TY  - JOUR
AU  - Yi, Weijie
AU  - Lian, Jiamei
AU  - Deng, Chao
PY  - 2026
DA  - 2026/07/09
TI  - The Effect and Mechanisms of Risperidone and Voluntary Exercise Intervention on Hepatic Lipid Metabolism in Juvenile Female Rats
JO  - Recent Progress in Nutrition
SP  - 013
VL  - 06
IS  - 03
AB  - Risperidone is a commonly used antipsychotic drug in juveniles, but with serious metabolic side-effects. Previous evidence suggests that exercise mitigates risperidone-induced hypertriglyceridemia and adipose accumulation, yet the underlying hepatic mechanisms remain unclear. In this study, female juvenile rats were randomly assigned to four groups (n = 8/group): Vehicle + Sedentary, Risperidone (0.9 mg/kg, twice daily) + Sedentary, Vehicle + Exercise (3-hour voluntary access to a running wheel/day), and Risperidone + Exercise groups (n = 8/group). Following 4-week treatment, liver tissue was harvested for subsequent analyses. Risperidone increased hepatic expression of fatty acid synthase (FAS) and upstream stimulatory factor 1 (USF1), while exercise attenuated these changes and elevated the pAMPK/AMPK ratio, indicating suppressed lipogenesis. Risperidone also upregulated peroxisome proliferator-activated receptor γ (PPARγ) and CD36, promoting lipid uptake and storage; these effects were reversed by exercise, which additionally reduced FSP27 expression. Furthermore, exercise enhanced lipolytic and β-oxidative capacity, as evidenced by increased adipose triglyceride lipase (ATGL), hormone-sensitive lipase (HSL), and restoration of peroxisome proliferator-activated receptor γ coactivator 1α (PGC1α) levels suppressed by risperidone. Collectively, risperidone promotes hepatic lipid accumulation by stimulating USF1/FAS-mediated lipogenesis and PPARγ/CD36-driven uptake while suppressing the PGC1α signaling pathway associated with β-oxidation. Voluntary exercise counteracts these alterations, thereby ameliorating risperidone-induced hepatic lipid dysregulation.
SN  - 2771-9871
UR  - https://doi.org/10.21926/rpn.2603013
DO  - 10.21926/rpn.2603013
ID  - Yi2026
ER  -