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United States Department of Agriculture

Agricultural Research Service

Research Project: NUTRITION, OBESITY, CARDIOVASCULAR HEALTH AND GENOMICS

Location: Human Nutrition Research Center on Aging

Title: Sexual dimorphism in clock genes expression in human adipose tissue

Authors
item Gomez-Abellan, Purificacion -
item Madrid, Juan -
item Lujan, Juan -
item Frutos, M -
item Gonzalez, Raquel -
item Martinez-Augustin, Olga -
item Sanchez DE Medina, Fermin -
item Ordovas, Jose -
item Gauralet, Marta -

Submitted to: Obesity Surgery
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: June 1, 2011
Publication Date: January 1, 2012
Citation: Gomez-Abellan, P., Madrid, J.A., Lujan, J.A., Frutos, M.D., Gonzalez, R., Martinez-Augustin, O., Sanchez De Medina, F., Ordovas, J.M., Gauralet, M. 2012. Sexual dimorphism in clock genes expression in human adipose tissue. Obesity Surgery. 22(1):105-112.

Interpretive Summary: A circadian rhythm is any biological process that displays an internally regulated, repetitive variation of time of about 24 hours. These rhythms are driven by a circadian clock, and there are many health problems (i.e., obesity, cardiovascular diseases, neurological disorders) associated with disturbances of the human circadian rhythm. These disturbances may be driven by environmental as well as by genetic factors. Regarding the effect on obesity, it is known that human body fat (adipose tissue - AT) shows circadian rhythmicity but an integrated study of the factors involved in its regulation has not been reported on. This study was carried out to investigate whether sex-related differences exist in the fat cell expression of clock genes from fat located beneath the skin (subcutaneous adipose tissue SAT) and fat surrounding the organs (visceral adipose tissue- VAT) in severely obese patients. We investigated 16 morbidly obese patients, eight men and eight women (mean age 45 years and a body mass index of 46 kg/m(2)), undergoing laparoscopic gastric bypass surgery. Biopsies were taken as paired samples (VAT+SAT) in these samples we measured the expression of clock genes (PER2, BMAL1, and CRY1) using quantitative real-time PCR, Western blot, and immunohistochemical analysis. Our data show that gene expression was significantly higher in women than in men for the three genes studied in both VAT and SAT, with the differences being more marked in visceral fat. Interestingly, clock gene expression level was correlated with low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C). Moreover, we found significant associations with body fat mass in women and with age in men. In summary, clock genes’ expression is sex dependent in human adipose tissue from morbidly obese subjects and correlates with decreased metabolic syndrome-related traits.

Technical Abstract: This study was carried out to investigate whether sex-related differences exist in the adipocyte expression of clock genes from subcutaneous abdominal and visceral fat depots in severely obese patients. METHODS: We investigated 16 morbidly obese patients, eight men and eight women (mean age 45 +/- 20 years; mean BMI 46 +/- 6 kg/m(2)), undergoing laparoscopic gastric bypass surgery. Biopsies were taken as paired samples [subcutaneous and visceral adipose tissue (AT)] at the beginning of the surgical process at 11:00 h in the morning. Metabolic syndrome features such as waist circumference, plasma glucose, triglycerides, total cholesterol, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) were also studied. The expression of clock genes (PER2, BMAL1, and CRY1) was measured by quantitative real-time PCR, Western blot, and immunohistochemical analysis. Gene expression was significantly higher in women than in men for the three genes studied in both ATs (P less than 0.05). In visceral fat, these differences were more marked. (P less than 0.001). Western blot analysis partially confirmed these results since statistical differences were observed for PER2 in both ATs and for CRY1 in subcutaneous adipose tissue. There were no differences in BMAL1 protein expression. Interestingly, clock gene expression level was correlated with LDL-C and HDL-C (P less than 0.05). Moreover, we found significant associations with body fat mass in women and with age in men. Clock genes expression is sex dependent in human adipose tissue from morbidly obese subjects and correlates to a decreased in metabolic syndrome-related traits. These preliminary results make necessary to go deep into the knowledge of the molecular basis of the sexual dimorphism in chronobiology.

Last Modified: 9/21/2014