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PGC-1β: A Co-activator That Sets the Tone for Both Basal and Stress-Stimulated Mitochondrial Activity

  • Christopher J. Lelliott
  • Antonio Vidal-Puig
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 646)

The peroxisomal proliferator-activated receptor-gamma coactiva-tor (PGC) family of transcriptional coactivators are central regulators of a wide-range of metabolic processes, which combine to control whole-body homeostasis. However, the specific function of each PGC in a tissue and pathway-specific context is only now being elucidated. In order to define the specific roles of PGC-1β, we generated a mouse lacking this gene and studied its phenotype using a combination of physiological experiments, guided by a systems biology approach. We found that despite the predicted obese phenotype, PGC1βKO were leaner than wild-type and had elevated energy expenditure in the resting state, probably due to upregulation of a wide-range of oxidative and fuel-handling genes in the brown adipose tissue (BAT), including PGC family member PGC-1α. Nonetheless, we identified that PGC-1β ablation results in a global reduction in oxidative phosphorylation and electron transport chain genes and this translates into mitochondrial dysfunction in selected tissues. PGC1βKO mice also demonstrate blunted responses to physiological stresses such as cold exposure in BAT, adrenergic stimulation in BAT and heart and acute dietary lipid loads in liver. In summary, while lack of PGC-1β is not deleterious, it is essential for the normal expression of mitochondrial metabolic genes and for the optimal ability to handle physiological stresses.

Keywords

PGC mitochondria brown adipose tissue knock-out metabolism 

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Copyright information

© Springer Science + Business Media B.V 2009

Authors and Affiliations

  1. 1.Department of Clinical BiochemistryUniversity of CambridgeCambridgeUK
  2. 2.AstraZeneca R&DSweden

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