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Korean Society for Biochemistry and Molecular Biology (생화학분자생물학회)
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Metformin ameliorates olanzapine-induced disturbances in POMC neuron number, axonal projection, and hypothalamic leptin resistance

  • Kim, Jaedeok (Department of Biomedical Science, Hallym University) ;
  • Lee, Nayoung (Department of Biomedical Science, Hallym University) ;
  • Suh, Sang Bum (University of Ulsan College of Medicine) ;
  • Jang, Sooyeon (Department of Biomedical Science, Hallym University) ;
  • Kim, Saeha (Department of Biomedical Science, Hallym University) ;
  • Kim, Dong-Gyu (Department of Biomedical Science, Hallym University) ;
  • Park, Jong Kook (Department of Biomedical Science, Hallym University) ;
  • Lee, Keun-Wook (Department of Biomedical Science, Hallym University) ;
  • Choi, Soo Young (Department of Biomedical Science, Hallym University) ;
  • Lee, Chan Hee (Department of Biomedical Science, Hallym University)
  • Received : 2022.02.15
  • Accepted : 2022.04.22
  • Published : 2022.06.30
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Abstract

Antipsychotics have been widely accepted as a treatment of choice for psychiatric illnesses such as schizophrenia. While atypical antipsychotics such as aripiprazole are not associated with obesity and diabetes, olanzapine is still widely used based on the anticipation that it is more effective in treating severe schizophrenia than aripiprazole, despite its metabolic side effects. To address metabolic problems, metformin is widely prescribed. Hypothalamic proopiomelanocortin (POMC) neurons have been identified as the main regulator of metabolism and energy expenditure. Although the relation between POMC neurons and metabolic disorders is well established, little is known about the effects of olanzapine and metformin on hypothalamic POMC neurons. In the present study, we investigated the effect of olanzapine and metformin on the hypothalamic POMC neurons in female mice. Olanzapine administration for 5 days significantly decreased Pomc mRNA expression, POMC neuron numbers, POMC projections, and induced leptin resistance before the onset of obesity. It was also observed that coadministration of metformin with olanzapine not only increased POMC neuron numbers and projections but also improved the leptin response of POMC neurons in the olanzapine-treated female mice. These findings suggest that olanzapine-induced hypothalamic POMC neuron abnormality and leptin resistance, which can be ameliorated by metformin administration, are the possible causes of subsequent hyperphagia.

Keywords

Acknowledgement

This research was supported by Hallym University Research Fund, 202110-005 (HRF-202110-005).

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