Research Article: Ramadan fasting in Saudi Arabia is associated with altered expression of CLOCK, DUSP and IL-1alpha genes, as well as changes in cardiometabolic risk factors

Date Published: April 6, 2017

Publisher: Public Library of Science

Author(s): Ghada M. A. Ajabnoor, Suhad Bahijri, Noor Ahmad Shaik, Anwar Borai, Aliaa A. Alamoudi, Jumana Y. Al-Aama, George P. Chrousos, Henrik Oster.


During the fasting month of Ramadan, practicing Saudis develop severe disturbances in sleeping and feeding patterns. Concomitantly, cortisol circadian rhythm is abolished, diurnal cortisol levels are elevated and circulating levels of several adipokines are altered favouring insulin resistance.

To examine changes in the expression of CLOCK and glucocorticoid-controlled genes, such as DUSP1 and IL-1α in Saudi adults before and during Ramadan, and to investigate possible associations with selected cardiometabolic risk factors.

Healthy young volunteers (5 females, 18 males; mean age +SEM = 23.2 +1.2 years) were evaluated before Ramadan and two weeks into it. Blood samples were collected at 9 am (±1 hour) and twelve hours later for determination of serum lipid profile, high sensitivity CRP (hsCRP), and adiponectin. The expression of CLOCK, DUSP1 and IL-1α was evaluated in circulating leukocytes.

Mean levels of GGT and morning adiponectin decreased, while those of LDL-c/ HDL-c and atherogenic index (AI) increased significantly in Ramadan compared to Shabaan. There was no significant difference between morning and evening adiponectin during Ramadan, while the diurnal rhythm of hsCRP was lost. CLOCK gene expression mean was significantly higher in morning than in evening during Shabaan. Mean morning and evening DUSP1 mRNA levels showed significant increase during Ramadan compared to Shabaan, however, its diurnal rhythm was maintained. Morning IL-1α mRNA expression remained significantly higher than in the evening during Ramadan, but was markedly decreased compared to Shabaan.

Ramadan fasting in Saudi Arabia is associated with improvements in some cardiometabolic risk factors, such as circulating GGT and hsCRP and leukocyte expression of IL-1α mRNA, suggesting that intermittent fasting might have a beneficial component. These benefits may be offset by the previously reported dysregulation in the circadian rhythm, excess glucocorticoid levels and action, and insulin resistance, explaining increased prevalence of cardiometabolic disorders and type 2 diabetes mellitus.

Partial Text

Circadian rhythms control many physiologic processes, including energy metabolism, hormone biosynthesis, and immune responses. It is estimated that approximately 10% of the main transcriptome in mammalian cells is expressed with a circadian rhythm. Indeed, studies examining the physiologic effects of sleep restriction, reported changes in the circadian timing system [1], as well as immune [2] and endocrine [3, 4] variables.

Results of estimated and calculated biochemical parameters estimated at different points of the study are presented in Table 2 (S1 Dataset).

It is believed that shift work uncouples the biological circadian clock and the external world zeitgebers, which, in turn, may contribute to shift-work associated diseases [11–13].




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