Metabolic Disturbances in Rat Sublines with Constitutionally Altered Serotonin Homeostasis

Kesić, Maja; Baković, Petra; Stojković, Ranko; Štefulj, Jasminka; Čičin‐Šain, Lipa

doi:10.3390/ijms22105400

Cited by 4 publications

(15 citation statements)

References 78 publications

(134 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Nevertheless, our results support the proposed role of 5HT signaling in regulating total weight gain in response to a hypercaloric diet. Recently, it was also shown that in mice fed standard chow, the upregulation of 5HT signaling promotes weight gain [57], consistent with basal phenotypic differences in our 5HT-sublines [33].…”

Section: Discussionsupporting

confidence: 89%

“…High-5HT animals fed a standard diet exhibit glucose intolerance and insulin resistance compared to low-5HT animals [33]. Since HFD did not significantly affect the performance of high-5HT animals in GTT and ITT, they appear to have developed the coping mechanisms that prevent further deterioration of glucose homeostasis.…”

Section: Discussionmentioning

confidence: 91%

“…Our previous studies on the WZ-5HT rat model have shown that constitutionally high whole-body 5HT tone is associated with increased body weight and adiposity, as well as impaired glucose and lipid metabolism [32,33,42]. In the present study, we showed that the consumption of a high-fat diet resulted in weight gain and increased insulin resistance only in the low-5HT animals, while the high-5HT animals were protected from most metabolic disturbances in the presence of obesogenic diet.…”

Section: Discussionmentioning

confidence: 99%

“…Using a genetic model of rats with constitutionally altered 5HT homeostasis (Wistar-Zagreb 5HT, WZ-5HT rats) we have previously shown that constitutional 5HT tone is a potent endogenous determinant of energy balance [32,33]. Two sublines of the WZ-5HT rat model, the high-5HT and low-5HT sublines, were developed by selective breeding of rats towards the extremes of platelet 5HT level and platelet 5HTT activity [34][35][36][37].…”

Section: Introductionmentioning

confidence: 99%

“…Further neurochemical, pharmacological and behavioral studies showed that genetic selection for platelet 5HT parameters resulted in differences in the functioning of both the peripheral and central 5HT systems, with animals from the high-5HT subline having constitutionally higher whole-body 5HT tone than animals from the low-5HT subline [37][38][39][40][41][42]. On a standard diet, high 5HT animals exhibited higher body weight, increased adiposity and impaired glucose homeostasis compared to low 5HT animals [32,33].…”

Section: Introductionmentioning

confidence: 99%

See 4 more Smart Citations

Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone

Baković

Kesić

Kolarić

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

Maintaining energy balance is a complex physiological function whose dysregulation can lead to obesity and associated metabolic disorders. The bioamine serotonin (5HT) is an important regulator of energy homeostasis, with its central and peripheral pools influencing energy status in opposing ways. Using sublines of rats with constitutionally increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, we have previously shown that under standard diet constitutionally higher 5HT activity is associated with increased body weight, adiposity, and impaired glucose homeostasis. Here, we investigated the response of 5HT sublines to an obesogenic diet. Consistent with previous findings, high-5HT animals fed a standard diet had poorer metabolic health. However, in response to a high-fat diet, only low-5HT animals increased body weight and insulin resistance. They also showed more pronounced changes in blood metabolic parameters and the expression of various metabolic genes in hypothalamus and adipose tissue. On the other hand, high-5HT animals appeared to be protected from major metabolic disturbances of the obesogenic diet. The results suggest that constitutionally low 5HT activity is associated with higher susceptibility to harmful effects of a high-energy diet. High-5HT subline, which developed less adverse metabolic outcomes on hypercaloric diets, may prove useful in understanding metabolically healthy obesity in humans.

show abstract

Section: Discussionsupporting

confidence: 89%

Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 3 more Smart Citations

Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone

Baković

Kesić

Kolarić

et al. 2023

IJMS

Self Cite

View full text Add to dashboard Cite

show abstract

Increased gut serotonin production in response to bisphenol A structural analogs may contribute to their obesogenic effects

Barra

Kwon

Morrison

et al. 2022

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Obesogens are synthetic, environmental chemicals that can disrupt endocrine control of metabolism and contribute to the risk of obesity and metabolic disease. Bisphenol A is one of the most studied obesogens. There is considerable evidence that BPA exposure is associated with weight gain, increased adiposity, poor blood glucose control and non-alcoholic fatty liver disease in animal models and human populations. Increased usage of structural analogues of BPA has occurred in response to legislation banning their use in some commercial products. However, BPA analogues may also cause some of the same metabolic impairments because of common mechanisms of action. One key effector that is altered by BPA and its analogues is serotonin, however it is unknown if BPA-induced changes in peripheral serotonin pathways underlie metabolic perturbations seen with BPA exposure. Upon ingestion, BPA and its analogues act as endocrine disrupting chemicals in the gastrointestinal tract to influence serotonin production by the gut, where over 95% of serotonin is produced. The purpose of this review is to evaluate how BPA and its analogues alter gut serotonin regulation and then discuss how disruption of serotonergic networks influence host metabolism. We also provide evidence that BPA and its analogues enhance serotonin production in gut enterochromaffin cells. Taken together, we propose that BPA and many BPA analogues represent endocrine disrupting chemicals that can influence host metabolism through the endogenous production of gut derived factors, such as serotonin.

show abstract

Constitutive Serotonin Tone as a Modulator of Brown Adipose Tissue Thermogenesis: A Rat Study

Kesić

Baković

Farkaš

et al. 2023

Life

Self Cite

View full text Add to dashboard Cite

Brown adipose tissue (BAT), an important regulator of thermogenic and metabolic processes, is considered a promising target to combat metabolic disorders. The neurotransmitter and hormone serotonin (5HT) is a major modulator of energy homeostasis, with its central and peripheral pools acting in opposing ways. To better understand how individual variations in 5HT homeostasis influence the thermogenic functionality of BAT, we used a rat model consisting of two sublines with constitutively increased (high-5HT) or decreased (low-5HT) whole-body 5HT tone, developed by selective breeding for platelet 5HT parameters. We have shown that animals with constitutively low 5HT activity maintained at a standard housing temperature (22 °C) have greater interscapular BAT (iBAT) mass and higher iBAT metabolic activity (as evidenced by measurements of iBAT temperature and glucose uptake), accompanied by increased iBAT mRNA expression of key thermogenic genes, compared to animals with high 5HT tone. In response to further thermogenic challenges—intermittent cold exposure or treatment with a β3-adrenergic agonist—5HT sublines show several functional and molecular differences linking constitutively low endogenous 5HT tone to higher BAT activity/capacity. Overall, the results support a role of 5-HT in the control of BAT thermogenesis They also suggest that individuals with lower 5HT activity may be more sensitive to β3-adrenergic drugs.

show abstract

Metabolic Disturbances in Rat Sublines with Constitutionally Altered Serotonin Homeostasis

Cited by 4 publications

References 78 publications

Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone

Metabolic and Molecular Response to High-Fat Diet Differs between Rats with Constitutionally High and Low Serotonin Tone

Increased gut serotonin production in response to bisphenol A structural analogs may contribute to their obesogenic effects

Constitutive Serotonin Tone as a Modulator of Brown Adipose Tissue Thermogenesis: A Rat Study

Contact Info

Product

Resources

About