Submit Data |  Help |  Video Tutorials |  News |  Publications |  FTP Download |  REST API |  Citing RGD |  Contact   

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

Authors: Lelliott, Christopher J  Medina-Gomez, Gema  Petrovic, Natasa  Kis, Adrienn  Feldmann, Helena M  Bjursell, Mikael  Parker, Nadeene  Curtis, Keira  Campbell, Mark  Hu, Ping  Zhang, Dongfang  Litwin, Sheldon E  Zaha, Vlad G  Fountain, Kimberly T  Boudina, Sihem  Jimenez-Linan, Mercedes  Blount, Margaret  Lopez, Miguel  Meirhaeghe, Aline  Bohlooly-Y, Mohammad  Storlien, Leonard  Str√∂mstedt, Maria  Snaith, Michael  Oresic, Matej  Abel, E Dale  Cannon, Barbara  Vidal-Puig, Antonio 
Citation: Lelliott CJ, etal., PLoS Biol. 2006 Nov;4(11):e369. doi: 10.1371/journal.pbio.0040369.
Pubmed: (View Article at PubMed) PMID:17090215
DOI: Full-text: DOI:10.1371/journal.pbio.0040369

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.

Annotation

Gene Ontology Annotations
Objects Annotated

Additional Information

 
RGD Object Information
RGD ID: 13673853
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



NHLBI Logo

RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.