Muoio Deborah M, Newgard Christopher B
Sarah W. Stedman Nutrition and Metabolism Center and Departments of Pharmacology and Cancer Biology, Medicine, Duke University Medical Center, Durham, North Carolina 27704, USA.
Annu Rev Biochem. 2006;75:367-401. doi: 10.1146/annurev.biochem.75.103004.142512.
An epidemic surge in the incidence of obesity has occurred worldwide over the past two decades. This alarming trend has been triggered by lifestyle habits that encourage overconsumption of energy-rich foods while also discouraging regular physical activity. These environmental influences create a chronic energy imbalance that leads to persistent weight gain in the form of body fat and a host of other abnormalities in metabolic homeostasis. As adiposity increases, so does the risk of developing comorbidities such as diabetes, hypertension, and cardiovascular disease. The intimate association between obesity and systemic metabolic dysregulation has inspired a new area of biochemistry research in which scientists are seeking to understand the molecular mechanisms that link chronic lipid oversupply to tissue dysfunction and disease development. The purpose of this chapter is to review recent findings in this area, placing emphasis on lipid-induced functional impairments in the major peripheral organs that control energy flux: adipose tissue, the liver, skeletal muscle, and the pancreas.
在过去二十年中，全球肥胖症发病率呈流行趋势激增。这一令人担忧的趋势是由生活方式习惯引发的，这些习惯一方面鼓励过度食用高能量食物，另一方面又不鼓励定期进行体育活动。这些环境因素造成了慢性能量失衡，导致以体脂形式出现的持续体重增加以及代谢稳态中的一系列其他异常情况。随着肥胖程度的增加，患糖尿病、高血压和心血管疾病等合并症的风险也随之增加。肥胖与全身代谢失调之间的密切关联激发了生物化学研究的一个新领域，科学家们正在该领域探索将慢性脂质供应过剩与组织功能障碍和疾病发展联系起来的分子机制。本章的目的是回顾该领域的最新研究成果，重点关注脂质诱导的对控制能量通量的主要外周器官（脂肪组织、肝脏、骨骼肌和胰腺）的功能损害。
