metabolic clock and control mechanisms

The activities of our bodies follow cycles of repeated oscillations, examples are the sleep-wake cycle, the feeding rhythm and variations in body temperature and hormonal levels. The anatomical centre of the mammalian circadian clock lies within the suprachiasmatic nucleus region of the brain in the anterior hypothalamus.
Many of these cyclic oscillations are circadian (of around 24-hour periodicity), and are controlled by an interplay of numerous molecular factors which ensure the accuracy of the ‘body clock’. The body clock is , organized in complex feedback loops that involve gene transcription and the events that follow it.
The peripheral tissues of many creatures contain independent pacemakers involved in a ‘synchronization web’ that coordinates timing in all the tissues. The transcription of at least 10% of all cellular genes oscillates in a circadian manner indicates how the circadian transcriptional mechanisms influence a wide array of cellular functions.
PGC-1α is a transcriptional coactivator with an essential role in the maintenance of glucose, lipid and energy homeostasis.. It is highly responsive to a variety of environmental cues, temperature, nutritional status and physical activity. Liu and colleagues have shown that the transcriptional regulator PGC-1α is a key factor in the molecular pathways in the circadian control of energy metabolism,.
Several genes contribute to the regulation of the circadian rhythm, including Clock, Bmall, Per. Cry and Rev-erba. The findings of Liu et al showed in Nature that PGC-l α, has a central role in connecting the expression and function of these circadian clock genes in the regulation of energy metabolism, including gluconeogenesis (the synthesis of glucose from non-.sugar substrates), oxidative phosphorylation, oxidation of fatty acids and the biosynthesis of haem.
This function of PGC-l α seems to be mediated by nuclear receptors, such as ROR α, and other, unidentified, transcription factors.
Grimaldi and Sassone-Corsi (2007) Metabolic clockwork Nature vol 447 pp 386-7
Liu et al (2007 ) Transcriptional coactivator PGC-1a integrates the mammalian clock and energy metabolism ( 2007) Nature vol 447 pp 477-81

Martin Eastwood
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