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

Autor: Costello HM; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.; Center for Integrative Cardiovascular and Metabolic Diseases, University of Florida, Gainesville, FL 32610, USA., Crislip GR; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.; Center for Integrative Cardiovascular and Metabolic Diseases, University of Florida, Gainesville, FL 32610, USA., Cheng KY; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA., Lynch IJ; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.; Research, North Florida/South Georgia Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL 32608, USA., Juffre A; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA., Bratanatawira P; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA., Mckee A; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA., Thelwell RS; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA., Mendez VM; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA., Wingo CS; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.; Research, North Florida/South Georgia Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL 32608, USA., Douma LG; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.; Center for Integrative Cardiovascular and Metabolic Diseases, University of Florida, Gainesville, FL 32610, USA., Gumz ML; Department of Physiology and Aging, University of Florida, Gainesville, FL 32610, USA.; Department of Medicine, Division of Nephrology, Hypertension, and Renal Transplantation, University of Florida, Gainesville, FL 32610, USA.; Center for Integrative Cardiovascular and Metabolic Diseases, University of Florida, Gainesville, FL 32610, USA.; Research, North Florida/South Georgia Malcolm Randall Veterans Affairs Medical Center, Gainesville, FL 32608, USA.; Department of Biochemistry and Molecular Biology, University of Florida, Gainesville, FL 32610, USA.
Jazyk: angličtina
Zdroj: Function (Oxford, England) [Function (Oxf)] 2023 Jan 09; Vol. 4 (2), pp. zqad001. Date of Electronic Publication: 2023 Jan 09 (Print Publication: 2023).
DOI: 10.1093/function/zqad001
Abstrakt: 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 ∼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 ∼1 h and delayed peak of BP and activity by ∼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. A S 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.
(© The Author(s) 2023. Published by Oxford University Press on behalf of American Physiological Society.)
Databáze: MEDLINE
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