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Curr Opin Lipidol. 2009 Apr;20(2):98-105. doi: 10.1097/MOL.0b013e328328d0a4.

PGC-1alpha, SIRT1 and AMPK, an energy sensing network that controls energy expenditure.

Author information

1
Ecole Polytechnique Fédérale de Lausanne, Lausanne, Switzerland.

Abstract

PURPOSE OF REVIEW:

Peroxisome proliferator-activated receptor gamma coactivator-1-alpha (PGC-1alpha) has been extensively described as a master regulator of mitochondrial biogenesis. However, PGC-1alpha activity is not constant and can be finely tuned in response to different metabolic situations. From this point of view, PGC-1alpha could be described as a mediator of the transcriptional outputs triggered by metabolic sensors, providing the idea that these sensors, together with PGC-1alpha, might be weaving a network controlling cellular energy expenditure. In this review, we will focus on how disorders such as type 2 diabetes and the metabolic syndrome might be related to an abnormal and improper function of this network.

RECENT FINDINGS:

Two metabolic sensors, AMP-activated protein kinase (AMPK) and SIRT1 have been described to directly affect PGC-1alpha activity through phosphorylation and deacetylation, respectively. Although the physiological relevance of these modifications and their molecular consequences are still largely unknown, recent insight from different in-vivo transgenic models clearly suggests that AMPK, SIRT1 and PGC-1alpha might act as an orchestrated network to improve metabolic fitness.

SUMMARY:

Metabolic sensors such as AMPK and SIRT1, gatekeepers of the activity of the master regulator of mitochondria, PGC-1alpha, are vital links in a regulatory network for metabolic homeostasis. Together, these players explain many of the beneficial effects of physical activity and dietary interventions in our battle against type 2 diabetes and related metabolic disorders. Hence, understanding the mechanisms by which they act could guide us to identify and improve preventive and therapeutic strategies for metabolic diseases.

PMID:
19276888
PMCID:
PMC3627054
DOI:
10.1097/MOL.0b013e328328d0a4
[Indexed for MEDLINE]
Free PMC Article
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