Abstract
BackgroundZucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is now thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance.MethodsIn this study we investigated the effects of obesity and hyperinsulinemia on ovarian morphology and the hormone profile in insulin-resistant Zucker fatty rats (5, 8, 12 and 16 weeks of age, n = 6-7).ResultsOvaries from 5-week-old fatty rats had significantly greater total and atretic follicle numbers, and higher atretic-to-total follicle ratios than those from lean rats. Ovaries from 12- and 16-week-old fatty rats showed interstitial cell hyperplasia and numerous cysts with features of advanced follicular atresia. In addition, serum testosterone and androstenedione levels significantly declined in fatty rats from age 8 to 16 weeks, so that fatty rats showed significantly lower levels of serum testosterone (12 and 16 weeks) and androstenedione (all weeks) than lean rats. This may reflect a reduction of androgen synthesis during follicular atresia. Serum adiponectin levels were high in immature fatty rats, and although the levels declined significantly as they matured, it remained significantly higher in fatty rats than in lean rats. On the other hand, levels of ovarian adiponectin and its receptors were significantly lower in mature fatty rats than in lean mature rats or immature fatty rats.ConclusionsOur findings indicate that ovarian morphology and hormone profiles are significantly altered by the continuous insulin resistance in Zucker fatty rats. Simultaneously, abrupt reductions in serum and ovarian adiponectin also likely contribute to the infertility seen in fatty rats.
Highlights
Zucker fatty rats are a well-understood model of obesity and hyperinsulinemia
Hormone profile in Zucker fa/fay and lean rats Hormone assays were carried using serum samples collected from rats at 5, 8, 12 and 16 weeks of age, during diestrous, after they were fasted for 12 h (n = 6 or 7 in each group)
Serum testosterone increased significantly as they matured during the period from age 5 to 8 weeks, after which the levels remained stable until the rats were 16 weeks of age
Summary
Zucker fatty (fa/fa) rats are a well-understood model of obesity and hyperinsulinemia. It is thought that obesity/hyperinsulinemia is an important cause of endocrinological abnormality, but to date there have been no reports on the changes in ovarian morphology or the ovarian androgen profile in rat models of obesity and insulin resistance. Zucker fatty rats have several endocrine and metabolic abnormalities, including a low metabolic rate [2], hyperinsulinemia [3,4], abnormal estrous cyclicity [5] and infertility [3]. Adiponectin is a 30-kDa protein comprised of 247 amino acids in four domains and has been shown to possess insulin-sensitizing [6,7,8], anti-atherogenic [9,10] and anti-inflammatory properties [11]. Our aim in the present study, was to investigate the ovarian morphology and hormone profile in Zucker fatty rats, focusing on serum androgen levels and ovarian adiponectin expression
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