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Inhibitory effect of t 10 c 12 conjugated linoleic acid (CLA) isomer on clozapine induced adipogenesis in 3T3‐L1 cells
Author(s) -
Park Yooheon,
Kim Younghwa,
Lee Junsoo,
Park Yeonhwa
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.lb288
Subject(s) - adipogenesis , oil red o , clozapine , endocrinology , medicine , conjugated linoleic acid , fatty acid synthase , adipocyte , chemistry , lipid metabolism , linoleic acid , lipid droplet , fatty acid , biology , biochemistry , adipose tissue , schizophrenia (object oriented programming) , psychiatry
Atypical (second generation) antipsychotics such as clozapine have become the primary choice of medication for treating psychosis. An unfortunate side‐effect of these medications is weight gain, a condition often associated with the development of metabolic disorders such as diabetes. Factors thought to facilitate this weight gain include increased food intake, reduced energy expenditure, and impaired pre‐adipocyte differentiation. CLA, specifically the t 10 c 12 isomer, has been known to suppress adipogenesis both in vitro and in vivo model. Thus we tested the effect of the t 10 c 12 CLA on clozapine induced adipogenesis in 3T3‐L1 cells. 3T3‐L1 pre‐adipocytes were differentiated by the addition of insulin (1μg/ml), dexamethasone (1μM), IBMX (10mM), and 10% FBS in DMEM medium. Cells were treated with or without clozapine (10 and 20μM) and/or t 10 c 12 CLA (50μM). Lipid accumulation was measured by Oil‐red O staining and intracellular triacylglyceride contents were analyzed. mRNA level of the lipid metabolism related transcription factors were measured by RT‐PCR. Cells treated with clozapine alone showed significant increase in lipid accumulation compared to control. However, increased lipid accumulation by clozapine was significantly prevented in cells treated with CLA. mRNA level of fatty acid synthase (FAS), acetyl‐CoA carboxylase (ACC), uncoupling protein‐2 (UCP‐2), and peroxisome proliferator‐activated receptor‐γ (PPAR‐γ) in the cells treated with CLA were significantly decreased by t 10 c 12 CLA with or without treatment of clozapine. These results suggest that CLA may be used to prevent fat accumulation associated with antipsychotic administration.