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Volume 23, Issue 4
  • ISSN: 1570-159X
  • E-ISSN: 1875-6190

Abstract

Background

Administration of olanzapine (OLA) is closely associated with obesity and glycolipid abnormalities in patients with schizophrenia (SCZ), although the exact molecular mechanisms remain elusive.

Objective

We conducted comprehensive animal and molecular experiments to elucidate the mechanisms underlying OLA-induced weight gain.

Methods

We investigated the mechanisms of OLA-induced adipogenesis and lipid storage by employing a real-time ATP production rate assay, glucose uptake test, and reactive oxygen species (ROS) detection in 3T3-L1 cells and AMSCs. Rodent models were treated with OLA using various intervention durations, dietary patterns (normal diets/western diets), and drug doses. We assessed body weight, epididymal and liver fat levels, and metabolic markers in both male and female mice.

Results

OLA accelerates adipogenesis by directly activating glycolysis and its downstream PI3K signaling pathway in differentiated adipocytes. OLA promotes glucose uptake in differentiated 3T3-L1 preadipocytes. In mouse models with normal glycolipid metabolism, OLA administration failed to increase food intake and weight gain despite elevated GAPDH expression, a marker related to glycolysis and PI3K-AKT. This supports the notion that glycolysis plays a significant role in OLA-induced metabolic dysfunction.

Conclusion

OLA induces glycolysis and activates the downstream PI3K-AKT signaling pathway, thereby promoting adipogenesis.

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2024-08-15
2025-03-30

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Olanzapine Induces Adipogenesis and Glucose Uptake by Activating Glycolysis and Synergizing with the PI3K-AKT Pathway
Curr. Neuropharmacol. 23, 412 (2025); https://doi.org/10.2174/1570159X22666240815120547
/content/journals/cn/10.2174/1570159X22666240815120547
/content/journals/cn/10.2174/1570159X22666240815120547
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  • Article Type:     Research Article
Keyword(s): adipocyte; glycolysis; insulin resistance; lipolysis; Olanzapine; PI3K/AKT

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