Obesity Alters the Peripheral Circadian Clock in the Aorta and Microcirculation

Nitirut Nernpermpisooth, Shuiqing Qiu, James D. Mintz, Wisuda Suvitayavat, Suwan Thirawarapan, Radu Daniel Rudic, David J Fulton, David W Stepp

Research output: Contribution to journalArticle

9 Scopus citations

Abstract

Objective: Perturbation of daily rhythm increases cardiovascular risk. The aim of this study was to determine whether obesity alters circadian gene expression and microvascular function in lean mice and obese (db/db) mice. Methods: Mice were subjected to normal LD or DD to alter circadian rhythm. Metabolic parameters and microvascular vasoreactivity were evaluated. Array studies were conducted in the am and pm cycles to assess the rhythmicity of the entire genomics. Rhythmic expression of specific clock genes (Bmal1, Clock, Npas2, Per1, Per2, and Cry1), clock output genes (dbp), and vascular relaxation-related genes (eNOS, GTPCH1) were assessed. Results: Obesity was associated with metabolic dysfunction and impaired endothelial dilation in the microvasculature. Circadian rhythm of gene expression was suppressed 80% in both macro- and microcirculations of obese mice. Circadian disruption with DD increased fasting serum glucose and HbA1c in obese but not lean mice. Endothelium-dependent dilation was attenuated in obese mice and in lean mice subjected to DD. Rhythmic expression of per1 and dbp was depressed in obesity. Expression of eNOS expression was suppressed and GTPCH1 lost rhythmic expression both in obesity and by constant darkness. Conclusion: These results suggest that obesity reduces circadian gene expression in concert with impaired endothelial function. The causal relationship remains to be determined.

Original languageEnglish (US)
Pages (from-to)257-266
Number of pages10
JournalMicrocirculation
Volume22
Issue number4
DOIs
StatePublished - Jan 1 2015

Keywords

  • Circadian disruption
  • Clock genes
  • Obesity
  • Vascular function
  • eNOS

ASJC Scopus subject areas

  • Physiology
  • Molecular Biology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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