Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance. - Archive ouverte HAL Access content directly
Journal Articles PLoS Biology Year : 2006

Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance.

(1, 2) , (1) , (3) , (1) , (3) , (2) , (1) , (1) , (1) , (4) , (4) , (4) , (5) , (5) , (5) , (1) , (1) , (1) , (6) , (2) , (2) , (2) , (2) , (7) , (5) , (3) , (1, 8)
1
2
3
4
5
6
7
8
Mikael Bjursell
  • Function : Author
Ping Hu
  • Function : Author
Mohammad Bohlooly-y
  • Function : Author
Leonard Storlien
  • Function : Author
Maria Strömstedt
  • Function : Author
Michael Snaith
  • Function : Author
Matej Oresic

Abstract

The transcriptional coactivator peroxisome proliferator-activated receptor-gamma coactivator-1beta (PGC-1beta) has been implicated in important metabolic processes. A mouse lacking PGC-1beta (PGC1betaKO) was generated and phenotyped using physiological, molecular, and bioinformatic approaches. PGC1betaKO mice are generally viable and metabolically healthy. Using systems biology, we identified a general defect in the expression of genes involved in mitochondrial function and, specifically, the electron transport chain. This defect correlated with reduced mitochondrial volume fraction in soleus muscle and heart, but not brown adipose tissue (BAT). Under ambient temperature conditions, PGC-1beta ablation was partially compensated by up-regulation of PGC-1alpha in BAT and white adipose tissue (WAT) that lead to increased thermogenesis, reduced body weight, and reduced fat mass. Despite their decreased fat mass, PGC1betaKO mice had hypertrophic adipocytes in WAT. The thermogenic role of PGC-1beta was identified in thermoneutral and cold-adapted conditions by inadequate responses to norepinephrine injection. Furthermore, PGC1betaKO hearts showed a blunted chronotropic response to dobutamine stimulation, and isolated soleus muscle fibres from PGC1betaKO mice have impaired mitochondrial function. Lack of PGC-1beta also impaired hepatic lipid metabolism in response to acute high fat dietary loads, resulting in hepatic steatosis and reduced lipoprotein-associated triglyceride and cholesterol content. Altogether, our data suggest that PGC-1beta plays a general role in controlling basal mitochondrial function and also participates in tissue-specific adaptive responses during metabolic stress.
Fichier principal
Vignette du fichier
journal.pbio.0040369.pdf (511.51 Ko) Télécharger le fichier
Origin : Publisher files allowed on an open archive
Loading...

Dates and versions

inserm-00708271 , version 1 (14-06-2012)

Identifiers

Cite

Christopher J. Lelliott, Gema Medina-Gomez, Natasa Petrovic, Adrienn Kis, Helena M. Feldmann, et al.. Ablation of PGC-1beta results in defective mitochondrial activity, thermogenesis, hepatic function, and cardiac performance.. PLoS Biology, 2006, 4 (11), pp.e369. ⟨10.1371/journal.pbio.0040369⟩. ⟨inserm-00708271⟩
381 View
827 Download

Altmetric

Share

Gmail Facebook Twitter LinkedIn More