Bray G A
Pennington Biomedical Research Center, Baton Rouge, Louisiana, USA.
Clin Cornerstone. 1999;2(3):1-15. doi: 10.1016/s1098-3597(99)90001-7.
Obesity results from a greater consumption of energy than is used by the body. As this energy is stored, fat cells enlarge, producing the characteristic pathology of obesity. The pathologic enlargement of fat cells, in turn, produces altered levels of many peptide and nutrient signals that are responsible for the disease we call "obesity." The genetic makeup of human beings, which reflects a long history of relative scarcity of foodstuffs, has run into an age of surfeit, and many people cannot readily adapt. Thus, the increased intake of food does not signal satiety, and there is a gradual increase in energy stores as intake of energy outpaces need as we grow older. Against this background of struggle between nature and nurture, it is possible to identify an increasing number of defects or etiologies that produce obesity. For most patients, however, it is not possible to connect obesity to a specific cause. Leptin deficiency and defects in the leptin receptor both produce human obesity. Defects in the pro-opiomelanocortin receptor system, the peroxisome proliferator-activated receptor-gamma, the agouti-related peptide, and a few other rare genetic syndromes are also associated with human obesity. Of the genetic causes, Prader-Willi syndrome is the most common. Hypothalamic injury following craniopharyngioma is the most common neuroendocrine cause. Endocrine disorders such as Cushing's disease, polycystic ovary disease, and growth-hormone deficiency can lead to increased body fat. In the modern world, exposure to a high-fat diet predisposes many people to obesity, and this problem is compounded by the low levels of activity now required for daily living. Treatment strategies must be developed against this background.
肥胖是由于摄入的能量超过了身体所消耗的能量所致。随着这些能量被储存起来，脂肪细胞会增大，从而产生肥胖的典型病理特征。脂肪细胞的病理性增大进而会导致许多肽类和营养信号水平发生改变，而这些信号与我们所说的“肥胖”这种疾病相关。人类的基因构成反映了长期以来食物相对匮乏的历史，如今却进入了一个食物过剩的时代，许多人难以轻易适应。因此，食物摄入量的增加并未带来饱腹感，随着年龄增长，当能量摄入超过需求时，能量储备会逐渐增加。在这种先天与后天因素相互作用的背景下，越来越多导致肥胖的缺陷或病因得以被识别出来。然而，对于大多数患者而言，无法将肥胖与特定病因联系起来。瘦素缺乏以及瘦素受体缺陷都会导致人类肥胖。促肾上腺皮质激素原受体系统、过氧化物酶体增殖物激活受体γ、刺鼠相关肽的缺陷以及其他一些罕见的遗传综合征也与人类肥胖有关。在遗传病因中，普拉德-威利综合征最为常见。颅咽管瘤术后下丘脑损伤是最常见的神经内分泌病因。库欣病、多囊卵巢病和生长激素缺乏等内分泌疾病可导致体脂增加。在现代社会，高脂饮食使许多人易患肥胖症，而如今日常生活所需的低活动水平又加剧了这一问题。必须在此背景下制定治疗策略。
