engleski

Adaptive thermogenesis in brown adipose tissue is affected by constitutive serotonergic tone: study on Wistar-Zagreb 5HT rat model

Introduction: A biogenic amine serotonin (5HT) acts in the brain as anorexigenic transmitter, but systemic up-regulation of 5HT is associated with increased adiposity, suggesting that central and peripheral 5HT affect energy status in an opposite manner. In addition to regulating energy metabolism in white adipose tissue, peripheral 5HT influences adaptive thermogenesis in brown adipose tissue (BAT), an organ with a large ability to convert chemical energy into heat. Due to BAT potential to stimulate energy expenditure, its activation has been suggested as anti-obesity treatment. Methods: To better understand the role of 5HT in adaptive BAT thermogenesis we use Wistar-Zagreb 5HT rats, an animal model consisting of two sublines with constitutionally altered 5HT homeostasis (high-5HT and low-5HT subline), developed by selective breeding toward extreme activities of peripheral (platelet) 5HT transporter. Rats from the high-5HT subline have increased body weight and moderate obesity phenotype accompanied with lower BAT weight and lower skin temperature above BAT in comparison with low-5HT animals. Here we compared BAT thermogenesis in groups of rats from two 5HT-sublines which were either kept under usual temperature conditions (22ºC) or intermittently subjected to cold environment for five weeks (8ºC, 4 hours/day, 5 days/week). During this period we have periodically measured their food intake, body temperature (by rectal probe) and temperature above the intrascapular BAT (by infrared thermography). At the end of experiment, we determined BAT mass and evaluated BAT protein (by ELISA) and mRNA (by RT-qPCR) levels of the key protein in dissipating energy into heat (uncoupled protein-1, UCP1). In addition, mRNA levels of several transcription factors involved in BAT adipogenesis were measured. Results: Results show that rats from the high- 5HT subline (i.e. hyperserotonergic animals) have higher increase in food intake, BAT weight and skin temperature above BAT in response to low ambient temperature as compared to rats from the low-5HT subline. High-5HT rats also showed higher increase in UCP1 expression at both, protein and mRNA levels. No differences in response to cold-activation of BAT between 5HT- sublines were shown with regard to expression levels of Ppara, while alterations in Cebpb mRNA (decrease) and Pparg1a mRNA (increase) levels were present only in the low-5HT animals. Conclusion: Our findings obtained in an original rodent model demonstrated that individual differences in serotonergic tone affect the adaptive response of BAT to low ambient temperature. They also validate Wistar-Zagreb 5HT rats as a potential novel genetic model in obesity research. Funding: Research was funded by Croatian Science Foundation, grant no IP-2014-09-7827

Serotonin ; brown adipose tissue ; thermogenesis

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