Activation of hypothalamic NPY, AgRP, MC4R, and IL-6 mRNA levels in young Lewis rats with early-life diet-induced obesity
Abstract
Obesity represents a low-grade inflammatory disease and is a risk factor for insulin resistance. Little is known whether this state may contribute to the development of autoimmune inflammatory diseases.
The aim of this work was to study the early-life diet-induced obesity in Lewis rats which are known by high susceptibility to autoimmunity. METHODS: Obesity was induced by small litter size (4 pups per litter) followed by high-fat diet (SHF rats).
Control rats (8 pups per litter) were fed with standard diet (CN rats). RESULTS: During the study SHF rats had the same body weight gain and caloric intake as CN rats.
At the age of 8 weeks SHF showed increased epididymal fat mass and adipocyte volume, impaired glucose tolerance, normal basal fasting insulin, visfatin, and ghrelin levels, lowered adiponectin, and high leptin levels. In the hypothalamic arcuate nucleus, SHF showed increased expressions of the orexigenic neuropeptide-Y (NPY), agouti-related protein (AgRP), and the anorexigenic pro-inflammatory cytokine IL-6 mRNAs.
In the paraventricular nucleus, SHF showed increased mRNA expressions for anorexigenic melanocortin 4 receptor (MC4R) and IL-6. CONCLUSIONS: Overexpression of the orexigenic hypothalamic NPY and AgRP indicates leptin resistance in SHF rats.
The increased expression of MC4R in PVN points to the activation of melanocortin anorexigenic system which along with increased hypothalamic IL-6 might prevent the animals from overfeeding. Higher adiposity in these rats results from the high fat-diet composition and not from increased caloric intake.
Furthermore, enhanced leptin production is the main factor indicating the predisposition to autoimmunity in these overfed rats.