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Article Dans Une Revue Biochimie Année : 2016

Circadian phenotyping of obese and diabetic db/db mice

Résumé

Growing evidence links metabolic disorders to circadian alterations. Genetically obese db/db mice, lacking the long isoform of leptin receptor, are a recognized model of type 2 diabetes. In this study, we aimed at characterizing the potential circadian alterations of db/db mice in comparison to db/þ control mice. By using telemetry devices, we first reported arrhythmicity in general activity of most db/db mice under both lightedark cycle and constant darkness, while their rhythm of body temperature is less dramatically disrupted. Water access restricted to nighttime restores significant rhythmicity in behaviorally arrhythmic db/db mice, indicating a masking effect of polydipsia when water is available ad libitum. Endogenous period of temperature rhythm under constant dark conditions is significantly increased (þ30 min) in db/db compared with db/þ mice. Next, we studied the oscillations of clock proteins (PER1, PER2 and BMAL1) in the suprachiasmatic nuclei (SCN), the site of the master clock, and detected no difference according to the genotype. Furthermore, c-FOS and P-ERK1/2 expression in response to a light pulse in late night was significantly increased (þ80 and þ55%, respectively) in the SCN of these diabetic mice. We previously showed that, in addition to altered activity rhythms, db/db mice exhibit altered feeding rhythm. Therefore, we investigated daily patterns of clock protein expression in medial hypothalamic oscillators involved in feeding behavior (arcuate nucleus, ventro- and dorso-medial hypothalamic nuclei). Compared with db/þ mice, very subtle or no difference in oscillations of PER1 and BMAL1 is found in the medial hypothalamus. Although we did not find a clear link between altered hypothalamic clockwork and behavioral rhythms in db/db mice, our results highlight a lengthened endogenous period and altered photic integration in these genetically obese and diabetic mice

Dates et versions

hal-01298505 , version 1 (06-04-2016)

Identifiants

Citer

Edith Grosbellet, Stephanie Dumont, Carole Schuster-Klein, Beatrice Guardiola-Lemaitre, Paul Pevet, et al.. Circadian phenotyping of obese and diabetic db/db mice. Biochimie, 2016, 124, pp.198-206. ⟨10.1016/j.biochi.2015.06.029⟩. ⟨hal-01298505⟩
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