Metabolic Research Laboratories, Institute of Metabolic Science, University of Cambridge, Addenbrooke’s Hospital, Cambridge CB2 OQQ, United Kingdom.
Endocrinology. 2011 Feb;152(2):476-82. doi: 10.1210/en.2010-0911. Epub 2011 Jan 5.
Low birth weight and rapid postnatal weight gain are independent and additive risk factors for the subsequent development of metabolic disease. Despite an abundance of evidence for these associations, mechanistic data are lacking. The hormone leptin has received significant interest as a potential programming factor, because differences in the profile of leptin in early life have been associated with altered susceptibility to obesity. Whether leptin alone is a critical factor for programming obesity has, until now, remained unclear. Using the leptin-deficient ob/ob mouse, we show that low birth weight followed by rapid catch-up growth during lactation (recuperated offspring) leads to a persistent increase in body weight in adult life, both in wild-type and ob/ob animals. Furthermore, recuperated offspring are hyperphagic and epididymal fat pad weights are significantly increased, reflecting greater adiposity. These results show definitively that factors other than leptin are crucial in the programming of energy homeostasis in this model and are powerful enough to alter adiposity in a genetically obese strain.
低出生体重和快速的产后体重增加是代谢性疾病后续发展的独立和附加风险因素。尽管有大量证据表明存在这些关联，但缺乏机制数据。激素瘦素作为一种潜在的编程因素受到了广泛关注，因为生命早期瘦素的特征差异与肥胖易感性的改变有关。到目前为止，瘦素是否是导致肥胖的关键因素还不清楚。使用瘦素缺乏型 ob/ob 小鼠，我们发现低出生体重，随后在哺乳期快速追赶生长（恢复生长的后代）会导致成年期体重持续增加，在野生型和 ob/ob 动物中都是如此。此外，恢复生长的后代表现出过度进食，附睾脂肪垫重量显著增加，这反映了更大的肥胖程度。这些结果明确表明，在该模型中，除了瘦素之外，其他因素对于能量平衡的编程至关重要，并且强大到足以改变遗传肥胖品系的肥胖程度。
