Santos M José Luis
Departamento de Nutrición, Diabetes y Metabolismo, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Rev Med Chil. 2009 Sep;137(9):1225-34.
Obesity is a multifactorial disease that is rarely associated to single gene defects. However, due to their direct cause-effect relationships, those genetic defects that cause some forms of monogenic obesity are relevant in the study of mechanisms that contribute to increased energy intake and body fat accumulation. Most of the genes that have been shown to cause monogenic obesity are related to the leptin-melanocortin system. The functionality of this system has been elucidated through natural mutations (Agouti, ob and db) in mice and knock-out models. Mutations related to human monogenic obesity have been described in leptin, leptin receptor, proopiomelanocortin, prohormone convertase 1 or melanocortin receptor 4 genes. Therapy with human recombinant leptin in patients with genetic deficiency of the hormone is an effective medical treatment of obesity, although only applicable to very few families. The use of leptin-melanocortin agonists, drugs to avoid leptin resistance or combinations of treatments with leptin and other satiating peptides are currently being investigated for multifacotiral human obesity.
肥胖是一种多因素疾病，很少与单基因缺陷相关。然而，由于其直接的因果关系，那些导致某些形式单基因肥胖的基因缺陷在促成能量摄入增加和体脂积累的机制研究中具有相关性。大多数已被证明会导致单基因肥胖的基因都与瘦素 - 黑皮质素系统有关。该系统的功能已通过小鼠的自然突变（刺鼠、ob 和 db）和基因敲除模型得以阐明。与人类单基因肥胖相关的突变已在瘦素、瘦素受体、阿黑皮素原、激素原转化酶 1 或黑皮质素受体 4 基因中被描述。对激素基因缺乏的患者使用重组人瘦素进行治疗是一种有效的肥胖医学疗法，尽管仅适用于极少数家庭。目前正在研究使用瘦素 - 黑皮质素激动剂、避免瘦素抵抗的药物或瘦素与其他饱腹感肽的联合治疗方法来治疗多因素引起的人类肥胖。
