Depressive disorders are frequently managed with long-term use of antidepressant medication. Fluoxetine (FLX) is the first selective serotonin reuptake inhibitor to be widely available for the treatment of depression. The present study focuses on the effects and mechanisms of the lipid metabolism abnormalities caused by FLX in patients and in a mouse model of depression. Depression severity was assessed by the Hamilton Depression Scale (HAMD). Triglyceride (TG), cholesterol (TC) and low-density lipoprotein (LDL) serum levels were assessed in 28 patients with depression, aged 31.2±3.3 years, treated with FLX (20 to 60 mg/day) for 8 weeks. Meanwhile, the serum levels of other lipid metabolism-related parameters, such as high-density lipoprotein (HDL), apolipoprotein A1 (APOA1) and apolipoprotein B (ApoB), were also determined. The infiuence of FLX on the hepatic lipid profile and hepatic gene expression of both lipogenic and lipolytic enzymes was evaluated in a mouse model of depression treated with FLX (10 mg·kg^-1·d^-1, ip) for 4 weeks. We showed that the serum TG, TC and LDL levels were significantly increased in patients with depression after FLX treatment. The elevation in serum TG levels in the patients was not affected by gender or family history. FLX treatment did not significantly alter serum HDL, APOA1 or APOB levels in the patients. We further demonstrated in mice with depression that FLX treatment increased the hepatic TG level by increasing the expression of lipogenic enzymes and decreasing the expression of lipolytic enzymes in the liver. Antidepressive therapy with FLX is associated with lipid metabolism abnormalities, which are in part mediated by disturbances in hepatic lipid metabolism homeostasis. The findings contribute to the uncovering of metabolic adverse reactions in the pharmacological therapy of depression.

中文翻译：

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氟西汀通过作用于抑郁症患者和小鼠的肝脏，诱导脂质代谢异常。

长期使用抗抑郁药可以治疗抑郁症。氟西汀（FLX）是第一种选择性5-羟色胺再摄取抑制剂，可广泛用于治疗抑郁症。本研究的重点是在患者和抑郁症小鼠模型中，由FLX引起的脂质代谢异常的作用和机制。抑郁严重程度通过汉密尔顿抑郁量表（HAMD）进行评估。对28例31.2±3.3岁抑郁症患者进行了甘油三酯（TG），胆固醇（TC）和低密度脂蛋白（LDL）血清水平评估，这些患者接受了FLX（20至60 mg /天）治疗8周。同时，还测定了血清中其他与脂代谢相关的参数，例如高密度脂蛋白（HDL），载脂蛋白A1（APOA1）和载脂蛋白B（ApoB）。^-1 ·d ^-1，ip）4周。我们显示，FLX治疗后抑郁症患者的血清TG，TC和LDL水平显着增加。患者的血清TG水平升高不受性别或家族史的影响。FLX治疗并未显着改变患者的血清HDL，APOA1或APOB水平。我们在患有抑郁症的小鼠中进一步证明，FLX治疗可通过增加脂肪形成酶的表达并降低肝脏中脂解酶的表达来提高肝脏TG的水平。用FLX进行的抗抑郁治疗与脂质代谢异常有关，脂质代谢异常部分是由肝脏脂质代谢体内稳态的紊乱介导的。这些发现有助于发现抑郁症的药物不良反应中的代谢不良反应。