Bergman Richard N, Kim Stella P, Hsu Isabel R, Catalano Karyn J, Chiu Jenny D, Kabir Morvarid, Richey Joyce M, Ader Marilyn
Department of Physiology and Biophysics, Keck School of Medicine, University of Southern California, Los Angeles, California 90033, USA.
Am J Med. 2007 Feb;120(2 Suppl 1):S3-8; discussion S29-32. doi: 10.1016/j.amjmed.2006.11.012.
Visceral adiposity has been identified as an independent risk factor for cardiovascular disease and the so-called metabolic syndrome. The canine obesity model closely recapitulates the correlation between human visceral adiposity and insulin resistance. A recent canine study indicates that insulin expands the volume of distribution associated with skeletal muscle, and that its ability to enhance macromolecular distribution within this space is blunted in the fat-fed obese canine model. Our canine study supports the portal theory of insulin resistance, in which free fatty acids (FFAs) from visceral fat directly enter the liver and have a detrimental effect on insulin action. The role of adipokines in this condition remains less clear. Sympathetic nervous system hyperactivity in obesity may also contribute to excessive FFA release, hypertension, and insulin resistance. Pathologies interrelated with insulin resistance include beta-cell hypersecretion, reduced insulin clearance, and resultant hyperinsulinemia. An observed nocturnal increase in plasma FFA levels may account for both insulin resistance and compensatory hyperinsulinemia and warrants further investigation. The elucidation of these interrelated pathologies may help reveal points where medical intervention can reduce metabolic disease.
内脏脂肪过多已被确认为心血管疾病和所谓代谢综合征的独立危险因素。犬类肥胖模型密切再现了人类内脏脂肪过多与胰岛素抵抗之间的相关性。最近一项针对犬类的研究表明，胰岛素会扩大与骨骼肌相关的分布容积，并且在高脂喂养的肥胖犬类模型中，其增强该空间内大分子分布的能力会减弱。我们对犬类的研究支持胰岛素抵抗的门静脉理论，即来自内脏脂肪的游离脂肪酸（FFA）直接进入肝脏并对胰岛素作用产生不利影响。脂肪因子在这种情况下的作用仍不太清楚。肥胖时交感神经系统功能亢进也可能导致游离脂肪酸过度释放、高血压和胰岛素抵抗。与胰岛素抵抗相关的病理状况包括β细胞分泌过多、胰岛素清除率降低以及由此导致的高胰岛素血症。观察到的夜间血浆游离脂肪酸水平升高可能是胰岛素抵抗和代偿性高胰岛素血症的原因，值得进一步研究。阐明这些相互关联的病理状况可能有助于揭示医学干预可降低代谢性疾病的关键点。
