Atypical Antipsychotics and the Human Skeletal Muscle Lipidome

Burghardt, Kyle J.; Ward, Kristen M.; Sanders, Elani; Howlett, Bradley H.; Seyoum, Berhane; Yi, Zhengping

doi:10.3390/metabo8040064

Cited by 5 publications

(7 citation statements)

References 79 publications

(98 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In addition, lipidomic studies on lipid contents (e.g., FFA, phosphatidylcholines and ceramides) in skeletal muscle biopsies from patients treated with AAPs have found several differences compared to the general population with potential consequences in insulin resistance; conversely, mood stabilizers did not cause the same shift [ 106 ].…”

Section: Effects Of Aaps On Hypothalamus and Peripheral Tissuesmentioning

confidence: 99%

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

et al. 2021

View full text Add to dashboard Cite

Atypical antipsychotics (AAPs) are commonly prescribed medications to treat schizophrenia, bipolar disorders and other psychotic disorders. However, they might cause metabolic syndrome (MetS) in terms of weight gain, dyslipidemia, type 2 diabetes (T2D), and high blood pressure, which are responsible for reduced life expectancy and poor adherence. Importantly, there is clear evidence that early metabolic disturbances can precede weight gain, even if the latter still remains the hallmark of AAPs use. In fact, AAPs interfere profoundly with glucose and lipid homeostasis acting mostly on hypothalamus, liver, pancreatic β-cells, adipose tissue, and skeletal muscle. Their actions on hypothalamic centers via dopamine, serotonin, acetylcholine, and histamine receptors affect neuropeptides and 5′AMP-activated protein kinase (AMPK) activity, thus producing a supraphysiological sympathetic outflow augmenting levels of glucagon and hepatic glucose production. In addition, altered insulin secretion, dyslipidemia, fat deposition in the liver and adipose tissues, and insulin resistance become aggravating factors for MetS. In clinical practice, among AAPs, olanzapine and clozapine are associated with the highest risk of MetS, whereas quetiapine, risperidone, asenapine and amisulpride cause moderate alterations. The new AAPs such as ziprasidone, lurasidone and the partial agonist aripiprazole seem more tolerable on the metabolic profile. However, these aspects must be considered together with the differences among AAPs in terms of their efficacy, where clozapine still remains the most effective. Intriguingly, there seems to be a correlation between AAP’s higher clinical efficacy and increase risk of metabolic alterations. Finally, a multidisciplinary approach combining psychoeducation and therapeutic drug monitoring (TDM) is proposed as a first-line strategy to avoid the MetS. In addition, pharmacological treatments are discussed as well.

show abstract

Section: Effects Of Aaps On Hypothalamus and Peripheral Tissuesmentioning

confidence: 99%

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

et al. 2021

View full text Add to dashboard Cite

show abstract

“…Smesny et al reported a decrease in total ceramide levels in the skin of patients suffering from first-episode schizophrenia [ 26 ]. In contrast, total ceramide levels increased in the skeletal muscle of SGA-treated patients compared with those in the mood stabilizer group [ 16 ]. In preclinical studies, mice chronically treated with haloperidol showed a decline in brain sphinganine, a lipid intermediate in ceramide synthesis [ 27 ].…”

Section: Discussionmentioning

confidence: 99%

“…Given the critical roles of lipids in cellular mechanisms, lipid analysis may help understand the efficacy and side effects of antipsychotic treatments. Several studies have assessed the role of phospholipids and sphingolipids in the structure and function of cellular membranes in schizophrenia before and after antipsychotic treatment [ 15 , 16 , 17 , 18 , 19 ]. Ceramides and other sphingolipids are the main components of lipid rafts in plasma membranes, where they act as structural and signaling molecules [ 20 ].…”

Section: Introductionmentioning

confidence: 99%

The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo

Canfrán‐Duque

Pastor

García-Seisdedos

et al. 2021

IJMS

View full text Add to dashboard Cite

Atypical or second-generation antipsychotics are used in the treatment of psychosis and behavioral problems in older persons with dementia. However, these pharmaceutical drugs are associated with an increased risk of stroke in such patients. In this study, we evaluated the effects of risperidone treatment on phospholipid and sphingolipid composition and lipid raft function in peripheral blood mononuclear cells (PBMCs) of older patients (mean age >88 years). The results showed that the levels of dihydroceramides, very-long-chain ceramides, and lysophosphatidylcholines decreased in PBMCs of the risperidone-treated group compared with untreated controls. These findings were confirmed by in vitro assays using human THP-1 monocytes. The reduction in the levels of very-long-chain ceramides and dihydroceramides could be due to the decrease in the expression of fatty acid elongase 3, as observed in THP-1 monocytes. Moreover, risperidone disrupted lipid raft domains in the plasma membrane of PBMCs. These results indicated that risperidone alters phospholipid and sphingolipid composition and lipid raft domains in PBMCs of older patients, potentially affecting multiple signaling pathways associated with these membrane domains.

show abstract

“…12 Significantly, AAPs have a higher propensity to cause MetS, when compared with TAPs, with clozapine and olanzapine being the most concerning, 13 and AAPs appear to cause insulin resistance and weight gain independently of the occurrence of psychiatric disease. 14 Despite the known adverse effects of AAPs on MetS, which predisposes these patients to cardiovascular risk factors, there is an overall positive effect of AAPs use on all-cause as well as cardiac mortality in patients undergoing treatment, as mentioned before. 4,5 This finding might be a result of the positive effects of AAPs in reducing the overall symptom load of the mental illness, resulting in patients seeking better help for behavioral or lifestyle choices, including substance use.…”

Section: Introductionmentioning

confidence: 87%

“…A recent study found that AAPs induce changes in lipid profiles in human skeletal muscle biopsies from bipolar patients, when compared to mood stabilizers (higher total fatty acids and phosphatidylcholines levels and lower ceramides levels) and that these changes correlate with insulin sensitivity. 14 4.6 | Effects of AAPs on the intestine…”

Section: Lipid Contentmentioning

confidence: 99%

Metabolic effects of atypical antipsychotics: Molecular targets

Fonseca,

Carmo,

Martel

2023

J Neuroendocrinology

View full text Add to dashboard Cite

Atypical antipsychotics (AAPs) are commonly prescribed drugs in the treatment of schizophrenia, bipolar disorder and other mental diseases with psychotic traits. Although the use of AAPs is associated with beneficial effects in these patients, they are also associated with undesired metabolic side effects, including metabolic syndrome (MetS). MeS is defined by the presence of metabolic abnormalities such as large waist circumference, dyslipidemia, fasting hyperglycemia and elevated blood pressure, which predispose to type 2 diabetes (T2D) and cardiovascular disease. In this review, the molecular and cellular mechanisms involved in these undesired metabolic abnormalities induced by AAPs will be described. These mechanisms are complex, as AAPs have multiple cellular targets, significantly affecting the activities of several hormones and neuromodulators. Additionally, AAPs affect all the relevant metabolic organs, namely the liver, pancreas, adipose tissue, skeletal muscle and intestine, and the central and peripheral nervous system as well. A better undertanding of the molecular targets linking AAPs with MetS and of the mechanisms responsible for clinically different side effects of distinct AAPs is needed. This knowledge will help in the development of novel AAPs with less adverse effects as well as of adjuvant therapies to patients receiving AAPs.This article is protected by copyright. All rights reserved.

show abstract

Atypical Antipsychotics and the Human Skeletal Muscle Lipidome

Cited by 5 publications

References 79 publications

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

Atypical Antipsychotics and Metabolic Syndrome: From Molecular Mechanisms to Clinical Differences

The Antipsychotic Risperidone Alters Dihydroceramide and Ceramide Composition and Plasma Membrane Function in Leukocytes In Vitro and In Vivo

Metabolic effects of atypical antipsychotics: Molecular targets

Contact Info

Product

Resources

About