Glucocorticoid treatment increases density of serotonin 5-HT2A receptors in humans

Kling, Anders; Mjörndal, Tom; Rantapää-Dahlqvist, Solbritt

doi:10.1016/j.psyneuen.2012.10.006

Cited by 3 publications

(2 citation statements)

References 54 publications

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“…Besides GCs can directly enhance FA synthase to promote FA synthesis in liver 34 , 35 , indirect GC effects on hepatic lipogenesis are to induce adipose tissue lipolysis, which results in high FFAs level in the blood and delivering FFAs to liver, and systemic hyperinsulinemia and hyperglycemia, all of which drive hepatic DNL 36 . For the impact of GCs on 5-HT system, it is found that GC treatment can increase density of serotonin 5-HT2A receptors in humans 37 , and induces a tissue-specific regulation of Tph mRNA levels in the pineal gland 38 .…”

Section: Discussionmentioning

confidence: 99%

Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver

Fu¹,

Ma²,

Li³

et al. 2016

Int. J. Biol. Sci.

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Hepatic triglycerides production and adipose lipolysis are pivotal for long-term stress (LTS) or hyperglucocorticoidemia-induced insulin resistance. 5-hydroxytryptamine (5-HT) has been demonstrated to induce hepatic lipid metabolic abnormality by activating mammalian target of rapamycin (mTOR). In present study, we explored whether 5-HT is involved in LTS effects in liver using restraint stress-exposed rats and cultured primary rat hepatocytes and HepG2 cells. LTS with hyperglucocorticoidemia induced hepatic 5-HT synthetic increase with tryptophan hydroxylase 1 (Tph1) up-regulation, and 5-HT2 receptor (5-HT2R, including 5-HT2A, 2B receptor) up-regulation in liver and visceral adipose, as well as hepatic mTOR activation with triglycerides and VLDL overproduction with steatosis, and visceral adipose lipolytic increase with high blood free fatty acids (FFAs) level. 5-HT exposure exhibited LTS-like effects in both tissues, and both LTS and 5-HT effects could be abolished significantly by blocking 5-HT2R. In HepG2 cells dexamethasone or palmitate-induced mTOR activation with triglycerides and VLDL overproduction were accompanied by up-regulations of 5-HT synthesis and 5-HT2R, which were significantly abolished by gene silencing Tph1 or 5-HT2R and were almost fully abolished by co-silencing of both, especially on VLDL overproduction. Chemical inhibition of Tph1 or/and 5-HT2R in both hepatocytes exhibited similar abolishment with genetic inhibition on dexamethason-induced effects. 5-HT-stimulated effects in both hepatocytes were fully abolished by blocking 5-HT2R, while 5-HT itself also up-regulated 5-HT2R. In conclusion, up-regulated hepatic 5-HT synthesis and 5-HT2R induced by both glucocorticoid and FFAs are crucial for LTS-induced hepatic steatosis with VLDL overproduction, while 5-HT by acting on 5-HT2R mediates mTOR activation in liver.

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Section: Discussionmentioning

confidence: 99%

Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver

Fu¹,

Ma²,

Li³

et al. 2016

Int. J. Biol. Sci.

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show abstract

“…Therefore, glucose metabolism and obesity might be etiologically associated with 5‐HT, as well as adipocyte differentiation mediated by 5‐HT 2 Rs in vitro . Upregulation of the 5‐HT 2A R is often found in obesity and diabetes, which leads to high blood sugar level, and GC treatment can increase density of serotonin 5‐HT 2A R in humans.…”

Section: Introductionmentioning

confidence: 99%

Effective treatment with combination of peripheral 5‐hydroxytryptamine synthetic inhibitor and 5‐hydroxytryptamine 2 receptor antagonist on glucocorticoid‐induced whole‐body insulin resistance with hyperglycemia

Guo

et al. 2016

J of Diabetes Invest

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Aims/IntroductionOur previous study found that dexamethasone‐induced insulin resistance (IR) was involved in 5‐hydroxytryptamine (5‐HT) synthesis and 5‐hydroxytryptamine 2 receptor (5‐HT 2R) in the periphery. The present study examined the effects of inhibitions of both peripheral 5‐HT synthesis and 5‐HT 2R on dexamethasone‐induced IR.Materials and MethodsMale rats were exposed to dexamethasone for 10 days, then treated with or without a 5‐HT 2R antagonist, sarpogrelate, a 5‐HT synthetic inhibitor, carbidopa, alone or in combination for 20 days.ResultsDexamethasone‐induced whole‐body IR, with glucose intolerance, decreased insulin sensitivity, hyperglycemia, hyperinsulinemia and dyslipidemia, could be effectively abolished by sarpogrelate or/and carbidopa, whereas IR‐related actions of dexamethasone in tissues were accompanied by increased 5‐HT synthesis in the liver and visceral adipose, and upregulated 5‐HT 2R (5‐HT 2 AR and 5‐HT 2 BR) expression in these two tissues as well as in skeletal muscle. Sarpogrelate or/and carbidopa treatment significantly abolished dexamethasone‐caused tissue‐specific IR. In the liver, increased gluconeogenesis, triglycerides and very low‐density lipoprotein syntheses with steatosis, and downregulated expression of plasmalemmal glucose transporter‐2 were markedly reversed. In the visceral adipose and skeletal muscle, downregulated expression of plasmalemmal glucose transporter‐4 was significantly reversed, and increased lipolysis was also reversed in the visceral adipose. Dexamethasone‐induced activations of hepatic mammalian target of rapamycin serine2448, and S6K threonine389/412 phosphorylation were also abolished markedly by sarpogrelate or/and carbidopa. Co‐treatment with sarpogrelate and carbidopa showed a synergistic effect on suppressing dexamethasone actions.ConclusionInhibitions of both peripheral 5‐HT synthesis and 5‐HT 2R are expected to be a dependable target for treatment of steroid‐induced diabetes.

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Psychedelic Psychiatry

Bender,

Siegel

2024

Reference Module in Neuroscience and Biobehavioral Psychology

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Glucocorticoid treatment increases density of serotonin 5-HT2A receptors in humans

Cited by 3 publications

References 54 publications

Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver

Long-term Stress with Hyperglucocorticoidemia-induced Hepatic Steatosis with VLDL Overproduction Is Dependent on both 5-HT2 Receptor and 5-HT Synthesis in Liver

Effective treatment with combination of peripheral 5‐hydroxytryptamine synthetic inhibitor and 5‐hydroxytryptamine 2 receptor antagonist on glucocorticoid‐induced whole‐body insulin resistance with hyperglycemia

Psychedelic Psychiatry

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