Metabolic adaptations through the PGC-1 alpha and SIRT1 pathways.
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-1 alpha 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-1 alpha and SIRT1 pathways might have important implications for comprehending metabolic and age-associated diseases.
Dana-Farber Cancer Institute, Harvard Medical School, One Jimmy Fund Way, Smith-936C, Boston, MA 02115, USA.
Joseph T
JT
Rodgers
Carles
C
Lerin
Zachary
Z
Gerhart-Hines
Pere
P
Puigserver
D000222:Adaptation, Physiological; D000818:Animals; D005947:Glucose / Q000378:metabolism; D050356:Lipid Metabolism; D010084:Oxidation-Reduction; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D016601:RNA-Binding Proteins; D051381:Rats; D056564:Sirtuin 1; D037761:Sirtuins / Q000378:metabolism*; D014157:Transcription Factors / Q000378:metabolism*
D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; C501429:Ppargc1a protein, rat; D016601:RNA-Binding Proteins; D014157:Transcription Factors; C488368:Sirt1 protein, rat; D056564:Sirtuin 1; D037761:Sirtuins; D005947:Glucose