![]() Among lipoproteins, low-density lipoproteins (LDL) play a critical role in the early-onset of the disease. 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.Ītherosclerosis is characterized by the accumulation of lipoprotein-derived cholesterol in the arterial wall ( Hegele, 2009 Goldstein and Brown, 2015). These results indicate that hypothalamic PSA controls plasma lipoprotein profile by circumventing the rise of LDL-to-HDL cholesterol ratio in plasma during overfeeding. Importantly, we found that hypothalamic PSA removal aggravated LDL elevation and reduced HDL levels upon HFD. Although plasma VLDL-cholesterol was normalized within the first week, LDL and HDL were still elevated after 2 weeks upon HFD. We report that HFD consumption in mice rapidly increased plasma cholesterol, including VLDL, LDL, and HDL-cholesterol. In this work, we investigated the role of hypothalamic PSA in the regulation of plasma cholesterol levels and distribution. In the hypothalamus, PSA is involved in many aspects of energy balance including food intake, osmoregulation, circadian rhythm, and sleep. ![]() In the brain, PSA modulates distances between cells and controls the plasticity of the nervous system. The polysialic acid (PSA) is a large glycan that is added to cell-surface proteins during their post-translational maturation. 2Institut National de la Santé et de la Recherche Médicale LNC, U1231, Université Bourgogne-Franche Comté, LipSTIC LabEx, Fondation de Coopération Scientifique Bourgogne-Franche Comté, Dijon, France.1AgroSup Dijon, Centre National de la Recherche Scientifique, Institut National de la Recherche Agronomique, Université Bourgogne-Franche Comté, Dijon, France.Xavier Brenachot 1, Thomas Gautier 2, Emmanuelle Nédélec 1, Valérie Deckert 2, Amélie Laderrière 1, Danaé Nuzzaci 1, Caroline Rigault 1, Aleth Lemoine 1, Luc Pénicaud 1, Laurent Lagrost 2 and Alexandre Benani 1 *
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