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Metabolic adaptations through the PGC‐1α and SIRT1 pathways
Author(s) -
Rodgers Joseph T.,
Lerin Carles,
Gerhart-Hines Zachary,
Puigserver Pere
Publication year - 2008
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/j.febslet.2007.11.034
Subject(s) - metabolic pathway , sirtuin , biology , acetylation , oxidative phosphorylation , nutrient sensing , function (biology) , sirtuin 1 , microbiology and biotechnology , calorie restriction , energy homeostasis , signal transduction , transcriptional regulation , enzyme , transcription factor , biochemistry , gene , downregulation and upregulation , endocrinology , receptor
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.