OBJECTIVES: This study aimed to elucidate the effect of bupropion (BUP) on high-fat diet (HFD)-treated rats that is to say the action of BUP on diabetes and hyperlipidemia with its consequences on liver and endothelial function. METHODS: Male Wistar rats were fed HFD or normal chow for 15 weeks then given either BUP (50 mg/kg) or distilled water by gavage for 4 weeks. The effect of BUP on diabetes, hyperlipidemia, hepatic and vascular functions as well as tumour necrosis factor-alpha (TNF)-α were assessed. The intima-media thickness of the aorta was evaluated. KEY FINDINGS: BUP significantly decreased serum lipid, liver enzyme, homeostasis model assessment for insulin resistance (HOMA-IR), serum TNF-α and the impaired glucose tolerance. Liver from rats with non-alcoholic steatohepatitis (NASH) demonstrated significant higher TNF-α level, inflammatory cell infiltration, ballooning and steatosis which significantly ameliorated by BUP treatment. Neither intima/media ratio nor vascular reactivity to acetylcholine is improved by BUP treatment. CONCLUSIONS: NASH induced by a HFD was associated with hyperlipidemia, insulin resistance, endothelial dysfunction and increase in liver TNF-α. All of these may contribute to the pathogenesis of NASH. BUP has potential role in improving metabolic and hepatic function with negative vascular effect. Since BUP is a well-known antidepressant, it will be a candidate drug in treatment of depression in hepatic diseased or metabolic disturbed patients.
OBJECTIVES: This study aimed to elucidate the effect of bupropion (BUP) on high-fat diet (HFD)-treated rats that is to say the action of BUP on diabetes and hyperlipidemia with its consequences on liver and endothelial function. METHODS: Male Wistar rats were fed HFD or normal chow for 15 weeks then given either BUP (50 mg/kg) or distilled water by gavage for 4 weeks. The effect of BUP on diabetes, hyperlipidemia, hepatic and vascular functions as well as tumour necrosis factor-alpha (TNF)-α were assessed. The intima-media thickness of the aorta was evaluated. KEY FINDINGS: BUP significantly decreased serum lipid, liver enzyme, homeostasis model assessment for insulin resistance (HOMA-IR), serum TNF-α and the impaired glucose tolerance. Liver from rats with non-alcoholic steatohepatitis (NASH) demonstrated significant higher TNF-α level, inflammatory cell infiltration, ballooning and steatosis which significantly ameliorated by BUP treatment. Neither intima/media ratio nor vascular reactivity to acetylcholine is improved by BUP treatment. CONCLUSIONS: NASH induced by a HFD was associated with hyperlipidemia, insulin resistance, endothelial dysfunction and increase in liver TNF-α. All of these may contribute to the pathogenesis of NASH. BUP has potential role in improving metabolic and hepatic function with negative vascular effect. Since BUP is a well-known antidepressant, it will be a candidate drug in treatment of depression in hepatic diseased or metabolic disturbed patients.
Authors: Stephanie W Watts; Emma S Darios; G Andres Contreras; Hannah Garver; Gregory D Fink Journal: Am J Physiol Heart Circ Physiol Date: 2021-04-30 Impact factor: 5.125