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-1δ, 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.
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Supplementary table 1
Subcutaneous adipose tissue relative mRNA expression (arbitrary units) of all the clock-related genes analyzed in the present study. (DOCX 19 kb)
Supplementary table 2
Visceral adipose tissue relative mRNA expression (arbitrary units) of all the clock-related genes analyzed in the present study. (DOCX 19 kb)
Supplementary table 3
Variations in visceral and subcutaneous adipose tissue expression level of the different genes selected for microarray data validation (by mean of the real-time quantitative PCR method) between pre- and postmenopausal women. (DOCX 19 kb)
Supplementary Figure 1
Images derived from the inmunocytochemical analysis (x200) for both adipose tissue depots (subcutaneous and visceral) and both menopausal status (PRE and POST-menopausal women) to detect the presence of T-lymphocytes (stained with anti-CD3 antibodies). An image derived from sections of frozen human thymus (positive control)(x200) is included. (JPEG 1338 kb)
Supplementary Figure 2
Images derived from the inmunocytochemical analysis (x200) for both adipose tissue depots (subcutaneous and visceral) and both menopausal status (PRE and POST-menopausal women) to detect the presence of macrophages (stained with anti-CD14 antibodies). The arrows indicate the existence of a macrophage. (JPEG 982 kb)
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Hernandez-Morante, J.J., Gomez-Santos, C., Margareto, J. et al. Influence of menopause on adipose tissue clock gene genotype and its relationship with metabolic syndrome in morbidly obese women. AGE 34, 1369–1380 (2012). https://doi.org/10.1007/s11357-011-9309-2
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DOI: https://doi.org/10.1007/s11357-011-9309-2