title: Obesity alters the peripheral circadian clock in the aorta and microcirculation.
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.
  
  
  CONCLUSIONS
  These results suggest that obesity reduces circadian gene expression in concert with impaired endothelial function. The causal relationship remains to be determined.
authors: Department of Physiology, Faculty of Pharmacy, Mahidol University, Bangkok, Thailand.
authors: Nitirut
authors: N
authors: Nernpermpisooth
authors: Shuiqing
authors: S
authors: Qiu
authors: James D
authors: JD
authors: Mintz
authors: Wisuda
authors: W
authors: Suvitayavat
authors: Suwan
authors: S
authors: Thirawarapan
authors: Daniel R
authors: DR
authors: Rudic
authors: David J
authors: DJ
authors: Fulton
authors: David W
authors: DW
authors: Stepp
mesh_terms: D000818:Animals; D001011:Aorta / Q000378:metabolism / Q000503:physiopathology; D057906:Circadian Clocks; D005786:Gene Expression Regulation; D008297:Male; D051379:Mice; D008833:Microcirculation; D009765:Obesity / Q000378:metabolism / Q000503:physiopathology
keywords: circadian disruption; clock genes; eNOS; obesity; vascular function