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United States Department of Agriculture

Agricultural Research Service

Research Project: NUTRITION, OBESITY, CARDIOVASCULAR HEALTH AND GENOMICS Title: Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women

Authors
item Hernandez-Morante, Juan -
item Gomez-Santos, Cecilia -
item Margareto, Javier -
item Formiguera, Xavier -
item Martinez-Carlos, Manuel -
item Gonzalez, Raquel -
item Martinez-Augustin, Olga -
item Madrid, Juan -
item Ordovas, Jose -
item Garaulet, Marta -

Submitted to: Age
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: August 24, 2011
Publication Date: September 7, 2011
Citation: Hernandez-Morante, J.J., Gomez-Santos, C., Margareto, J., Formiguera, X., Martinez-Carlos, M., Gonzalez, R., Martinez-Augustin, O., Madrid, J.A., Ordovas, J.M., Garaulet, M. 2011. Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women. Age. DOI 10.1007/s11357-011-9309-2.

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 disease, neurological disorders) associated with disturbances of the human circadian rhythm. These disturbances may be driven by environmental as well as by genetic factors. Specifically, menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of body fat. However, the genetic contribution to these alterations has not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in body fat, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS). For this purpose, biopsies were taken from both the fat surrounding the organs (visceral adipose tissue- VAT) and fat located beneath the skin (subcutaneous adipose tissue SAT) in pre- (n'='7) and postmenopausal (n'='7) women at similar hours in the morning. Gene expression was measured in these samples. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the clock gene PERIOD3 was significantly higher in postmenopausal women, while casein kinase-1 Delta, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, PERIOD2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. In addition, several genes were differentially expressed depending on whether or not the subject met the MetS criteria. Our data indicate that menopause induces changes in the expression of the adipose tissue chronobiological machinery that may be relevant to the increased risk of developing MetS observed in postmenopausal women.

Technical Abstract: Menopausal women exhibit a loss of circadian coordination, a process that runs parallel with a redistribution of adipose tissue. However, the specific genetic mechanisms underlying these alterations have not been studied. Thus, the aim of the present study was to determine whether the development of menopause induces an alteration of the genes that control biological rhythms in human subcutaneous (SAT) and visceral (VAT) adipose tissue, and whether changes in clock gene expression are involved in the increased risk of developing metabolic syndrome (MetS), which is frequently associated with menopause. To this end, VAT and SAT biopsies were taken in pre- (n'='7) and postmenopausal (n'='7) women at similar hours in the morning. RNA was extracted, and a microarray analysis was made. Data were confirmed by quantitative real-time polymerase chain reaction. Western blot and immunohistochemical analysis were also performed. When clock gene expression was compared between both groups of women, data in SAT showed that expression of the core clock gene period3 was significantly higher in postmenopausal women, while casein kinase-1 Delta, E1A-binding protein and cAMP-responsive element were preferentially expressed in the premenopausal group. In VAT, period2 (PER2) and v-myc myelocytomatosis viral oncogene expressions were significantly higher in the postmenopausal group. Western blot analysis indicated that PER2 and PER3 protein expression was also increased in postmenopausal women. In addition, several genes, including PER2, were differentially expressed depending on whether or not the patient met the MetS criteria. We conclude that menopause transition induces several changes in the genotype of the adipose tissue chronobiological machinery related to an increased risk of developing MetS.

Last Modified: 10/21/2014
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