title: Metabolic roles of PGC-1α and its implications for type 2 diabetes.
abstract: PGC-1α is a transcriptional coactivator expressed in brown adipose tissue, liver, pancreas, kidney, skeletal and cardiac muscles, and the brain. This review presents data illustrating how PGC-1α regulates metabolic adaptations and participates in the aetiology of type 2 diabetes (T2D). Studies in mice have shown that increased PGC-1α expression may be beneficial or deleterious, depending on the tissue: in adipose tissue, it promotes thermogenesis and thus protects against energy overload, such as seen in diabetes and obesity; in muscle, PGC-1α induces a change of phenotype towards oxidative metabolism. In contrast, its role is clearly deleterious in the liver and pancreas, where it induces hepatic glucose production and inhibits insulin secretion, changes that promote diabetes. Previous studies by our group have also demonstrated the role of PGC-1α in the fetal origins of T2D. Overexpression of PGC-1α in β cells during fetal life in mice is sufficient to induce β-cell dysfunction in adults, leading to glucose intolerance. PGC-1α also is associated with glucocorticoid receptors in repressing expression of Pdx1, a key β-cell transcription factor. In conclusion, PGC-1α participates in the onset of diabetes through regulation of major metabolic tissues. Yet, it may not represent a useful target for therapeutic strategies against diabetes as it exerts both beneficial and deleterious actions on glucose homoeostasis, and because PGC-1α modulation is involved in neurodegenerative diseases. However, its role in cellular adaptation shows that greater comprehension of PGC-1α actions is needed.
authors.affiliation: Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Pierre-et-Marie-Curie - Paris 6, UMR-S 1138, 75006 Paris, France; Université Paris Descartes, UMR-S 1138, 75006 Paris, France.
authors.forename: A
authors.initials: A
authors.lastname: Besseiche
authors.affiliation: Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Pierre-et-Marie-Curie - Paris 6, UMR-S 1138, 75006 Paris, France; Université Paris Descartes, UMR-S 1138, 75006 Paris, France; University Center of Diabetes and Complications in Lariboisière hospital, Université Paris-Diderot Paris-7, Public Assistance-Paris Hospitals, 75010 Paris, France.
authors.forename: J-P
authors.initials: JP
authors.lastname: Riveline
authors.affiliation: Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Pierre-et-Marie-Curie - Paris 6, UMR-S 1138, 75006 Paris, France; Université Paris Descartes, UMR-S 1138, 75006 Paris, France; University Center of Diabetes and Complications in Lariboisière hospital, Université Paris-Diderot Paris-7, Public Assistance-Paris Hospitals, 75010 Paris, France.
authors.forename: J-F
authors.initials: JF
authors.lastname: Gautier
authors.affiliation: Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Pierre-et-Marie-Curie - Paris 6, UMR-S 1138, 75006 Paris, France; Université Paris Descartes, UMR-S 1138, 75006 Paris, France.
authors.forename: B
authors.initials: B
authors.lastname: Bréant
authors.affiliation: Inserm, UMR-S 1138, Centre de Recherche des Cordeliers, 75006 Paris, France; Université Pierre-et-Marie-Curie - Paris 6, UMR-S 1138, 75006 Paris, France; Université Paris Descartes, UMR-S 1138, 75006 Paris, France. Electronic address: bertrand.blondeau@crc.jussieu.fr.
authors.forename: B
authors.initials: B
authors.lastname: Blondeau
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D003924:Diabetes Mellitus, Type 2 / Q000378:metabolism*; D004734:Energy Metabolism; D005943:Gluconeogenesis; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D007333:Insulin Resistance; D000078790:Insulin Secretion; D050417:Insulin-Secreting Cells / Q000378:metabolism*; D008099:Liver / Q000378:metabolism; D008954:Models, Biological; D018482:Muscle, Skeletal / Q000378:metabolism; D009928:Organ Specificity; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D022722:Thermogenesis; D014157:Transcription Factors / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*
chemical_list: D007328:Insulin; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D014157:Transcription Factors
keywords: Adipose tissue; Beta cells; Diabetes; Liver; Metabolism; PGC-1α