Ablation of PGC-1beta results in defective mitochondrial activity,
thermogenesis, hepatic function, and cardiac performance.
Authors Lelliott CJ, Medina-Gomez G, Petrovic N, Kis A, Feldmann HM, Bjursell M, Parker
N, Curtis K, Campbell M, Hu P, Zhang D, Litwin SE, Zaha VG, Fountain KT, Boudina
S, Jimenez-Linan M, Blount M, Lopez M, Meirhaeghe A, Bohlooly-Y M, Storlien L,
Strömstedt M, Snaith M, Oresic M, Abel ED, Cannon B, Vidal-Puig A
Submitted By Submitted Externally on 3/4/2015
Status Published
Journal PLoS biology
Year 2006
Date Published 11/1/2006
Volume : Pages 4 : e369
PubMed Reference 17090215
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.

Investigators with authorship
E. Dale AbelUniversity of Iowa