

Helmholtz Open Science

JANE Journal Estimator

SHERPA/RoMEO

DOAJ

Export:

Text

Endnote (RIS) BIB

BibTeX

Jiang, S.* ; Yuan, T.* ; Rosenberger, F.A.* ; Mourier, A.* ; Dragano, N.R.V. ; Kremer, L.* ; Rubalcava-Gracia, D.* ; Hansen, F.M.* ; Borg, M.* ; Mennuni, M.* ; Filograna, R.* ; Alsina, D.* ; Misic, J.* ; Koolmeister, C.* ; Papadea, P.* ; Hrabě de Angelis, M. ; Ren, L.* ; Andersson, O.* ; Unger, A.* ; Bergbrede, T.* ; Di Lucrezia, R.* ; Wibom, R.* ; Zierath, J.R.* ; Krook, A.* ; Giavalisco, P.* ; Mann, M.* ; Larsson, N.G.*

Inhibition of mammalian mtDNA transcription acts paradoxically to reverse diet-induced hepatosteatosis and obesity.

Nat. Metab. 6, 1024-1035 (2024)

Publ. Version/Full Text

Research data

DOI

PMC

	Open Access Hybrid

Abstract
Metrics
Extra information

The oxidative phosphorylation system1 in mammalian mitochondria plays a key role in transducing energy from ingested nutrients2. Mitochondrial metabolism is dynamic and can be reprogrammed to support both catabolic and anabolic reactions, depending on physiological demands or disease states. Rewiring of mitochondrial metabolism is intricately linked to metabolic diseases and promotes tumour growth3–5. Here, we demonstrate that oral treatment with an inhibitor of mitochondrial transcription (IMT)6 shifts whole-animal metabolism towards fatty acid oxidation, which, in turn, leads to rapid normalization of body weight, reversal of hepatosteatosis and restoration of normal glucose tolerance in male mice on a high-fat diet. Paradoxically, the IMT treatment causes a severe reduction of oxidative phosphorylation capacity concomitant with marked upregulation of fatty acid oxidation in the liver, as determined by proteomics and metabolomics analyses. The IMT treatment leads to a marked reduction of complex I, the main dehydrogenase feeding electrons into the ubiquinone (Q) pool, whereas the levels of electron transfer flavoprotein dehydrogenase and other dehydrogenases connected to the Q pool are increased. This rewiring of metabolism caused by reduced mtDNA expression in the liver provides a principle for drug treatment of obesity and obesity-related pathology.

Impact Factor

Scopus SNIP

Altmetric

19.200

0.000