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Publication : Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior.

First Author  Costello HM Year  2023
Journal  Function (Oxf) Volume  4
Issue  2 Pages  zqad001
PubMed ID  36778748 Mgi Jnum  J:338410
Mgi Id  MGI:7512707 Doi  10.1093/function/zqad001
Citation  Costello HM, et al. (2023) Adrenal-Specific KO of the Circadian Clock Protein BMAL1 Alters Blood Pressure Rhythm and Timing of Eating Behavior. Function (Oxf) 4(2):zqad001
abstractText  Brain and muscle ARNT-like 1 (BMAL1) is a core circadian clock protein and transcription factor that regulates many physiological functions, including blood pressure (BP). Male global Bmal1 knockout (KO) mice exhibit approximately 10 mmHg reduction in BP, as well as a blunting of BP rhythm. The mechanisms of how BMAL1 regulates BP remains unclear. The adrenal gland synthesizes hormones, including glucocorticoids and mineralocorticoids, that influence BP rhythm. To determine the role of adrenal BMAL1 on BP regulation, adrenal-specific Bmal1 (AS(Cre/+) ::Bmal1) KO mice were generated using aldosterone synthase Cre recombinase to KO Bmal1 in the adrenal gland zona glomerulosa. We confirmed the localization and efficacy of the KO of BMAL1 to the zona glomerulosa. Male AS(Cre/+) ::Bmal1 KO mice displayed a shortened BP and activity period/circadian cycle (typically 24 h) by approximately 1 h and delayed peak of BP and activity by approximately 2 and 3 h, respectively, compared with littermate Cre- control mice. This difference was only evident when KO mice were in metabolic cages, which acted as a stressor, as serum corticosterone was increased in metabolic cages compared with home cages. AS (Cre/+) ::Bmal1 KO mice also displayed altered diurnal variation in serum corticosterone. Furthermore, these mice have altered eating behaviors where they have a blunted night/day ratio of food intake, but no change in overall food consumed compared with controls. Overall, these data suggest that adrenal BMAL1 has a role in the regulation of BP rhythm and eating behaviors.
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