Sexual Dimorphism and Regulation of Resistin, Adiponectin, and Leptin Expression in the Mouse

Abstract

GUI, YAOTING, JOSEF V. SILHA, AND LIAM J. MURPHY. Sexual dimorphism and regulation of resistin, adiponectin, and leptin expression in the mouse. Obes Res. 2004;12:1481-1491. Objective: To examine gender differences and hormonal regulation of resistin, adiponectin, and leptin. Research Methods and Procedures: Plasma levels were measured, and mRNA expression in perigonadal fat was quantified by RNase protection assays. Results: Plasma resistin declined with age despite an increase in adiposity in both genders. In male mice, plasma leptin increased, whereas adiponectin levels were constant. In females, both adiponectin and leptin levels increased with age. Resistin mRNA levels were significantly higher in female than male mice at all ages, whereas leptin and adiponectin mRNA levels were similar in fat from 6-weekold male and female mice, and sexual dimorphism was apparent only in the older mice, with higher levels apparent in females. Castration did not abolish gender differences in plasma levels or resistin, adiponectin, or leptin mRNAs. Castration of male mice did not significantly change adipokine mRNA levels or plasma levels of resistin or leptin; however, adiponectin was significantly increased. Dihydrotestosterone treatment had no effect on adipokine mRNA expression or resistin and adiponectin levels but increased leptin levels. In contrast, ovariectomy significantly increased resistin mRNA abundance and decreased leptin and adiponectin mRNAs. Plasma leptin levels were also increased by ovariectomy, whereas resistin and adiponectin levels were unchanged. Estrogen replacement significantly reduced resistin mRNA and increased leptin and adiponectin mRNA levels but had no effect on plasma adipokine levels. Discussion: The gender differences in adipokine mRNA expression and plasma levels were not ablated by castration and seem to be dependent on other factors in addition to gonadal steroids.

Normative data for adiponectin, resistin, interleukin 6, and leptin/receptor ratio in a healthy Spanish pediatric population: relationship with sex steroids

“…However, in agreement with most (38, 39), but not all (37) reports, we found no correlation of resistin with sex steroids or BMI. This lack of correlation is consistent with results from animal studies where estradiol did not modify plasma resistin levels (40). However, the fact that resistin levels are their highest in adult females and correlate with the leptin/receptor ratio, which does not occur in males, suggests a possible link between resistin levels and female body fat content changes.…”

Testosterone Selectively Reduces the High Molecular Weight Form of Adiponectin by Inhibiting Its Secretion from Adipocytes

“…Nevertheless, the mechanisms that underlie the regulatory effect of testosterone on adiponectin production are still poorly understood. Neither castration nor testosterone interferes with the mRNA abundance of the adiponectin gene in adipocytes (27,34), although these treatments modulate the serum levels of total adiponectin, suggesting that the regulation occurs at a posttranscriptional level. In this study we provide both experimental and clinical evidence demonstrating that testosterone exerts its regulatory actions at the level of adiponectin oligomeric complex distribution.…”

The effects of LPS-induced endotoxemia on the expression of adiponectin and its receptors in female rats

“…It has also been suggested that a certain degree of sexual dimorphism exists in the regulation of APN expression under non-stress conditions. For example, serum APN levels are increased by aging in female, but not male, mice [19]. In addition, the changes in cytokine production caused by LPS-induced sepsis have also been reported to exhibit sexual dimorphism [27].…”

“…Furthermore, the changes in hypothalamic AdipoR and subcutaneous APN mRNA levels induced under septic conditions also remain to be investigated. As it has been suggested that basal adiponectin levels exhibit a certain degree of sexual dimorphism [19], we speculate that the changes in the expression levels of adiponectin and its receptors induced in response to acute inflammatory conditions might also differ between the sexes. Accordingly, the present study evaluated the changes in APN and AdipoR expression at the peripheral and central levels; i.e., their serum, WAT, hepatic, and hypothalamic levels, under LPS-induced septic conditions in female rats.…”

“…Accordingly, the present study evaluated the changes in APN and AdipoR expression at the peripheral and central levels; i.e., their serum, WAT, hepatic, and hypothalamic levels, under LPS-induced septic conditions in female rats. Both gonadal-intact and ovariectomized (OVX) rats were used because it has been suggested that gonadal steroids might affect the serum APN levels of female rodents [19,20]. In addition, as APN has been reported to suppress the serum and hepatic concentrations of IL-6 and TNF-α, their defined as 1.0.…”