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EMBO Rep. 2018 May;19(5). pii: e45126. doi: 10.15252/embr.201745126. Epub 2018 Mar 27.

CLPP deficiency protects against metabolic syndrome but hinders adaptive thermogenesis.

Author information

1
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany.
2
Cologne Excellence Cluster on Cellular Stress Responses in Aging-Associated Diseases (CECAD) and Institute for Mitochondrial Diseases and Aging, Medical Faculty, University of Cologne, Cologne, Germany aleksandra.trifunovic@uk-koeln.de.
3
Center for Molecular Medicine (CMMC), University of Cologne, Cologne, Germany.

Abstract

Mitochondria are fundamental for cellular metabolism as they are both a source and a target of nutrient intermediates originating from converging metabolic pathways, and their role in the regulation of systemic metabolism is increasingly recognized. Thus, maintenance of mitochondrial homeostasis is indispensable for a functional energy metabolism of the whole organism. Here, we report that loss of the mitochondrial matrix protease CLPP results in a lean phenotype with improved glucose homeostasis. Whole-body CLPP-deficient mice are protected from diet-induced obesity and insulin resistance, which was not present in mouse models with either liver- or muscle-specific depletion of CLPP However, CLPP ablation also leads to a decline in brown adipocytes function leaving mice unable to cope with a cold-induced stress due to non-functional adaptive thermogenesis. These results demonstrate a critical role for CLPP in different metabolic stress conditions such as high-fat diet feeding and cold exposure providing tools to understand pathologies with deregulated Clpp expression and novel insights into therapeutic approaches against metabolic dysfunctions linked to mitochondrial diseases.

KEYWORDS:

VLCAD ; CLPP deficiency; fatty acid oxidation; metabolism; thermogenesis

PMID:
29588285
PMCID:
PMC5934779
[Available on 2019-05-01]
DOI:
10.15252/embr.201745126

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