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

Publisher: Nature Publishing Group Specialist Journals Country of Publication: England NLM ID: 9607835 Publication Model: Print-Electronic Cited Medium: Print ISSN: 1359-4184 (Print) Linking ISSN: 13594184 NLM ISO Abbreviation: Mol Psychiatry Subsets: MEDLINE

Publication: 2000- : Houndmills, Basingstoke, UK : Nature Publishing Group Specialist Journals
Original Publication: Houndmills, Hampshire, UK ; New York, NY : Stockton Press, c1996-

Adipocytes/*drug effects ; Antipsychotic Agents/*pharmacology ; Lipid Metabolism/*drug effects ; Weight Gain/*drug effects; Adipocytes/cytology ; Adipocytes/metabolism ; Animals ; Benzodiazepines/pharmacology ; Cell Size/drug effects ; Drug Administration Schedule ; Fatty Acid Synthases/drug effects ; Fatty Acid Synthases/genetics ; Fatty Acid Synthases/metabolism ; Gene Expression Regulation/drug effects ; Glucose Transport Proteins, Facilitative/drug effects ; Glucose Transport Proteins, Facilitative/genetics ; Glucose Transport Proteins, Facilitative/metabolism ; Haloperidol/pharmacology ; Male ; Obesity/chemically induced ; Obesity/metabolism ; Olanzapine ; Piperazines/pharmacology ; RNA/analysis ; Rats ; Rats, Sprague-Dawley ; Statistics, Nonparametric ; Sterol Esterase/drug effects ; Sterol Esterase/genetics ; Sterol Esterase/metabolism ; Thiazoles/pharmacology

Although antipsychotics are established drugs in schizophrenia treatment, they are admittedly known to induce side effects favoring the onset of obesity and worsening its complications. Despite potential involvement of histamine receptor antagonism, or of other neurotransmitter systems, the mechanism by which antipsychotic drugs increase body weight is not elucidated. The aim of the present study was to investigate whether chronic antipsychotic treatments can directly alter the regulation of two main functions of white adipose tissue: lipolysis and glucose utilization. The influence of a classical antipsychotic (haloperidol) was compared to that of two atypical antipsychotics, one known to favor weight gain (olanzapine), the other not (ziprasidone). Cell size, lipolytic capacity and glucose transport activity were determined in white adipocytes of rats subjected to 5-week oral treatment with these antipsychotics. Gene expression of adipocyte proteins involved in glucose transport or fat storage and mobilization, such as glucose transporters (GLUT1 and GLUT4), leptin, matrix metallo-proteinase-9 (MMP9), hormone-sensitive lipase (HSL) and fatty acid synthase (FAS) was also evaluated. Adipocytes from chronic olanzapine-treated rats exhibited decreased lipolytic activity, lowered HSL expression and increased FAS expression. These changes were concomitant to enlarged fat deposition and adipocyte size. Alterations were observed in adipocytes from olanzapine-treated rats whereas the other antipsychotics did not induce any notable disorder. Our results therefore show evidence of an effect of chronic antipsychotic treatment on rat adipocyte metabolism. Thus, impairment of fat cell lipolysis should be considered as a side effect of certain antipsychotics, leading, along with the already documented hyperphagia, to the excessive weight gain observed in patients under prolonged treatment..

0 (Antipsychotic Agents)
0 (Glucose Transport Proteins, Facilitative)
0 (Piperazines)
0 (Thiazoles)
12794-10-4 (Benzodiazepines)
63231-63-0 (RNA)
6UKA5VEJ6X (ziprasidone)
EC 2.3.1.85 (Fatty Acid Synthases)
EC 3.1.1.13 (Sterol Esterase)
J6292F8L3D (Haloperidol)
N7U69T4SZR (Olanzapine)

Date Created: 20070111 Date Completed: 20070807 Latest Revision: 20220318

20250114

10.1038/sj.mp.4001948

17211438