Vitamin D deficiency exacerbates atypical antipsychotic-induced metabolic side effects in rats: Involvement of the INSIG/SREBP pathway

Dang, Ruili; Jiang, Pei; Cai, Hualin; Huan-de, LI; Guo, Ren; Wu, Yanqin; Zhang, Lihong; Zhu, Wenye; He, Xin; Liu, Yiping; Xu, Ping

doi:10.1016/j.euroneuro.2015.04.028

Cited by 29 publications

(29 citation statements)

References 36 publications

(44 reference statements)

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“…An experimental study showed that this metabolic alteration can be aggravated by VDD while it can be alleviated by vitamin D supplementation (38). The observed insignificantly lower level of vitamin D in patients on atypical antipsychotics compared with patients on typical antipsychotics indicates that there seems to be no differential effect of the type of antipsychotics on the plasma level of vitamin D. Our observation, however, needs a confirmation through a large population study as the small sample size used for this study was a major limitation.…”

Section: Discussionmentioning

confidence: 99%

Vitamin D Levels in Different Severity Groups of Schizophrenia

et al. 2017

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BackgroundVitamin D deficiency (VDD) continues to be associated with schizophrenia, but there is the dearth of information on the relationship between the severity of schizophrenia and plasma levels of vitamin D. This study, therefore, determined the plasma levels of vitamin D in different severity groups of schizophrenia.Materials and methodsPlasma level of vitamin D was determined in 60 patients with schizophrenia and 30 apparently healthy individuals who served as controls. Patients with schizophrenia were classified into mildly ill, moderately ill, markedly ill, and severely ill groups using the Positive and Negative Syndrome Scale (PANSS).ResultsThe mean level of vitamin D was significantly lower in patients with schizophrenia compared with the controls. Similarly, there was a significant association between VDD and schizophrenia. The mean plasma levels of vitamin D were not significantly different when the mildly, moderately, markedly, and severely ill groups were compared with one another and there was no significant correlation between vitamin D level and PANSS scores. Furthermore, patients on atypical antipsychotics had an insignificantly lower level of vitamin D compared with the patients on typical antipsychotics.ConclusionIt could be concluded from this study that patients with schizophrenia have low plasma vitamin D level which does not appear to be associated with the severity of schizophrenia and type of antipsychotics. Therefore, regular screening for vitamin D status of patients with schizophrenia is suggested in order to allow for the institution of appropriate clinical intervention when necessary.

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Section: Discussionmentioning

confidence: 99%

Vitamin D Levels in Different Severity Groups of Schizophrenia

et al. 2017

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“…While the mechanisms underlying these associations are still not clear, the research literature suggests that vitamin D deficiency could: 1) Initiate the cholesterol de novo synthesis through the activation of the sterol regulatory element binding protein 2 (SREBP2) [23]; 2) Accelerate foam cell formation through the c-Jun N-terminal kinase pathway, a process that eventually leads to atherosclerosis [24]; 3) Reduce the blunting effect of the endoplasmic reticulum (ER) products of insulin-induced gene-2 (Insig-2) on SREBP2 [25] (The Insig-2 prohibits the translocation of SREBP-2 to the nucleus, and inhibits cholesterol biosynthesis); 4) Induce insulin resistance by upregulating the peroxisome proliferated-activated receptor-gamma (PPAR-g) expression, which causes impaired b-cell proliferation [26]. In contrast, 125 (OH) 2 D 3 supplementation has been implied to be protective against cardiometabolic diseases by reducing macrophage cholesterol uptake [24], suppressing foam cell formation [25], and attenuating insulin resistance [26].…”

Section: Possible Mechanisms Underlying Vitamin D Deficiencymentioning

confidence: 99%

Associations of vitamin D status with markers of metabolic health: A community-based study in Shanghai, China

Zhu

Heil

2018

Diabetes & Metabolic Syndrome: Clinical Research & Revi

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“…Previous evidence has shown that the abnormal lipid and cholesterol synthesis causedby CLZ or OLZ were associated with up-regulation of hepatic sterol regulatory element-binding proteins (SREBPs, including SREBP-1c and SREBP-2) and their associated target genes 25–29 . Notably, the expression of hepatic lipogenic genes was enhanced in insulin resistance 27, 30 , however the underlying mechanism was unclear. The carbohydrate response element binding protein (ChREBP) was a key player in the induction of genes of de novo fatty acid synthesis (lipogenesis) in response to glucose.…”

Section: Introductionmentioning

confidence: 99%

Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats

Liu

Lian

et al. 2017

Sci Rep

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Chronic treatment with second-generation antipsychotic drugs (SGAs) has been associated with an increased risk of metabolic syndrome. To evaluate the longitudinal changes in glucose-lipid homeostasis after SGA use, we studied the time-dependent effects of olanzapine (OLZ) (3 mg/kg, b.i.d.) or clozapine (CLZ) (20 mg/kg, b.i.d.) treatment on metabolic profiles for 9 weeks in rats. Although only OLZ significantly increased body weight in rats, both OLZ and CLZ elevated blood lipid levels. Chronic OLZ treatment induced significant weight gain leading to a higher fasting insulin level and impaired glucose tolerance, whereas CLZ lowered fasting insulin levels and impaired glucose tolerance independent of weight gain. Treatment with both drugs deranged AKT/GSK phosphorylation and up-regulated muscarinic M3 receptors in the rats’ livers. Consistent with an elevation in lipid levels, both OLZ and CLZ significantly increased the protein levels of nuclear sterol regulatory element-binding proteins (SREBPs) in the liver, which was associated with improvement in hepatic histamine H1R. However, enhanced carbohydrate response element binding protein (ChREBP) signalling was observed in only CLZ-treated rats. These results suggest that SGA-induced glucose-lipid metabolic disturbances could be independent of weight gain, possibly through activation of SREBP/ChREBP in the liver.

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Vitamin D deficiency exacerbates atypical antipsychotic-induced metabolic side effects in rats: Involvement of the INSIG/SREBP pathway

Cited by 29 publications

References 36 publications

Vitamin D Levels in Different Severity Groups of Schizophrenia

Vitamin D Levels in Different Severity Groups of Schizophrenia

Associations of vitamin D status with markers of metabolic health: A community-based study in Shanghai, China

Time-dependent changes and potential mechanisms of glucose-lipid metabolic disorders associated with chronic clozapine or olanzapine treatment in rats

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