TY - JOUR

T1 - Metabolic adaptations through the PGC-1α and SIRT1 pathways

AU - Rodgers, Joseph T.

AU - Lerin, Carles

AU - Gerhart-Hines, Zachary

AU - Puigserver, Pere

N1 - Funding Information: We thank other members of the Puigserver laboratory for insightful discussions and comments on this manuscript. Work in this laboratory is supported in part by an Ellison Medical Foundation New Scholar Award, the American Diabetes Association, the U.S. Department of Defense, and National Institutes of Health Grant R01 DK069966 (to P.P.). Due to space limitations, we apologize for not including additional information or references that are related to studies discussed in this review.

PY - 2008/1/9

Y1 - 2008/1/9

N2 - Energy homeostasis in mammals is achieved through tight regulation of tissue-specific metabolic pathways that become dysregulated in metabolic diseases including diabetes and obesity. At the molecular level, main nutrient and hormonal signaling pathways impinge on expression of genes encoding for metabolic enzymes. Among the major components of this transcriptional circuitry are the PGC-1α transcriptional complexes. An important regulatory mechanism of this complex is through acetylation and SIRT1-mediated lysine de-acetylation under low nutrient conditions. Activation of SIRT1 can mimic several metabolic aspects of calorie restriction that target selective nutrient utilization and mitochondrial oxidative function to regulate energy balance. Thus, understanding the PGC-1α and SIRT1 pathways might have important implications for comprehending metabolic and age-associated diseases.

AB - Energy homeostasis in mammals is achieved through tight regulation of tissue-specific metabolic pathways that become dysregulated in metabolic diseases including diabetes and obesity. At the molecular level, main nutrient and hormonal signaling pathways impinge on expression of genes encoding for metabolic enzymes. Among the major components of this transcriptional circuitry are the PGC-1α transcriptional complexes. An important regulatory mechanism of this complex is through acetylation and SIRT1-mediated lysine de-acetylation under low nutrient conditions. Activation of SIRT1 can mimic several metabolic aspects of calorie restriction that target selective nutrient utilization and mitochondrial oxidative function to regulate energy balance. Thus, understanding the PGC-1α and SIRT1 pathways might have important implications for comprehending metabolic and age-associated diseases.

KW - Aging

KW - Glucose metabolism

KW - Lipid metabolism

KW - Mitochondrial oxidation

KW - PGC-1α

KW - SIRT1

UR - http://www.scopus.com/inward/record.url?scp=37349110355&partnerID=8YFLogxK

U2 - 10.1016/j.febslet.2007.11.034

DO - 10.1016/j.febslet.2007.11.034

M3 - Journal article

C2 - 18036349

AN - SCOPUS:37349110355

VL - 582

SP - 46

EP - 53

JO - F E B S Letters

JF - F E B S Letters

SN - 0014-5793

IS - 1

ER -