Decreased 5‐HT2cR and GHSR1a interaction in antipsychotic drug‐induced obesity

Huang, Xu‐Feng; Weston–Green, Katrina; Yu, Yinghua

doi:10.1111/obr.12638

Cited by 18 publications

(12 citation statements)

References 91 publications

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“…To the best of our knowledge, the present study is the first to report that 95% of 5‐HT2c receptors overlapped with NPY‐GFP neurons in the Arc. Risperidone is a potent 5‐HT2c receptor antagonist, and previous studies have demonstrated that obesogenic antipsychotic drugs reduce 5‐HT2c receptor inhibition of GSHR1a . Therefore, our results indicate that risperidone may selectively stimulate NPY expression in the Arc by reducing 5‐HT2c receptor activity, thereby increasing food intake.…”

Section: Discussionsupporting

confidence: 63%

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Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5‐HT2c receptor—NPY pathway

et al. 2019

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Aims: Many patients taking risperidone for the treatment of psychiatric disorders experience substantial body weight gain. Researchers have speculated that risperidone induces obesity by modulating central signals; however, the precise central mechanisms involved remain to be fully elucidated.Methods: Twenty-four C57BL/6J mice were divided into four groups: a control group; a risperidone-treated group; a lorcaserin-treated group; and a combined risperidone + lorcaserin-treated group. The mice were received the corresponding treatments for 4 weeks, and their brains were collected for in situ hybridization analysis. A subset of C57BL/6J mice was administrated with risperidone or placebo, and brains were collected 60 minutes post-treatment for determination of c-fos activity. In addition, brains of NPY-GFP mice treated with or without risperidone were collected to perform colocalization of NPY and c-fos, as well as NPY and 5-HT2c receptor using immunohistochemistry. Results:There was significantly elevated c-fos expression in the hypothalamic arcuate nucleus (Arc) of risperidone-treated mice. More than 68% c-fos-positive neurons were NPY-expressing neurons. Furthermore, in situ hybridization revealed that Arc NPY mRNA expression was significantly increased in the risperidone-treated group compared with control group. Moreover, we identified that 95% 5-HT2c receptors were colocalized with NPY positive neurons, and increased Arc NPY mRNA expression induced by risperidone was markedly reduced by cotreatment with lorcaserin, a specific 5-HT2c receptor agonist. Conclusion:Our findings provide critical insight into the mechanisms underlying antipsychotic-induced obesity, which may assist the development of therapeutic strategies to address metabolic side effects of risperidone. K E Y W O R D S5-HT2c receptor, hypothalamic arcuate nucleus (Arc), NPY, obesity, risperidone

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Section: Discussionsupporting

confidence: 63%

“…In contrast to their non‐obesogenic counterparts, obesogenic SGAs are commonly associated with potent 5‐HT2c receptor antagonism . A previous study reported that 5‐HT2c receptors can inhibit the expression of orexigenic growth hormone secretagogue receptor 1a (GHSR1a) in the hypothalamus .…”

Section: Introductionmentioning

confidence: 99%

Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5‐HT2c receptor—NPY pathway

et al. 2019

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“…5‐HT2C receptors can increase inositol triphosphate (IP3) and diacylglycerol, open calcium channels, and release calcium stores, which promote neurite growth . 5‐HT2C receptors have nonedited and edited forms . The edited isoform of 5‐HT2C receptor has a suppressive effect on neurite growth, which could be reversed by a 5‐HT2C receptor inverse agonist .…”

Section: Antipsychotic Drug‐targeted Receptors Regulate Neurites In Smentioning

confidence: 99%

Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment

Huang

Song

2018

Medicinal Research Reviews

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Although antipsychotic drugs are mainly used for treating schizophrenia, they are widely used for treating various psychiatric diseases in adults, the elderly, adolescents and even children. Today, about 1.2% of the worldwide population suffers from psychosis and related disorders, which translates to about 7.5 million subjects potentially targeted by antipsychotic drugs. Neurites project from the cell body of neurons and connect neurons to each other to form neural networks. Deficits in neurite outgrowth and integrity are implicated in psychiatric diseases including schizophrenia. Neurite deficits contribute to altered brain development, neural networking and connectivity as well as symptoms including psychosis and altered cognitive function. This review revealed that (1) antipsychotic drugs could have profound effects on neurites, synaptic spines and synapse, by which they may influence and regulate neural networking and plasticity; (2) antipsychotic drugs target not only neurotransmitter receptors but also intracellular signaling molecules regulating the signaling pathways responsible for neurite outgrowth and maintenance; (3) high doses and chronic administration of antipsychotic drugs may cause some loss of neurites, synaptic spines, or synapsis in the cortical structures. In addition, confounding effects causing neurite deficits may include elevated inflammatory cytokines and antipsychotic drug-induced metabolic side effects in patients on chronic antipsychotic therapy. Unraveling how antipsychotic drugs affect neurites and neural connectivity is essential for improving therapeutic outcomes and preventing aversive effects for patients on antipsychotic drug treatment.

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“…Interestingly, some researchers have suggested that weight gain and other metabolic effects may be linked to the improvement of symptoms ( 3 ). These side effects are most likely related to the high affinity of these compounds for other receptor systems in the brain, which are involved in regulation of appetite and food intake ( 4 – 6 ). Such effects can have a deleterious impact on the overall health of patients and can potentially lead to conditions such as insulin resistance, type 2 diabetes, obesity, and cardiovascular complications ( 7 , 8 ).…”

Section: Introductionmentioning

confidence: 99%

Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients

et al. 2018

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This is the first study to identify lipidomic markers in plasma associated with response of acutely ill schizophrenia patients in response to specific antipsychotic treatments. The study population included 54 schizophrenia patients treated with antipsychotics for 6 weeks. Treatment led to significant improvement in positive and negative symptoms for 34 patients with little or no improvement for 20 patients. In addition, 37 patients showed an increase in body mass index after the 6 week treatment period, consistent with effects on metabolism and the association of such effects with symptom improvement. Profiling of plasma samples taken prior to therapy using liquid chromatography tandem mass spectrometry (LC-MS/MS) resulted in identification of 38, 10, and 52 compounds associated with the olanzapine, risperidone, and quetiapine treatment groups, which could be used to distinguish responders from non-responders. Limitations include the retroactive active nature of the study and the small sample size. Further investigations with larger sample sets could lead to the development of a molecular test that could be used to help psychiatrists determine the best treatment options for each patient.

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Decreased 5‐HT2cR and GHSR1a interaction in antipsychotic drug‐induced obesity

Cited by 18 publications

References 91 publications

Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5‐HT2c receptor—NPY pathway

Risperidone stimulates food intake and induces body weight gain via the hypothalamic arcuate nucleus 5‐HT2c receptor—NPY pathway

Effects of antipsychotic drugs on neurites relevant to schizophrenia treatment

Blood-Based Lipidomics Approach to Evaluate Biomarkers Associated With Response to Olanzapine, Risperidone, and Quetiapine Treatment in Schizophrenia Patients

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