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Loss of mitochondrial protease ClpP protects mice from diet-induced obesity and insulin resistance.
- Source :
-
EMBO reports [EMBO Rep] 2018 Mar; Vol. 19 (3). Date of Electronic Publication: 2018 Feb 02. - Publication Year :
- 2018
-
Abstract
- Caseinolytic peptidase P (ClpP) is a mammalian quality control protease that is proposed to play an important role in the initiation of the mitochondrial unfolded protein response (UPR <superscript>mt</superscript> ), a retrograde signaling response that helps to maintain mitochondrial protein homeostasis. Mitochondrial dysfunction is associated with the development of metabolic disorders, and to understand the effect of a defective UPR <superscript>mt</superscript> on metabolism, ClpP knockout ( ClpP <superscript>-/-</superscript> ) mice were analyzed. ClpP <superscript>-/-</superscript> mice fed ad libitum have reduced adiposity and paradoxically improved insulin sensitivity. Absence of ClpP increased whole-body energy expenditure and markers of mitochondrial biogenesis are selectively up-regulated in the white adipose tissue (WAT) of ClpP <superscript>-/-</superscript> mice. When challenged with a metabolic stress such as high-fat diet, despite similar caloric intake, ClpP <superscript>-/-</superscript> mice are protected from diet-induced obesity, glucose intolerance, insulin resistance, and hepatic steatosis. Our results show that absence of ClpP triggers compensatory responses in mice and suggest that ClpP might be dispensable for mammalian UPR <superscript>mt</superscript> initiation. Thus, we made an unexpected finding that deficiency of ClpP in mice is metabolically beneficial.<br /> (© 2018 The Authors.)
- Subjects :
- Adipose Tissue, White metabolism
Adipose Tissue, White pathology
Animals
Diet, High-Fat adverse effects
Energy Metabolism genetics
Fatty Liver genetics
Fatty Liver metabolism
Fatty Liver pathology
Mice
Mice, Knockout
Mitochondria metabolism
Obesity metabolism
Obesity pathology
Unfolded Protein Response genetics
Endopeptidase Clp genetics
Insulin Resistance genetics
Mitochondria genetics
Obesity genetics
Subjects
Details
- Language :
- English
- ISSN :
- 1469-3178
- Volume :
- 19
- Issue :
- 3
- Database :
- MEDLINE
- Journal :
- EMBO reports
- Publication Type :
- Academic Journal
- Accession number :
- 29420235
- Full Text :
- https://doi.org/10.15252/embr.201745009