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Version actuelle en date du 2 février 2017 à 14:29

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 buy NU7441 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 (selleck 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 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).