Serotonin (5-HT) and 5-HT2A receptor agonists suppress lipolysis in primary rat adipose cells

Hansson, Björn; Medina, Anya; Fryklund, Claes; Fex, Malin; Stenkula, Karin G.

doi:10.1016/j.bbrc.2016.04.110

Cited by 23 publications

(18 citation statements)

References 35 publications

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“…In this study, 5-HT2a expression levels were compared between control rats and CUMS rats, and was consistent with previous research where mice subjected to chronic stress had increased 5-HT 2AR (Tianzhu et al, 2014). Recently, it has been suggested that 5 HT2AR concentration in platelet lysate is involved the pathology of depression (Liu et al, 2015) and 5-HT2a could contribute to altered systemic lipid- and glucose metabolism (Hansson et al, 2016). In accordance with a study that revealed 5-HT2A receptor antagonist treatment being able to reverse depressive-like behaviors (Xu et al, 2016), our results showed that both miR-16 and Fluoxetine treatments can decrease 5-HT2A levels and attenuate depressive behavior in rats.…”

Section: Discussionmentioning

confidence: 99%

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

Yang

et al. 2017

Front. Neurosci.

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In the clinic selective serotonin reuptake inhibitors (SSRIs), like Fluoxetine, remain the primary treatment for major depression. It has been suggested that miR-16 regulates serotonin transporters (SERT) via raphe nuclei and hippocampal responses to antidepressants. However, the underlying mechanism and regulatory pathways are still obtuse. Here, a chronic unpredicted mild stress (CUMS) depression model in rats was established, and then raphe nuclei miR-16 and intragastric Fluoxetine injections were administered for a duration of 3 weeks. An open field test and sucrose preference quantification displayed a significant decrease in the CUMS groups when compare to the control groups, however these changes were attenuated by both miR-16 and Fluoxetine treatments. A dual-luciferase reporter assay system verified that hsa-miR-16 inhibitory effects involve the targeting of 3′UTR on the 5-HTT gene. Expression levels of miR-16 and BDNF in the hippocampus were examined with RT-PCR, and it was found that increased 5-HT2a receptor expression induced by CUMS can be decreased by miR-16 and Fluoxetine administration. Immunofluorescence showed that expression levels of neuron NeuN and MAP-2 in CUMS rats were lower. Apoptosis and autophagy levels were evaluated separately through relative expression of Bcl-2, Caspase-3, Beclin-1, and LC3II. Furthermore, CUMS was found to decrease levels of hippocampal mTOR, PI3K, and AKT. These findings indicate that apoptosis and autophagy related pathways could be involved in the effectiveness of antidepressants, in which miR-16 participates in the regulation of, and is likely to help integrate rapid therapeutic strategies to alleviate depression clinically. These findings indicate that miR-16 participates in the regulation of apoptosis and autophagy and could account for some part of the therapeutic effect of SSRIs. This discovery has the potential to further the understanding of SSRIs and accelerate the development of new treatments for depression.

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Section: Discussionmentioning

confidence: 99%

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

Yang

et al. 2017

Front. Neurosci.

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“…We observed mildly enhanced circulating glucose levels in the 5-

H T_{2 A}^{- / -}

mice in our serum profile studies, with a genotype effect noted in both male and female mice. Recent reports using pharmacological approaches indicate a role for peripheral 5-HT 2A receptors in the liver and in adipocytes in mediating metabolic changes evoked by chronic stress, including dyslipidemia and insulin resistance (Fu et al., 2016, Hansson et al., 2016, Oh et al., 2016, Rosmond et al., 2002). Chronic stress is associated with upregulation of liver 5-HT 2A and 5-HT 2B receptors, and a 5-HT 2A/B receptor antagonist sarpogrelate can block stress-evoked dyslipidemia (Fu et al., 2016).…”

Section: Discussionmentioning

confidence: 99%

5-HT 2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

Jaggar

Weisstaub

Gingrich

2017

Neurobiology of Stress

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Chronic stress enhances risk for psychiatric disorders, and in animal models is known to evoke depression-like behavior accompanied by perturbed neurohormonal, metabolic, neuroarchitectural and transcriptional changes. Serotonergic neurotransmission, including serotonin2A (5-HT2A) receptors, have been implicated in mediating specific aspects of stress-induced responses. Here we investigated the influence of chronic unpredictable stress (CUS) on depression-like behavior, serum metabolic measures, and gene expression in stress-associated neurocircuitry of the prefrontal cortex (PFC) and hippocampus in 5-HT2A receptor knockout (5-HT2A−/−) and wild-type mice of both sexes. While 5-HT2A−/− male and female mice exhibited a baseline reduced anxiety-like state, this did not alter the onset or severity of behavioral despair during and at the cessation of CUS, indicating that these mice can develop stress-evoked depressive behavior. Analysis of metabolic parameters in serum revealed a CUS-evoked dyslipidemia, which was abrogated in 5-HT2A−/− female mice with a hyperlipidemic baseline phenotype. 5-HT2A−/− male mice in contrast did not exhibit such a baseline shift in their serum lipid profile. Specific stress-responsive genes (Crh, Crhr1, Nr3c1, and Nr3c2), trophic factors (Bdnf, Igf1) and immediate early genes (IEGs) (Arc, Fos, Fosb, Egr1-4) in the PFC and hippocampus were altered in 5-HT2A−/− mice both under baseline and CUS conditions. Our results support a role for the 5-HT2A receptor in specific metabolic and transcriptional, but not behavioral, consequences of CUS, and highlight that the contribution of the 5-HT2A receptor to stress-evoked changes is sexually dimorphic.

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“…5-HT 2A receptors are distributed in cardiovascular smooth muscle cells and platelets and contribute to vasoconstriction and aggregation, respectively (Kaumann and Levy, 2006). Rat adipose tissue has also been reported to bear 5-HT 2A receptors, which suppress lipolysis by b-adrenergic stimulation (Hansson et al, 2016). Recently, Crane et al (2015) formulated a novel theory regarding the association between BAT thermogenesis and peripheral serotonin levels.…”

Section: Introductionmentioning

confidence: 99%

5-HT_2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT_2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature

Nakamura

Shintani-Ishida

Ikegaya

2018

J Pharmacol Exp Ther

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Recreational drugs such as 3,4-methylenedioxymethamphetamine and cocaine induce hyperthermia, which is affected by ambient temperature. 2-(4-Bromo-2,5-dimethoxyphenyl)--(2-methoxybenzyl)ethanamine (25B-NBOMe), a selective agonist of 5-HT receptor used as a recreational drug, reportedly induces hyperthermia. This study aimed to verify whether 25B-NBOMe induces ambient temperature-dependent hyperthermia and to clarify its mechanism. Eight-week-old male Sprague-Dawley rats were administered intraperitoneal injection of 25B-NBOMe at an ambient temperature of 23°C or 29°C. 25B-NBOMe administration at 23°C did not change the core body temperature of the rats, whereas administration at 29°C induced significant hyperthermia 30-120 minutes postadministration. Tail surface temperature temporarily decreased 30 minutes postadministration, indicating heat storage by peripheral vasoconstriction despite a high ambient temperature. Because 25B-NBOMe-induced-hyperthermia was suppressed by sarpogrelate, but not by destruction of central noradrenaline or serotonin neurons, peripheral 5-HT receptors were considered contributors to the development of hyperthermia at a high ambient temperature, independently from central neurons. The temperature of brown adipose tissue (BAT) increased 60-120 minutes postadministration of 25B-NBOMe at 29°C, indicating thermogenesis. Previous studies have reported that peripheral serotonin contributes to the inhibition of BAT thermogenesis. Decreased plasma serotonin levels were observed at 29°C, and serotonin administration partially suppressed 25B-NBOMe-induced hyperthermia at a high ambient temperature, suggesting that decreased levels of peripheral serotonin induced BAT thermogenesis. Our findings indicate that 25B-NBOMe induces hyperthermia at a high ambient temperature via vasoconstriction regulated by 5-HT receptors and BAT thermogenesis mediated by decreased levels of plasma serotonin. Thus, peripheral serotonin plays a partial but important role in thermoregulation.

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Serotonin (5-HT) and 5-HT2A receptor agonists suppress lipolysis in primary rat adipose cells

Cited by 23 publications

References 35 publications

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

5-HT 2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

5-HT_2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT_2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature

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Serotonin (5-HT) and 5-HT2A receptor agonists suppress lipolysis in primary rat adipose cells

Cited by 23 publications

References 35 publications

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

miR-16 and Fluoxetine Both Reverse Autophagic and Apoptotic Change in Chronic Unpredictable Mild Stress Model Rats

5-HT 2A receptor deficiency alters the metabolic and transcriptional, but not the behavioral, consequences of chronic unpredictable stress

5-HT2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature

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5-HT_2A Receptor Agonist-Induced Hyperthermia Is Induced via Vasoconstriction by Peripheral 5-HT_2A Receptors and Brown Adipose Tissue Thermogenesis by Peripheral Serotonin Loss at a High Ambient Temperature