Brenachot Xavier, Gautier Thomas, Nédélec Emmanuelle, Deckert Valérie, Laderrière Amélie, Nuzzaci Danaé, Rigault Caroline, Lemoine Aleth, Pénicaud Luc, Lagrost Laurent, Benani Alexandre
AgroSup Dijon, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Université Bourgogne-Franche ComtéDijon, France.
Institut National de la Santé et de la Recherche Médicale LNC, U1231, Université Bourgogne-Franche Comté, LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche ComtéDijon, France.
Front Neurosci. 2017 May 3;11:245. doi: 10.3389/fnins.2017.00245. eCollection 2017.
The polysialic acid (PSA) is a large glycan that is added to cell-surface proteins during their post-translational maturation. In the brain, PSA modulates distances between cells and controls the plasticity of the nervous system. In the hypothalamus, PSA is involved in many aspects of energy balance including food intake, osmoregulation, circadian rhythm, and sleep. In this work, we investigated the role of hypothalamic PSA in the regulation of plasma cholesterol levels and distribution. We report that HFD consumption in mice rapidly increased plasma cholesterol, including VLDL, LDL, and HDL-cholesterol. Although plasma VLDL-cholesterol was normalized within the first week, LDL and HDL were still elevated after 2 weeks upon HFD. Importantly, we found that hypothalamic PSA removal aggravated LDL elevation and reduced HDL levels upon HFD. These results indicate that hypothalamic PSA controls plasma lipoprotein profile by circumventing the rise of LDL-to-HDL cholesterol ratio in plasma during overfeeding. Although mechanisms by which hypothalamic PSA controls plasma cholesterol homeostasis remains to be elucidated, these findings also suggest that low level of hypothalamic PSA might be a risk factor for dyslipidemia and cardiovascular diseases.
多唾液酸（PSA）是一种在细胞表面蛋白翻译后成熟过程中添加的大型聚糖。在大脑中，PSA调节细胞间距离并控制神经系统的可塑性。在下丘脑，PSA参与能量平衡的许多方面，包括食物摄入、渗透压调节、昼夜节律和睡眠。在这项研究中，我们研究了下丘脑PSA在调节血浆胆固醇水平和分布中的作用。我们报告，小鼠食用高脂饮食（HFD）后，血浆胆固醇迅速升高，包括极低密度脂蛋白（VLDL）、低密度脂蛋白（LDL）和高密度脂蛋白胆固醇（HDL）。尽管血浆VLDL胆固醇在第一周内恢复正常，但在HFD喂养2周后，LDL和HDL仍然升高。重要的是，我们发现去除下丘脑PSA会加重HFD喂养后LDL的升高并降低HDL水平。这些结果表明，下丘脑PSA通过避免过度喂养期间血浆中LDL与HDL胆固醇比值的升高来控制血浆脂蛋白谱。尽管下丘脑PSA控制血浆胆固醇稳态的机制仍有待阐明，但这些发现也表明下丘脑PSA水平低可能是血脂异常和心血管疾病的危险因素。
