engleski

Relationship between thermoregulation, obesity and serotonergic homeostasis: a study in Wistar-Zagreb 5HT rat model

The global epidemic of obesity forced the question of the fundamental causes of excessive weight gain. The observation that maintenance of core body temperature accounts for a substantial proportion of energy expenditure raises the possibility that lower core body temperature (i.e. decreased energy expenditure requirements) might predispose individuals to obesity . Some inherited forms of rodent obesity (e.g. leptin deficient ob/ob mouse, Zucker fatty fa/fa rat) are hypothermic compared with lean control and withstand cold poorly. Obese humans, however, have normal core temperatures. Brain serotonergic (5HT) pathways are involved in many physiological functions including both thermoregulation/thermogenic response and energy intake/energy consumption. In serotonin- deficient mice (TPH2 knockout) basic body temperature was normal, but thermogenic response to cold was more pronounced. Data on the relation between 5HT availability and body weight in both humans and animal models are mixed. To better understand the integrative role of 5HT signaling in mammalian (patho)physiology we use Wistar- Zagreb 5HT rats, animal model developed by selective breeding of rats toward the activity of peripheral 5HT transporter (5HTT), consisting of two sublines with genetically altered central and peripheral 5HT homeostasis. Rats from the high-5HT subline (i.e. hyperserotonergic rats) were shown to have obesity phenotype. This work addresses the interrelation of body temperature and obese state in association with constitutionally altered 5HT system. Additional consideration is given to hypothermic and hyperthermic reaction of 5HT-sublines to various conditions including pharmacological manipulations and environmental challenges. We observed that core body temperature did not differ significantly between high-5HT and low- 5HT animals at rest, while the observed increase or decrease in body temperature in response to various challenges was subline and gender dependent. Taken together, results suggest that interrelation between thermal and energy balance may differ in individuals with constitutional (inherited) or provoked (eg. by pharmacological treatment) alterations of serotonin system activity.

thermoregulation; obesity; serotonin; Wistar-Zagreb 5HT rats

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