Body mass index and clock gene expression in human dermal fibroblasts

Introduction:

Circadian clocks are involved in the control of energy balance and regulation of body weight. The goal of this post-hoc analysis was to determine if higher body mass index (BMI) is associated with circadian gene oscillation using human dermal fibroblasts (HDF) as an ex vivo in vitro model.

Methods:

Eleven normal weight (NW; 5 men and 6 women; 36.73 ± 12.45 years, mean ± SD; BMI: 22.14 ± 2.04 kg/m2, mean ± SD) and thirteen overweight (OW) participants (7 men and 6 women; 39.00 ± 11.37 years, mean ± SD; BMI: 28.29 ± 3.44 kg/m2, mean ± SD) were included in the analysis. BMI value of 24.9 was used as cut off value. All study participants completed the Multiple-Choice Word test (IQ score NW = 117.36 ± 13.49, mean ± SD; OW = 115.23 ± 12.54, mean ± SD, n.s) and German Morningness-Eveningness-Questionnaire (D-MEQ Score: NW = 54.36 ± 14.71, mean ± SD; OW = 56.92 ± 8.71, mean ± SD, n.s). HDF were obtained via skin biopsy and cultured (37 °C, 5% CO2). After dexamethasone synchronization, samples were collected every four hours for a period of 24 hours. The expression of CLOCK, BMAL1, CRY1, PER1/2/3 was measured using qRT-PCR and data was controlled for fitting in a time series model (CircWave). Statistics were calculated using SPSS.

Results:

BMI values between NW and OW differed significantly (P < 0.001, Student's t-test). Study participants exhibited neutral chronotype (36.4% NW and 61.5% OW) and moderate morning type (27.3% NW and 30.8% OW). BMAL1 rhythmicity as well as CRY1 and PER1/2/3 was observed in both groups. Interestingly, NW did not present CLOCK rhythmicity (P > 0.05, CircWave); however, the OW group did (P < 0.0001, CircWave).

Conclusion:

Our pilot data suggests that BMI might influence CLOCK gene expression.