Table 1.

Altered expression profiles of molecular components of the circadian timing system in subjects with metabolic dysfunction that are directly or indirectly associated with a disrupted dipping pattern of BP.

Experimental Model	Molecular Mechanism	Altered Physiological Functions	References
db/db mice (type 2 diabetic model)	Attenuated circadian oscillation of Bmal1 and Dbp	Hypertension, disrupted BP circadian rhythm	Su et al. 2008 [17]
db/db mice	Altered clock gene expression both in central (Per1) and peripheral clock (Per1/2, Cry1/2), as well as their target genes (Dbp, Pparγ, Rev-erbα)	Disrupted diurnal contraction of vasculature	Su et al. 2012 [18]
High-fat-diet-induced obesity in mice	Altered circadian oscillation of clock (Per1-3; Cry1/2; Bmal1) and clock-controlled (Dbp, E4bp4, Pdk4, Pepck, Nhe3) genes	Hyperglycemia, hypercholesterolemia, hyperinsulinemia	Hsieh et al. 2010 [19]
db/db mice	Altered rhythmic expression of Per2 and Bmal1, increased Pai-1 mRNA expression	Attenuated circadian behavior	Kudo et al. 2004 [20]
Streptozotocin (STZ)-induced diabetes in Clock-mutant mice	Circadian augmentation of Pai-1 is diminished	Clock is involved in the diabetes-induced circadian augmentation of Pai-1	Oishi et al. 2005 [21]
Dim light at night (alteration of circadian timing system) in mice	Attenuated circadian oscillation of Per1 and Per2 in hypothalamus, and Rev-Erb in liver and adipose tissue	Onset and progression of metabolic abnormalities	Fonken et al. 2011 [22]
Human subjects with type 2 diabetes (T2D)	BMAL1 single nucleotide polymorphisms (SNPs) (2 BMAL1 haplotypes)	SNP is associated with hypertension and T2D	Woon et al. 2007 [23]
Human subjects with T2D	CLOCK-rs4580704 (C > G) SNP	Cardiovascular (CV) disorders	Corella et al. 2016 [24]
Human subjects with rotating shiftwork	Interaction (epistatic effect) of serotonin transporter and CLOCK gene variation	Metabolic abnormalities	Sookoian et al. 2010 [25]
STZ-induced diabetes in mice	Altered circadian oscillation of core clock and their target genes	Contractile dysfunction of the heart	Young et al. 2002 [26]