The obesity pandemic:: Where have we been and where are we going?
The obesity pandemic:: Where have we been and where are we going?
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DOI：
10.1038/oby.2004.273
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发表时间：
2004-11-01
期刊：
影响因子：
--
通讯作者：
Lowell, BC
中科院分区：
文献类型：
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作者：
Roth, J;Qiang, XL;Lowell, BC
肥胖是一种新的流行病，与死亡、发病和加速衰老的风险增加有关。用于促进体重减轻的多种治疗方式被谨慎地概述，特别是对于非常年轻或年老的患者。除了非常罕见的单基因缺陷外，肥胖的遗传是复杂的，尽管进行了积极的研究，但仍然知之甚少。揭示肥胖症的病理生理学的最新进展是认识到1）过量脂肪沉积在肝脏、肌肉和胰岛中; 2）脂肪组织分泌大量活性信号传导分子，包括瘦素、脂联素和脂联素，以及游离脂肪酸;和3）活化的巨噬细胞定殖脂肪组织。在肥胖的原因和后果中起关键作用的其他候选人包括：1）代谢程序，其中食物充当发育调节剂; 2)被称为“代谢综合征”的一系列缺陷; 3）脂肪组织中皮质醇过度产生;特别是4）胰岛素抵抗。胰岛素抵抗的可能病因包括细胞因子过量、游离脂肪酸升高和高胰岛素血症本身，如小鼠中胰岛素的转基因过量生产。
Obesity, a new pandemic, is associated with an increased risk of death, morbidity, and accelerated aging. The multiple therapeutic modalities used to promote weight loss are outlined with caution, especially for patients who are very young or old. Except for very rare single gene defects, the inheritance of obesity is complex and still poorly understood, despite active investigations. Recent advances that have shed light on the pathophysiology of obesity are the recognition that 1) excess fat is deposited in liver, muscle,, and pancreatic islets; 2) fat tissue secretes a large number of active signaling molecules including leptin, adiponectin, and resistin, as well as free fatty acids; and 3) activated macrophages colonize the adipose tissue. Other candidates for key roles in the causes and consequences of, obesity include 1) metabolic programming, where food acts as a developmental regulator;. 2) the constellation of defects known as the "metabolic syndrome;" 3) cortisol overproduction in the adipose tissue; and especially, 4) insulin resistance. The possible etiologies of insulin resistance include cytokine excess, elevated free fatty acids, and hyper-insulinemia itself, as with transgenic overproduction of insulin in mice.