The role of transcriptional regulators in central control of appetite and body weight.
Individuals who live in industrialized countries often eat a calorie-rich diet and perform little physical activity. These habits are thought to be critical contributors to the rapidly rising incidence of obesity, a condition that affects hundreds of millions of people worldwide. High-calorie intake alters metabolic-sensing pathways in central nervous system neurons, and these changes have pathogenic roles in the development of obesity. This review aims to summarize our current knowledge about the neuronal populations (the central melanocortin system in particular) and transcriptional regulators, including STAT3 and FOXO1, that are involved in the maintenance of normal body weight. We describe the interactions between these transcriptional factors and their target genes, which encode the main appetite-regulating neuropeptides (agouti-related peptide and alpha-melanocyte-stimulating hormone). We discuss the transcriptional co-activator PGC-1-alpha and the supposed metabolic-sensor protein SIRT1, and their potential roles as targets for novel antiobesity medications.
Coppari
Roberto
R
Department of Internal Medicine, Division of Hypothalamic Research, University of Texas Southwestern Medical Center, Dallas, TX 75390-9077, USA. roberto.coppari@utsouthwestern.edu
Ramadori
Giorgio
G
Elmquist
Joel K
JK
D001066:Appetite / Q000235:genetics / Q000502:physiology*; D001835:Body Weight / Q000235:genetics / Q000502:physiology*; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D006360:Heat-Shock Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D008954:Models, Biological; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D050796:STAT3 Transcription Factor / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D056564:Sirtuin 1; D037761:Sirtuins / Q000235:genetics / Q000378:metabolism / Q000502:physiology; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism / Q000502:physiology*
C085126:FOXO1 protein, human; D000071161:Forkhead Box Protein O1; D051858:Forkhead Transcription Factors; D006360:Heat-Shock Proteins; C486497:PPARGC1A protein, human; D000071248:Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; D014157:Transcription Factors; C447939:SIRT1 protein, human; D056564:Sirtuin 1; D037761:Sirtuins