Central insulin sensitivity in male and female juvenile rats

Abstract

The incidence of juvenile obesity is increasing at an alarming rate. In adults, central insulin administration decreases hypothalamic orexigenic neuropeptides, food intake and body weight more effectively in males than females. Mechanisms regulating energy balance in juvenile animals are inherently different from those in adults due to differences in growth rates and hormonal milieu. Therefore, we sought to determine if central insulin treatment in juvenile rats (4 wk) would have similar sex-dependent effects on food intake as those reported in adult rats. Twenty four hour food intake was measured following icv saline or insulin (0.01 or 0.1 U) prior to the onset of dark phase of the light cycle. An additional set of animals was used to assess the effects of central insulin on hypothalamic orexigenic (NPY, AgRP) and anorexigenic (POMC) neuropeptide mRNA expression. In both males and females, insulin reduced meal size initially (first 4h) and later decreased meal frequency (4-24 h) to reduce cumulative food intake. Consistent with this, central insulin decreased hypothalamic NPY and AgRP and increased POMC mRNA expression. In contrast to adult studies, there were no demonstrated sex differences. These studies indicate that juvenile females and males are equally sensitive to central insulin anorexigenic effects, perhaps due to a lack of circulating gonadal hormones. The anorexigenic responsiveness of both genders suggests a potential pharmacologic approach to childhood obesity.

Fetal undernutrition is associated with perinatal sex-dependent alterations in oxidative status

“…For this reason we chose to study oxidative balance at the age of weaning. Furthermore, our data indicates that at this age, the rats are still in the prepuberal stage, as evidenced by the low levels of estrogens in both males and females, similar to previous reports [35]. This enabled us to assess if sex differences in oxidative status take place before sexual maturity.…”

Sex and Gender Differences in Risk, Pathophysiology and Complications of Type 2 Diabetes Mellitus

“…This is in agreement with findings in juvenile male and female rats with low levels of gonadal hormones. These featured similar anorexigenic effects of intranasal insulin with decrease in meal frequency and total food intake together with comparable changes in hypothalamic gene expression ( 262 , 264 ). These anorexigenic central nervous insulin effects shall be interesting for potential therapeutic approaches to treat childhood obesity in both sexes.…”

Ovarian hormones and obesity

“…Central administration of insulin was found to inhibit eating more in ovariectomized than in intact rats, and this was reversed by central estradiol administration (Clegg et al, 2006). These effects do not occur in peripubertal rats (Keen-Rhinehart et al, 2009), further suggesting an activational role of estradiol. Interestingly, female, but not male, transgenic mice with brain-specific null mutations of the insulin receptor are hyperphagic, which in females was related to profound reductions of LH and signs of defective ovarian follicle maturation, indicating a role for neural insulin receptors in the normal function of the hypothalamic-pituitary-gonadal axis (Brüning et al, 2000).…”