Towards a molecular understanding of adaptive thermogenesis.
Obesity results when energy intake exceeds energy expenditure. Naturally occurring genetic mutations, as well as ablative lesions, have shown that the brain regulates both aspects of energy balance and that abnormalities in energy expenditure contribute to the development of obesity. Energy can be expended by performing work or producing heat (thermogenesis). Adaptive thermogenesis, or the regulated production of heat, is influenced by environmental temperature and diet. Mitochondria, the organelles that convert food to carbon dioxide, water and ATP, are fundamental in mediating effects on energy dissipation. Recently, there have been significant advances in understanding the molecular regulation of energy expenditure in mitochondria and the mechanisms of transcriptional control of mitochondrial genes. Here we explore these developments in relation to classical physiological views of adaptive thermogenesis.
Lowell
B B
BB
Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, Massachusetts 02215, USA. blowell@caregroup.harvard.edu
Spiegelman
B M
BM
D000222:Adaptation, Physiological; D002001:Adipose Tissue, Brown / Q000502:physiology; D000818:Animals; D001831:Body Temperature / Q000235:genetics; D001921:Brain / Q000502:physiology; D002352:Carrier Proteins / Q000235:genetics / Q000502:physiology; D004268:DNA-Binding Proteins / Q000502:physiology; D004734:Energy Metabolism / Q000235:genetics / Q000502:physiology*; D005502:Food; D005544:Forecasting; D051268:GA-Binding Protein Transcription Factor; D005786:Gene Expression Regulation; D006801:Humans; D007473:Ion Channels; D008565:Membrane Proteins / Q000235:genetics / Q000502:physiology; D008928:Mitochondria / Q000235:genetics / Q000378:metabolism; D024101:Mitochondrial Proteins; D018482:Muscle, Skeletal / Q000502:physiology; D051264:Nuclear Respiratory Factors; D015534:Trans-Activators / Q000502:physiology; D014157:Transcription Factors / Q000502:physiology; D014158:Transcription, Genetic; D000071256:Uncoupling Protein 1
D002352:Carrier Proteins; D004268:DNA-Binding Proteins; D051268:GA-Binding Protein Transcription Factor; D007473:Ion Channels; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D051264:Nuclear Respiratory Factors; D015534:Trans-Activators; D014157:Transcription Factors; D000071256:Uncoupling Protein 1; C111264:peroxisome-proliferator-activated receptor-gamma coactivator-1