酰基辅酶A结合蛋白(ACBP):将自噬与食物摄入联系起来的难以捉摸的“饥饿因子”

IF 4.1 Q2 CELL BIOLOGY
José Manuel Bravo-San Pedro, Valentina Sica, Frank Madeo, Guido Kroemer
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引用次数: 0

摘要

在啮齿类动物中发现的最著名的食欲调节因子是食欲抑制剂瘦素和食欲刺激因子胃饥饿素。在人类肥胖中,已经记录了影响瘦素及其受体的罕见功能缺失突变,以及与胃促生长素及其受体有关的多态性,这显然证实了瘦素和胃促生长素与人类生理学的相关性。然而,矛盾的是,绝大多数肥胖者表现出高瘦素和低胃饥饿素血浆水平,这表明这两个因素与疾病无关。我们最近发现酰基辅酶A结合蛋白(ACBP),也称为地西泮结合抑制剂(DBI),在小鼠中是一种有效的脂肪生成和食欲刺激因子。事实上,作为对饥饿的反应,ACBP/DBI以自噬依赖的方式从组织中释放,并在血浆中增加。静脉注射ACBP/DBI通过降低循环葡萄糖水平和随后激活下丘脑中的食欲神经元来刺激进食行为。相反,ACBP/DBI的中和消除了小鼠饥饿后观察到的高吞噬。值得注意的是,肥胖者和小鼠的血浆中ACBP/DBI增加,这表明其在食欲刺激中的作用与人类肥胖之间存在趋同(而非分歧)。基于我们的研究结果,我们假设了一种新的“饥饿反射”,即饥饿诱导细胞外ACBP/DBI激增,进而刺激进食行为。因此,ACBP/DBI可能是解释肥胖患者食物摄入增加的难以捉摸的“饥饿因素”。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Acyl-CoA-binding protein (ACBP): the elusive 'hunger factor' linking autophagy to food intake.

The best-known appetite-regulating factors identified in rodents are leptin, an appetite inhibitor, and ghrelin, an appetite stimulator. Rare cases of loss-of-functions mutations affecting leptin and its receptor, as well as polymorphisms concerning ghrelin and its receptor, have been documented in human obesity, apparently validating the relevance of leptin and ghrelin for human physiology. Paradoxically, however, the overwhelming majority of obese individuals manifest high leptin and low ghrelin plasma levels, suggesting that both factors are not directly disease-relevant. We recently discovered that acyl-CoA-binding protein (ACBP), also known as diazepam-binding inhibitor (DBI), acts as an efficient lipogenic and appetite stimulator in mice. Indeed, in response to starvation, ACBP/DBI is released from tissues in an autophagy-dependent fashion and increases in the plasma. Intravenous injection of ACBP/DBI stimulates feeding behavior through a reduction of circulating glucose levels, and consequent activation of orexigenic neurons in the hypothalamus. In contrast, neutralization of ACBP/DBI abolishes the hyperphagia observed after starvation of mice. Of note, ACBP/DBI is increased in the plasma of obese persons and mice, pointing to a convergence (rather than divergence) between its role in appetite stimulation and human obesity. Based on our results, we postulate a novel 'hunger reflex' in which starvation induces a surge in extracellular ACBP/DBI, which in turn stimulates feeding behavior. Thus, ACBP/DBI might be the elusive 'hunger factor' that explains increased food uptake in obesity.

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来源期刊
Cell Stress
Cell Stress Biochemistry, Genetics and Molecular Biology-Biochemistry, Genetics and Molecular Biology (miscellaneous)
CiteScore
13.50
自引率
0.00%
发文量
21
审稿时长
15 weeks
期刊介绍: Cell Stress is an open-access, peer-reviewed journal that is dedicated to publishing highly relevant research in the field of cellular pathology. The journal focuses on advancing our understanding of the molecular, mechanistic, phenotypic, and other critical aspects that underpin cellular dysfunction and disease. It specifically aims to foster cell biology research that is applicable to a range of significant human diseases, including neurodegenerative disorders, myopathies, mitochondriopathies, infectious diseases, cancer, and pathological aging. The scope of Cell Stress is broad, welcoming submissions that represent a spectrum of research from fundamental to translational and clinical studies. The journal is a valuable resource for scientists, educators, and policymakers worldwide, as well as for any individual with an interest in cellular pathology. It serves as a platform for the dissemination of research findings that are instrumental in the investigation, classification, diagnosis, and therapeutic management of major diseases. By being open-access, Cell Stress ensures that its content is freely available to a global audience, thereby promoting international scientific collaboration and accelerating the exchange of knowledge within the research community.
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