Acyl coenzyme A binding protein (ACBP), also known as diazepam binding inhibitor (DBI) is a multifunctional protein with an intracellular action (as ACBP), as well as with an extracellular role (as DBI). The plasma levels of soluble ACBP/DBI are elevated in human obesity and reduced in anorexia nervosa. Accumulating evidence indicates that genetic or antibody-mediated neutralization of ACBP/DBI has anorexigenic effects, thus inhibiting food intake and inducing lipo-catabolic reactions in mice. A number of anorexiants have been withdrawn from clinical development because of their side effects including an increase in depression and suicide. For this reason, we investigated the psychiatric impact of ACBP/DBI in mouse models and patient cohorts. Intravenously (i.v.) injected ACBP/DBI protein conserved its orexigenic function when the protein was mutated to abolish acyl coenzyme A binding, but lost its appetite-stimulatory effect in mice bearing a mutation in the γ2 subunit of the γ-aminobutyric acid (GABA) A receptor (GABA_AR). ACBP/DBI neutralization by intraperitoneal (i.p.) injection of a specific mAb blunted excessive food intake in starved and leptin-deficient mice, but not in ghrelin-treated animals. Neither i.v. nor i.p. injected anti-ACBP/DBI antibody affected the behavior of mice in the dark–light box and open-field test. In contrast, ACBP/DBI increased immobility in the forced swim test, while anti-ACBP/DBI antibody counteracted this sign of depression. In patients diagnosed with therapy-resistant bipolar disorder or schizophrenia, ACBP/DBI similarly correlated with body mass index (BMI), not with the psychiatric diagnosis. Patients with high levels of ACBP/DBI were at risk of dyslipidemia and this effect was independent from BMI, as indicated by multivariate analysis. In summary, it appears that ACBP/DBI neutralization has no negative impact on mood and that human depression is not associated with alterations in ACBP/DBI concentrations.

酰基辅酶A结合蛋白（ACBP），也称为地西epa结合抑制剂（DBI），是一种具有细胞内作用（如ACBP）和细胞外作用（如DBI）的多功能蛋白。可溶性ACBP / DBI的血浆水平在人类肥胖症中升高，在神经性厌食症中降低。越来越多的证据表明，遗传或抗体介导的ACBP / DBI中和具有厌食作用，从而抑制了食物的摄入并诱发了小鼠的脂质-分解代谢反应。由于其副作用包括抑郁症和自杀增加，许多厌食症已从临床研究中撤出。因此，我们调查了ACBP / DBI在小鼠模型和患者队列中对精神病的影响。静脉注射（iv_一种R）。通过腹膜内（ip）注射特定mAb来中和ACBP / DBI，会使饥饿和瘦素缺乏的小鼠的食物摄入过多，但生长素释放肽治疗的动物却没有。静脉和腹腔注射的抗ACBP / DBI抗体在暗光箱和开放视野测试中均不会影响小鼠的行为。相反，ACBP / DBI在强迫游泳试验中增加了不动，而抗ACBP / DBI抗体则抵消了这种抑郁症状。在诊断出患有抗药性双相情感障碍或精神分裂症的患者中，ACBP / DBI与体重指数（BMI）类似相关，与精神病学诊断无关。多变量分析表明，ACBP / DBI水平高的患者有血脂异常的危险，这种作用独立于BMI。综上所述，