Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment

Minet-Ringuet, Julie; Even, Patrick C.; Valet, Philippe; Carpéné, Christian; Visentin, Virgile; Prévot, Danielle; Daviaud, Danièle; Quignard‐Boulangé, Annie; Tomé, Daniel; Beaurepaire, Renaud de

doi:10.1038/sj.mp.4001948

Cited by 90 publications

(78 citation statements)

References 41 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Lipolytic activity was assessed by the glycerol released by fat cells into the medium after a 90-min incubation in 400 μl final volume with the tested agents, as previously described (19). Results were expressed as μmoles of glycerol released / 100 mg cellular lipids / 90 min, or as the percentage of 5 nM isoprenaline-induced stimulation.…”

Section: Chemicalsmentioning

confidence: 99%

Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes

2009

View full text Add to dashboard Cite

Visfatin, a protein identified as a secretion product of visceral fat in humans and mice, is also expressed in different anatomical locations, and is known as pre-B cell-colony enhancing factor (PEBF1). It is also an enzyme displaying nicotinamide phosphoribosyltransferase activity (Nampt). The evidence that levels of visfatin correlate with visceral fat mass has been largely debated and widely extended to other regulations in numerous clinical studies and in diverse animal models. On the opposite, the initial findings regarding the capacity of visfatin/Nampt/PEBF1 to bind and to activate the insulin receptor have been scarcely reproduced, and even were contradicted in recent reports. Since the putative insulin mimicking effects of visfatin/Nampt/PEBF1 have never been tested on mature human adipocytes, at least to our knowledge, we tested different human visfatin batches on human fat cells freshly isolated from subcutaneous abdominal fat and exhibiting high insulin responsiveness. Up to 10 nM, visfatin was devoid of clear activatory action on glucose transport in human fat cells while, in the same conditions, insulin increased by more than threefold the basal 2-deoxyglucose uptake. Moreover, visfatin was unable to mimic the lipolysis inhibition induced by insulin. Visfatin definitively cannot be considered as a direct activator of insulin signalling in human fat cells. Nevertheless itsin vivo effects on insulin release and on glucose handling deserve to further study the role of this multifunctional extracellular enzyme in obese and diabetic states.

show abstract

Section: Chemicalsmentioning

confidence: 99%

Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes

2009

View full text Add to dashboard Cite

show abstract

“…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. 13 In light of these considerations, it could be concluded that obesity event associated with administration of different APDs could be enhanced by several pathways. To our knowledge, no study has been performed to test different classes of atypical neuroleptics on human adipocytes.…”

Section: Introductionmentioning

confidence: 99%

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

et al. 2009

View full text Add to dashboard Cite

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.

show abstract

“…Page 4 of 34 A c c e p t e d M a n u s c r i p t 4 drugs altered lipogenesis and lipolysis in favor of progressive lipid accumulation and adipocyte enlargement (Vestri et al, 2007;Minet-Ringuet et al, 2007). Studies on glucose transport into isolated rat epitrochlearis skeletal muscle did not evidence any effect of clozapine (Houseknecht et al, 2007).…”

Section: Introductionmentioning

confidence: 99%

Effects of olanzapine on glucose transport, proliferation and survival in C2C12 myoblasts

Tulipano

Spano

2008

Molecular and Cellular Endocrinology

View full text Add to dashboard Cite

Please cite this article as: Tulipano, G., Spano, P.F., Cocchi, D., Effects of olanzapine on glucose transport, proliferation and survival in C2C12 myoblasts, Molecular and Cellular Endocrinology (2007), doi:10.1016/j.mce.2008 This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. ABSTRACTThe aim of our study was to investigate the direct effects of atypical antipsychotics on muscle cell functions in order to ascertain the diabetic liability of these drugs. We investigated the effects of olanzapine, clozapine and -methyl-5-hydroxytryptamine on basal glucose uptake and glucose uptake in response to insulin using in vitro cultures of mouse skeletal muscle satellite cells (C2C12). We extended our study to the effects of these compounds on cell proliferation, survival and differentiation into myotubes and on the growth of differentiated myotubes. Olanzapine and -methyl-5-HT stimulated 2-deoxyglucose uptake in C2C12 myoblasts in a dose-dependent manner (minimal effective dose: 2 µM olanzapine and 10 µM -methyl-5-HT). The treatment with clozapine had no effect on glucose transport. Insulin and olanzapine increased the plasma membrane abundance of glucose transporter GLUT4. We investigated whether protein kinase Akt (PKB) and AMP-dependent kinase may partecipate in mediating olanzapine effects on glucose transport. Clozapine and olanzapine did not induce DNA laddering in differentiating myoblasts and differentiated myotubes and did not affect myotube growth. Olanzapine-induced glucose disposal in vitro is consistent with the acute lowering of plasma glucose/insulin concentrations that occurs in rats before olanzapine-induced overeating (Albaugh et al., 2006).

show abstract

Alterations of lipid metabolism and gene expression in rat adipocytes during chronic olanzapine treatment

Cited by 90 publications

References 41 publications

Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes

Lack of direct insulin-like action of visfatin/Nampt/PBEF1 in human adipocytes

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

Effects of olanzapine on glucose transport, proliferation and survival in C2C12 myoblasts

Contact Info

Product

Resources

About