engleski

Differential expression of obesity-related genes in hypothalamus of Wistar-Zagreb 5HT rats

It is well known that brain serotonin (5- hydroxytryptamine, 5HT) signaling affects the body weight regulation by acting at multiple sites at the brainstem and hypothalamic level and by interacting with various orexigenic and anorexigenic networks. It is generally accepted that increased brain 5HT activity is associated with reduced food intake and body weight, but recent findings point to much greater complexity of 5HT mechanisms implicated in the regulation of energy balance. Animal model termed Wistar-Zagreb 5HT rats, consisting of two sublines with constitutionally altered serotonin homeostasis (high-5HT and low- 5HT subline), was developed in our laboratory by selective breeding of animals toward naturally occurring extreme activities of peripheral serotonin transporter, a key regulator of serotonergic transmission. Interestingly, animals from the high-5HT subline display lifelong elevated body weight and a clear adult obesity (higher body mass index, higher deposition of fats in adipose tissue depots, abdominal adiposity) in comparison to the low-5HT animals. These sublines hence represent an interesting model for investigating a role of constitutive differences in serotonin signaling in the modulation of body weight. In search for molecular pathways implicated in the body weight regulation, here we aimed to identify genes that might be differentially expressed in hypothalami of animals from high-5HT and low-5HT sublines. By the use of real-time PCR arrays (Rat Obesity RT2 Profiler PCR Array and Rat Adipogenesis RT2 Profiler PCR Array, Qiagene) we have investigated expression levels of over 160 genes known to be implicated in the regulation of adipogenesis, energy expenditure and orexigenic and anorectic pathways. Expression levels of genes of interest were normalized to geometric mean of six housekeeping genes and fold changes between 5HT- sublines were calculated. We have identified 3 genes possibly over-expressed in the hypothalamus of high-5HT animals, while 28 genes appeared to be down-regulated in this subline, in comparison to animals from the low-5HT subline. Results obtained by gene expression profiling will be further confirmed using quantitative real-time PCR as well as ELISA measurements.

obesity; serotonin; Wistar-Zagreb 5HT rats

nije evidentirano