engleski

Obesity phenotype of rats with constitutional hyperactivity of serotonin transporter

An inverse relationship between brain serotonin (5-hydroxytryptamine, 5HT) system and food intake has been known for over 30 years. Specifically, increase of brain 5HT activity leads to decreased food intake and weight gain, and vice versa. The 5-HT transporter (5HTT) is an important regulator of brain 5HT function as it is responsible for reuptake of 5HT in serotonergic nerve endings. Studies have shown that inhibition of 5HTT reduces food intake and body weight gain in rats and humans, but much remains to be learned about the 5HT mechanisms underlying the regulation of obesity phenotype. In our research we use Wistar-Zagreb 5HT (WZ- 5HT) rats, an animal model with constitutively high or low 5HTT activity (termed high-5HT and low-5HT subline), developed in our laboratory by selective breeding of animals toward extremes of peripheral 5HTT activity. Besides in periphery, two sublines of WZ-5HT rats differ also in the central 5HT homeostasis, as evidenced from neurochemical and behavioral studies. Here, we aimed to compare phenotypes of animals from 5HT-sublines regarding their body weight, adiposity and fat distribution, as well as their food intake. Body weight (BW) accumulation was monitored from birth to senescence and body mass index (BMI, ratio of body weight and body lenght2), total body fat mass and pattern of adiposity were determined at 3 and 8 months of age. Animals from 5HT- sublines show clear differences in obesity phenotypes. Specifically, rats from the high- 5HT subline have shown a higher body weight in comparison to their low-5HT counterpart, and this difference is present throughout the entire period of observation. Body mass index was also higher in the high-5HT animals. Deposition of fat in several adipose tissue depots (visceral, retroperitoneal, gonadal and subcutaneous) in rats from 5HT sublines showed that the relative amount of fat pads (g of fat pad/100 g of BW) was significantly higher in rats from the high-5HT subline. The present data demonstrate that rats from the high-5HT subline of WZ-5HT model show clear obesity phenotype as compared to rats from the low-5HT subline. Results point to the fundamental role of individual variability in endogenous serotonergic tone in the control of body weight regulation. They also validate Wistar-Zagreb 5HT rats, with constitutionally upregulated/downregulated serotonin transporter, as a potential novel genetic model in obesity research.

serotonin ; obesity ; Wistar-Zagreb 5HT rats

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