瑞典卡罗林斯卡医学院15日宣布，该机构专家发现心脏血管和肌肉能自发调节日常摄入食物中的脂肪酸，这对治疗包括Ⅱ型糖尿病在内的新陈代谢疾病有重要意义。
卡罗林斯卡医学院的研究人员用老鼠进行了实验，他们将VEGF－B蛋白质作为从肌肉到血管壁的传导信号，对其生物功能进行测试后发现，该蛋白质能控制血管壁中的脂肪酸运输蛋白质（FATPs）的数量。
瑞典专家指出，当FATPs蛋白质增多时，从血管壁穿过并被摄入的脂肪也相应迅速增加。那些血管壁中缺乏VEGF－B蛋白质受体的老鼠，其肌肉和心脏中摄入的脂肪较少，在不同机体组织中积聚的脂肪也比较少。
研究项目负责人、卡罗林斯卡医学院的医药生物化学和生物物理学教授乌尔夫埃里克松说，由于肌肉中的脂肪过度增加是造成人体出现胰岛素抵抗进而罹患Ⅱ型糖尿病的重要原因，因此上述发现对于治疗包括Ⅱ型糖尿病在内的新陈代谢疾病有重要意义。这一研究成果已发表在最新一期英国《自然》Nature杂志上。
据埃里克松等人介绍，下一步他们将致力于研究如何影响胰岛素信号，并且通过调节VEGF－B蛋白质信号来降低患糖尿病老鼠的血液葡萄糖水平。
生物谷推荐原文出处：
Nature doi:10.1038/nature08945
Vascular endothelial growth factor B controls endothelial fatty acid uptake
Carolina E. Hagberg1,2, Annelie Falkevall1,2, Xun Wang1,2, Erik Larsson3, Jenni Huusko4, Ingrid Nilsson1, Laurens A. van Meeteren5, Erik Samen6,7, Li Lu7, Maarten Vanwildemeersch1,2, Joakim Klar2,5, Guillem Genove8, Kristian Pietras1,2, Sharon Stone-Elander6,7, Lena Claesson-Welsh5, Seppo Yl?-Herttuala4, Per Lindahl3,9 " Ulf Eriksson1,2
Tissue Biology Group, Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, SwedenLudwig Institute for Cancer Research Ltd, Stockholm Branch, Karolinska Institutet, Box 240, SE-171 77 Stockholm, Sweden
Institute of Biomedicine, University of Gothenburg, Box 440, SE-405 30 Gothenburg, Sweden
Department of Biotechnology and Molecular Medicine, A.I. Virtanen Institute, University of Kuopio, Box 1627, FIN-70211 Kuopio, Finland
Uppsala University, Department of Genetics and Pathology, Rudbeck Laboratory, SE-751 85 Uppsala, Sweden
Karolinska Pharmacy, Karolinska University Hospital, Solna, SE-17176 Stockholm, Sweden
Clinical Neurosciences, Karolinska Institutet, SE-171 76 Stockholm, Sweden
Laboratory of Vascular Biology, Division of Matrix Biology, Department of Medical Biochemistry and Biophysics, Karolinska Institutet, SE-171 77 Stockholm, Sweden
Wallenberg Laboratory for Cardiovascular Research, Bruna Str?ket 16, Sahlgrenska University Hospital, SE-413 45 Gothenburg, Sweden
The vascular endothelial growth factors (VEGFs) are major angiogenic regulators and are involved in several aspects of endothelial cell physiology1. However, the detailed role of VEGF-B in blood vessel function has remained unclear2, 3. Here we show that VEGF-B has an unexpected role in endothelial targeting of lipids to peripheral tissues. Dietary lipids present in circulation have to be transported through the vascular endothelium to be metabolized by tissue cells, a mechanism that is poorly understood4. Bioinformatic analysis showed that Vegfb was tightly co-expressed with nuclear-encoded mitochondrial genes across a large variety of physiological conditions in mice, pointing to a role for VEGF-B in metabolism. VEGF-B specifically controlled endothelial uptake of fatty acids via transcriptional regulation of vascular fatty acid transport proteins. As a consequence, Vegfb-/- mice showed less uptake and accumulation of lipids in muscle, heart and brown adipose tissue, and instead shunted lipids to white adipose tissue. This regulation was mediated by VEGF receptor 1 and neuropilin 1 expressed by the endothelium. The co-expression of VEGF-B and mitochondrial proteins introduces a novel regulatory mechanism, whereby endothelial lipid uptake and mitochondrial lipid use are tightly coordinated. The involvement of VEGF-B in lipid uptake may open up the possibility for novel strategies to modulate pathological lipid accumulation in diabetes, obesity and cardiovascular diseases.
