Clozapine enhances differentiation of adipocyte progenitor cells

Hemmrich, Karsten; Gummersbach, C.; Pallua, Norbert; Luckhaus, Christian; Fehsel, Karin

doi:10.1038/sj.mp.4001892

Cited by 30 publications

(21 citation statements)

References 12 publications

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“…Thus, increases in fat mass may represent a sex-independent effect of AAPs that occurs regardless of changes in food intake. This is supported by in vitro studies in adipocytes, which have reliably shown AAP-associated increases in lipogenesis, anti-lipolysis (Albaugh et al 2011;Minet-Ringuet et al 2007;Vestri et al 2007), and pre-adipocyte differentiation (Hemmrich et al 2006;Yang et al 2007). This may be clinically relevant given that both psychotic illness and AAP treatment have been associated with visceral fat distribution (Cuerda et al 2011;xGilles et al 2010;Joseph et al 2011;Zhang et al 2004), which emerges as a strong and independent predictor of cardiovascular disease and related morbidities (Boyko et al 2000;Kramer et al 2009;Kuk et al 2006).…”

Section: Discussion/conclusionmentioning

confidence: 90%

Atypical antipsychotics and effects on feeding: from mice to men

et al. 2016

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The findings from this review indicate that the varying levels of AAP-related weight gain reflect changes in both appetite and feeding behaviors, which differ by type of AAP. However, inconsistencies exist among the studies (both human and rodent) that may reflect considerable differences in study design and methodology. Future studies examining underlying mechanisms of antipsychotic-induced weight gain are recommended in order to develop strategies addressing the serious metabolic side effect of AAPs.

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Section: Discussion/conclusionmentioning

confidence: 90%

Atypical antipsychotics and effects on feeding: from mice to men

et al. 2016

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“…Previous studies have suggested that enhanced adipogenesis during preadipocyte differentiation is a potential mechanism of weight gain associated with the second generation antipsychotic medications (Yang et al, 2007;Hemmrich et al, 2006;Yang et al, 2009;Vestri et al, 2007) This study examined the effect of berberine, a botanic alkaloid on adipogenesis induced by clozapine and risperidone. The results show that both 15 μm and 30 μm clozapine signifi cantly increased adipogenesis in 3T3L-1 cells.…”

Section: Discussionmentioning

confidence: 99%

“…These include these medications lowering the resting energy expenditure (REE) (Sharpe et al, 2005), causing an increased food intake (Gothelf et al, 2002), interactions of drugs with the histamine receptor (Kroeze et al, 2003) and the serotonin receptor 2C (Malhotra, 2004) and increased peripheral adipogenesis during preadipocyte differentiation (Yang et al, 2007). Several research groups have reported that clozapine induces differentiation of preadipocytes (Hemmrich et al, 2006;Yang et al, 2009;Vestri et al, 2007) and more recent studies have suggested that increased expression levels of the sterol regulatory element binding protein-1 (SREBP-1) ) and its related proteins could be a potential mechanism for antipsychotic induced weight gain. Additionally, risperidone treatment has been reported to increase the rate of lipogenesis in primary cultured rat adipocytes (Vestri et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Berberine inhibits SREBP‐1‐related clozapine and risperidone induced adipogenesis in 3T3‐L1 cells

Kutscher

Davies

2010

Phytotherapy Research

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Weight gain is a common and potentially serious complication associated with the treatment of second generation antipsychotics such as clozapine and risperidone. Increased peripheral adipogenesis via the SREBP-1 pathway could be one critical mechanism responsible for antipsychotic drug-induced weight gain. Berberine, a botanical alkaloid, has been shown in our previous studies to inhibit adipogenesis in cell and animal models. MTT was used to determine the cytotoxic effects of clozapine and risperidone in combination with berberine. Differentiation of 3T3-L1 cells was monitored by Oil-Red-O staining and the expression of SREBP-1 and related proteins was determined by real-time RT-PCR and western blotting. The results showed that neither clozapine nor risperidone, alone or in combination with berberine had significant effects on cell viability. Eight days treatment with 15 μM clozapine increased adipogenesis by 37.4% and 50 μM risperidone increased adipogenesis by 26.5% during 3T3-L1 cell differentiation accompanied by increased SREBP-1, PPARγ, C/EBPα, LDLR and Adiponectin gene expression. More importantly, the addition of 8 μM berberine diminished the induction of adipogenesis almost completely accompanied by down-regulated mRNA and protein expression levels of SREBP-1-related proteins. These encouraging results may lead to the use of berberine as an adjuvant to prevent weight gain during second generation antipsychotic medication.

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“…Clozapine was shown to enhance differentiation of adipose tissue precursor cells to mature adipocytes. 11 Similarly, olanzapine induced adipogenesis in 3T3-L1 preadipocytes, probably through activation of the sterol regulatory element-binding protein-1 regulatory pathway. 12 A recent study, in which olanzapine, ziprasidone and haloperidol were tested on animal adipocytes, showed that only olanzapine administration decreased lipolysis in adipocytes, as well as induced a gene fatty acid synthase overexpression and a gene hormonesensitive lipase repression that resulted in a significant fat accumulation in rats.…”

Section: Introductionmentioning

confidence: 98%

Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-β

et al. 2009

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Atypical antipsychotics (APDs) are currently used in clinical practice for a variety of mental disorders such as schizophrenia, bipolar disorder and severe behavioral disturbances. A well-known disadvantage of using these compounds is a propensity for weight gain, resulting frequently in obesity. The mechanisms underlying pharmacologically induced weight gain are still controversial. The objective of this study was to evaluate in vitro the effects of different APDs on adipogenic events in cultured human pre-adipocytes and in rat muscle-derived stem cells (MDSCs), aiming to identify a common intracellular event contributable to these drugs. Culture behavior was evaluated in terms of cell proliferation, lipid accumulation, gene expression and morphological features. Results indicate that APDs influence adipogenic events through changes in the differentiation and proliferation of preadipocytes and MDSCs that are brought on by protein kinase C-b (PKC-b) activation. These data identify a signaling route that could be a potential target of pharmacological approaches for preventing the weight gain associated with APD treatment.

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Clozapine enhances differentiation of adipocyte progenitor cells

Cited by 30 publications

References 12 publications

Atypical antipsychotics and effects on feeding: from mice to men

Atypical antipsychotics and effects on feeding: from mice to men

Berberine inhibits SREBP‐1‐related clozapine and risperidone induced adipogenesis in 3T3‐L1 cells

Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-β

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