Weight gain related to treatment with atypical antipsychotics is due to activation of PKC-β.
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 pre-adipocytes and MDSCs that are brought on by protein kinase C-β (PKC-β) 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.
Pavan
C
C
Psychiatric Clinic, University of Padova, Padova, Italy.
Vindigni
V
V
Michelotto
L
L
Rimessi
A
A
Abatangelo
G
G
Cortivo
R
R
Pinton
P
P
Zavan
B
B
D017667:Adipocytes / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D050156:Adipogenesis / Q000187:drug effects* / Q000235:genetics; D000818:Animals; D000831:Animals, Newborn; D014150:Antipsychotic Agents / Q000009:adverse effects*; D018929:Cell Culture Techniques; D002454:Cell Differentiation / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D002478:Cells, Cultured; D004789:Enzyme Activation; D015870:Gene Expression / Q000187:drug effects; D020868:Gene Silencing / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism*; D064546:Protein Kinase C beta; D034741:RNA, Small Interfering / Q000235:genetics / Q000494:pharmacology; D051381:Rats; D013234:Stem Cells / Q000166:cytology / Q000187:drug effects* / Q000201:enzymology; D015430:Weight Gain / Q000187:drug effects* / Q000235:genetics
D014150:Antipsychotic Agents; D034741:RNA, Small Interfering; D011493:Protein Kinase C; D064546:Protein Kinase C beta