Leek58pond: Створена сторінка: Whole body Disruption of circadian clock function influences metabolic homeostasis at multiple levels. At the whole-body level, both markers of acute (eg, nutri...

2017-03-11T15:27:43Z

Створена сторінка: Whole body Disruption of circadian clock function influences metabolic homeostasis at multiple levels. At the whole-body level, both markers of acute (eg, nutri...

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Whole body Disruption of circadian clock function influences metabolic homeostasis at multiple levels. At the whole-body level, both markers of acute (eg, nutrient clearance) and chronic (eg, body weight), metabolic perturbations have been interrogated. Initial SCN-ablation studies (a strategy that impairs not only central but also peripheral clock function) reported altered body weight in various rodent models.114�C116 This intervention also results in profound alterations in glucose homeostasis, affecting both insulin-dependent and independent glucose disposal.16 Animal models of genetic manipulation of circadian clock components have also been investigated. Of these, germline CLOCK?19 [http://www.selleckchem.com/products/nu7441.html click here] mutant (loss of Exon 19 of the CLOCK gene, resulting in a dominant negative mutant) and BMAL1 null mice have been investigated to the largest extent (due to marked impact on circadian clock function); it is noteworthy that metabolic parameters have been investigated in other genetic models (eg, knockout [KO]/mutation of various PER and CRY isoforms), albeit to a lesser extent. In terms of body weight regulation, CLOCK?19 mutant mice present with increased adiposity (on the B6 background), while BMAL1 null mice are more susceptible to high-fat-diet-induced adiposity (at a young age).117,118 Both CLOCK?19 mutant and BMAL1 null mice exhibit decreased glucose tolerance, as indicated by an elevated amount of glucose in the circulation following an acute ([http://www.selleckchem.com/products/BKM-120.html BKM120] Conversely, lipid tolerance is increased in CLOCK?19 mutant (ie, decreased triglyceride in circulation following an acute lipid load).120 Collectively, these data suggest that disruption of circadian clocks alters both long- (eg, adiposity) and short-term (eg, glucose/lipid [http://en.wikipedia.org/wiki/Oxygenase Oxygenase] tolerance) metabolic homeostasis. In contrast, an extensive literature search was unable to identify information regarding the impact of circadian clock disruption on protein/amino acid tolerance. Consistent with the first law of thermodynamics, alterations in adiposity/body weight suggest an imbalance between caloric intake and energy expenditure. This could arise through perturbations in food intake, digestion, and/or absorption following circadian clock disruption, as well as the balance between catabolic and anabolic pathways involved in nutrient/energy homeostasis. Evidence exists suggesting clock control of all these parameters. For example, CLOCK?19 mutant and BMAL1 null mice exhibit abnormalities in day�Cnight patterns of food intake, such that a more even distribution of caloric intake is observed over the 24-hour day (as opposed to typical food intake predominance during the active/dark phase).

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Leek58pond: Створена сторінка: Whole body Disruption of circadian clock function influences metabolic homeostasis at multiple levels. At the whole-body level, both markers of acute (eg, nutri...