Selegiline ameliorated dyslipidemia and hepatic steatosis in high-fat diet mice

Tian, Zhen; Wang, Xinyue; Han, Tianshu; Sun, Chengbo

doi:10.1016/j.intimp.2023.109901

Cited by 8 publications

(5 citation statements)

References 46 publications

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“…Other studies concerning the effect of a selective/non-selective MAOinhibitor have shown that MAO inhibitors repress adipogenesis in hBM-MSCs [18,25]. Also, selegiline improved lipid metabolism in the liver of HFD-fed mice due to regulating fatty acid oxidation [20]. Another MAO inhibitor, phenelzine, has been reported to improve obesity-related complications [26].…”

Section: Discussionmentioning

confidence: 97%

“…Pargyline, a monoamine oxidase inhibitor administered at a dosage of 30 mg/kg, promoted lipolysis and increased the levels of free fatty acids in rats [19]. A recent study reported that selegiline demonstrated a protective effect against HFD-induced dyslipidemia and hepatic steatosis [20]. Despite the established metabolic benefits of selegiline in obese rodents, the specific mechanisms behind MAOB inhibition and lipid metabolism remain unclear.…”

Section: Introductionmentioning

confidence: 99%

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Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice

Joung,

Oh,

Song

et al. 2023

Pharmaceutics

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Obesity, as a major cause of many chronic diseases such as diabetes, cardiovascular disease, and cancer, is among the most serious health problems. Increased monoamine oxidase (MAO) activity has been observed in the adipose tissue of obese humans and animals. Although previous studies have already demonstrated the potential of MAO-B inhibitors as a treatment for this condition, the mechanism of their effect has been insufficiently elucidated. In this study, we investigated the anti-obesity effect of selegiline, a selective MAO-B inhibitor, using in vivo animal models. The effect was evaluated through an assessment of body energy homeostasis, glucose tolerance tests, and biochemical analysis. Pharmacological inhibition of MAO-B by selegiline was observed to reduce body weight and fat accumulation, and improved glucose metabolism without a corresponding change in food intake, in HFD-fed obese mice. We also observed that both the expression of adipogenenic markers, including C/EBPα and FABP4, and lipogenic markers such as pACC were significantly reduced in epididymal white adipose tissues (eWATs). Conversely, increased expression of lipolytic markers such as ATGL and pHSL and AMPK phosphorylation were noted. Treating obese mice with selegiline significantly increased expression levels of UCP1 and promoted eWAT browning, indicating increased energy expenditure. These results suggest that selegiline, by inhibiting MAO-B activity, is a potential anti-obesity treatment.

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Section: Discussionmentioning

confidence: 97%

Section: Introductionmentioning

confidence: 99%

Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice

Joung,

Oh,

Song

et al. 2023

Pharmaceutics

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“…Previous studies have shown that selegiline is highly effective in reducing inflammatory parameters and oxidative stress caused by free radicals (Ahmed & Chetia, 2023). Furthermore, SEL has been shown to reduce levels of reactive oxygen species and malondialdehyde and increase superoxide dismutase activity in the liver of mice exposed to a high‐fat diet and physical activity (Tian et al., 2023). In a study, it has been reported that there is a negative correlation between oxidative stress factors and cognitive memory (S. Ghaderi et al., 2024).…”

Section: Discussionmentioning

confidence: 99%

Protective effects of selegiline against amyloid beta‐induced anxiety‐like behavior and memory impairment

Mohamadpour,

Mirazi,

Komaki

et al. 2024

Brain and Behavior

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BackgroundAlzheimer's disease (AD) is a complex and common neurodegenerative disorder. The present study aimed to investigate the potential effects of selegiline (SEL) on various aspects of memory performance, anxiety, and oxidative stress in an AD rat model induced by intracerebroventricular injection of amyloid beta1‐42 (Aβ1‐42).MethodsOral administration of SEL at a dose of 0.5 mg/kg/day was performed for 30 consecutive days. Following the 30 days, several tests, including the open‐field, elevated plus‐maze, novel object recognition, Morris water maze, and passive avoidance learning were conducted to assess locomotor activity, anxiety‐like behavior, recognition memory, spatial memory, and passive avoidance memory, respectively.ResultsThe results indicate that the induction of AD in rats led to recognition memory, spatial memory, and passive avoidance memory impairments, as well as increased anxiety. Additionally, the AD rats exhibited a decrease in total antioxidant capacity and an increase in total oxidant status levels, suggesting an imbalance in oxidative‐antioxidant status. However, the administration of SEL improved memory performance, reduced anxiety, and modulated oxidative‐antioxidant status in AD rats.ConclusionsThese findings provide evidence that SEL may alleviate anxiety‐like behavior and cognitive deficits induced by Aβ through modulation of oxidative‐antioxidant status.

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“…Selegiline (previously called L-deprenyl) is a clinically widely used, irreversible and selective inhibitor of MAOB, which is primarily used to treat Parkinson's disease and depression [28,29]. We and others have reported that selegiline significantly decreased fatty liver in rodent animals fed with a lipid-rich diet [16,17,30]. Only one recent study revealed that selegiline reduced atherosclerosis by inhibiting ROS production, plasma LDL-C levels, the expression of adhesion molecules and proinflammatory cytokines [16].…”

Section: Discussionmentioning

confidence: 99%

“…after a 10-week exposure to ND or HFD feeding. The dose of selegiline was selected based upon one previous report [17], and the calculation from a simple practice guide for dose conversion between mice and human [18]. The oral dose of selegiline used in the human therapy is 5-10 mg/day [19].…”

Section: Animalsmentioning

confidence: 99%

Inhibition of MAOB Ameliorated High-Fat-Diet-Induced Atherosclerosis by Inhibiting Endothelial Dysfunction and Modulating Gut Microbiota

Tian,

Wang,

Han

et al. 2023

Nutrients

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In this study, monoamine oxidase B (MAOB) was activated under pathological conditions, and was the novel source of cardiovascular reactive oxygen species (ROS). ROS-induced endothelial dysfunction results in sustained and chronic vascular inflammation, which is central to atherosclerotic diseases. However, whether MAOB regulates endothelial oxidative stress and its related mechanism and whether gut microbiota mediates the anti-atherosclerosis effect of MAOB inhibitor remains unclear. In our study, MAOB expressions were elevated in high-fat diet (HFD) fed mice aortas, but only in vascular endothelial cells (not in smooth muscle cells). MAOB small interfering RNA significantly attenuated the palmitic-acid (PA)-induced endothelial oxidative stress and dysfunction. Furthermore, RNA-sequencing data revealed that MAOB knockdown decreased the levels of proinflammatory and apoptotic gene induced by PA. Microarray analysis and qPCR assay showed that miR-3620-5p was significantly decreased under the HFD condition. The dual-luciferase reporter, Western blot and qPCR assay confirmed that miR-3620-5p directly regulated MAOB by binding to its mRNA 3′UTR. Moreover, inhibition of MAOB by selegiline significantly ameliorated endothelial dysfunction and reduced atherosclerotic burden in HFD-fed ApoE−/− mice. Finally, 16S rRNA sequencing showed that selegiline significantly altered the community compositional structure of gut microbiota. Specifically, selegiline treatment enriched the abundance of Faecalibaculum and Akkermansia, decreased the abundance of unclassified_f__Lachnospiraceae, Desulfovibrio, and Blautia, and these genera were significantly correlated with the serum biochemical indices. Taken together, our findings showed that MAOB controlled endothelial oxidative stress homeostasis, and revealed the anti-atherosclerotic effect of selegiline by ameliorating endothelial dysfunction and modulating the composition and function of gut microbiota.

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Selegiline ameliorated dyslipidemia and hepatic steatosis in high-fat diet mice

Cited by 8 publications

References 46 publications

Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice

Selegiline Modulates Lipid Metabolism by Activating AMPK Pathways of Epididymal White Adipose Tissues in HFD-Fed Obese Mice

Protective effects of selegiline against amyloid beta‐induced anxiety‐like behavior and memory impairment

Inhibition of MAOB Ameliorated High-Fat-Diet-Induced Atherosclerosis by Inhibiting Endothelial Dysfunction and Modulating Gut Microbiota

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