Sexual Dimorphism in Clock Genes Expression in Human Adipose Tissue

Abstract

Background 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/m2), 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. Results Gene expression was significantly higher in women than in men for the three genes studied in both ATs (P<0.05). In visceral fat, these differences were more marked. (P<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<0.05). Moreover, we found significant associations with body fat mass in women and with age in men. Conclusions 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.

Sex differences in adipose tissue

“…Many of these genes code for proteins involved in immune response as well as lipid, protein, or carbohydrate metabolism. The expression of clock genes (PER2, BMAL1, and CRY1) are also higher in subcutaneous and visceral fat from obese females compared with males, with the differences being greatest in visceral fat 37 . As discussed below, dissimilarities in circulating levels of gonadal steroids may underlie some of these sex differences, but others appear to be independent of gonadal hormones.…”

Systems analysis of sex differences reveals an immunosuppressive role for testosterone in the response to influenza vaccination

“…The regulatory program derived for module 106 ( Fig. S1) included genes previously shown to be differentially regulated in males versus females, such as CLOCK (18), ENY2 (19), and IRF1 and IRF7 (20).…”

Autophagy in Adipose Tissue

“…An additional interesting possibility arises from the demonstration that expression of autophagy genes exhibits a strong diurnal rhythm and may be regulated by biological clock genes [33,34]. Given the increasingly appreciated role of disrupted biological clocks in metabolic diseases [35,36] and early reports that clock genes may be altered in AT in obesity [37,38], it is tempting to propose disturbed clock gene regulation as a putative cause of, or at least a significant contributor to, altered autophagy in AT. In addition, in many obese individuals AT becomes insulin-resistant.…”