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Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis


Kesić, Maja; Baković, Petra; Horvatiček, Marina; Proust, Bastien Lucien Jean; Štefulj, Jasminka; Čičin-Šain, Lipa
Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis // Frontiers in neuroscience, 14 (2020), 219, 14 doi:10.3389/fnins.2020.00219 (međunarodna recenzija, članak, znanstveni)


Naslov
Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis

Autori
Kesić, Maja ; Baković, Petra ; Horvatiček, Marina ; Proust, Bastien Lucien Jean ; Štefulj, Jasminka ; Čičin-Šain, Lipa

Izvornik
Frontiers in neuroscience (1662-453X) 14 (2020); 219, 14

Vrsta, podvrsta i kategorija rada
Radovi u časopisima, članak, znanstveni

Ključne riječi
serotonin transporter ; rat model ; obesity ; hypothalamus ; body weight homeostasis ; energy balance

Sažetak
Central and peripheral pools of biogenic monoamine serotonin (5-hydroxytryptamine [5HT]) exert opposite effects on the body weight regulation: increase in brain 5HT activity is expected to decrease body weight, whereas increase in peripheral 5HT activity will increase body weight and adiposity. In a genetic model of rats with constitutionally high- or low-5HT homeostasis (hyperserotonergic/hyposerotonergic rats), we have studied how individual differences in endogenous 5HT tone modulate net energy balance of the organism. The high-5HT and low-5HT sublines of the model were developed by selective breeding toward extreme platelet activities of 5HT transporter, a key molecule determining 5HT bioavailability/activity. In animals from high-5HT and low-5HT sublines, we assessed physiological characteristics associated with body weight homeostasis and expression profile of a large scale of body weight–regulating genes in hypothalamus, a major brain region controlling energy balance. Results showed that under standard chow diet animals from the high-5HT subline, as compared to low- 5HT animals, have lifelong increased body weight (by 12%), higher absolute daily food intake (by 9%), and different pattern of fat distribution (larger amount of white adipose tissue and lower amount of brown adipose tissue). A large number of body weight–regulating hypothalamic genes were analyzed for their mRNA expression: 24 genes by reverse transcription–quantitative polymerase chain reaction (n = 9–10 rats/subline) including neuropeptides and their receptors, growth factors, transcriptional factors, and receptors for peripheral signals, and a total of 84 genes of various classes by polymerase chain reaction array (pools of six rats/subline). Only few genes showed significant differences in mRNA expression levels between 5HT sublines (e.g. neuropeptide Y receptor, fibroblast growth factor 10), but high-5HT animals displayed a clear trend to upregulation of mRNAs for a number of orexigenic signaling peptides, their receptors, and other molecules with orexigenic activity. Receptors for peripheral signals (leptin, insulin) and molecules in their downstream signaling were not altered, indicating no changes in central insulin/leptin resistance. At the protein level, there were no differences in the content of hypothalamic leptin receptor between 5HT sublines, but significant sex and age effects were observed. Results show that higher constitutive/individual 5HT tone favors higher body weight and adiposity probably due to concurrent upregulation of several hypothalamic orexigenic pathways.

Izvorni jezik
Engleski

Znanstvena područja
Biologija



POVEZANOST RADA


Projekt / tema
HRZZ-IP-2014-09-7827 - Serotonergična modulacija pretilosti: međuovisnost regulatornih molekula i puteva (Lipa Čičin-Šain, )

Ustanove
Institut "Ruđer Bošković", Zagreb

Citiraj ovu publikaciju

Kesić, Maja; Baković, Petra; Horvatiček, Marina; Proust, Bastien Lucien Jean; Štefulj, Jasminka; Čičin-Šain, Lipa
Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis // Frontiers in neuroscience, 14 (2020), 219, 14 doi:10.3389/fnins.2020.00219 (međunarodna recenzija, članak, znanstveni)
Kesić, M., Baković, P., Horvatiček, M., Proust, B., Štefulj, J. & Čičin-Šain, L. (2020) Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis. Frontiers in neuroscience, 14, 219, 14 doi:10.3389/fnins.2020.00219.
@article{article, year = {2020}, pages = {14}, DOI = {10.3389/fnins.2020.00219}, chapter = {219}, keywords = {serotonin transporter, rat model, obesity, hypothalamus, body weight homeostasis, energy balance}, journal = {Frontiers in neuroscience}, doi = {10.3389/fnins.2020.00219}, volume = {14}, issn = {1662-453X}, title = {Constitutionally High Serotonin Tone Favors Obesity: Study on Rat Sublines With Altered Serotonin Homeostasis}, keyword = {serotonin transporter, rat model, obesity, hypothalamus, body weight homeostasis, energy balance}, chapternumber = {219} }

Časopis indeksira:


  • Web of Science Core Collection (WoSCC)
    • Science Citation Index Expanded (SCI-EXP)
    • SCI-EXP, SSCI i/ili A&HCI
  • Scopus


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