Laboratory of Molecular Biology, University of the Balearic Islands, Palma de Mallorca, Spain.
Int J Obes (Lond). 2010 May;34(5):809-19. doi: 10.1038/ijo.2010.18. Epub 2010 Feb 16.
The intake of leptin during the suckling period protects against obesity and improves insulin and central leptin sensitivity in adult rats.
We analyzed whether leptin treatment to neonates may also improve later peripheral leptin sensitivity in adipose tissue under high-fat (HF) diet conditions.
Male rats were supplemented with a daily oral dose of leptin or the vehicle (controls) during the suckling period. After weaning, animals were fed a normal-fat or an HF diet until the age of 6 months. At this age, mRNA and protein levels of the long-form leptin receptor (OB-Rb) and the expression of other genes related with energy metabolism were measured in various adipose depots (inguinal, mesenteric and retroperitoneal).
HF-diet feeding resulted in lower OB-Rb mRNA and protein levels in internal depots in controls but not in leptin-treated animals; these animals maintained OB-Rb mRNA and protein levels under HF-diet conditions in these depots, particularly in the mesenteric one, and this was accompanied by increased expression of genes related with energy uptake (GLUT4, CD36), fatty acid oxidation (peroxisome proliferator activated receptor-alpha (PPARalpha), CPT1, UCP3) and lipogenesis (PPARgamma, GPAT). Leptin-treatment also ameliorated HF-diet-induced hepatic fat accumulation occurring in control animals.
Leptin treatment during the suckling period may improve the lasting effects of HF-diet feeding on leptin receptor abundance in the adipose tissue and increase its oxidative capacity, resulting in a better handling and partitioning of excess fuel. This, together with the described improvement of central leptin sensitivity, may explain why these animals are more protected against diet-induced obesity and its metabolic-related disorders.
哺乳期摄入瘦素可预防肥胖，并提高成年大鼠的胰岛素和中枢瘦素敏感性。
我们分析了新生儿接受瘦素治疗是否也能改善高脂肪（HF）饮食条件下脂肪组织后期外周瘦素敏感性。
雄性大鼠在哺乳期每天接受口服瘦素或载体（对照组）补充。断奶后，动物喂食正常脂肪或 HF 饮食，直至 6 月龄。此时，在各种脂肪组织（腹股沟、肠系膜和腹膜后）中测量长型瘦素受体（OB-Rb）的 mRNA 和蛋白水平以及与能量代谢相关的其他基因的表达。
HF 饮食喂养导致对照组内脏脂肪组织中 OB-Rb mRNA 和蛋白水平降低，但在接受瘦素治疗的动物中没有降低；这些动物在这些脂肪组织中维持了 OB-Rb mRNA 和蛋白水平在 HF 饮食条件下，特别是在肠系膜脂肪组织中，并且伴随着与能量摄取（GLUT4、CD36）、脂肪酸氧化（过氧化物酶体增殖物激活受体-α（PPARα）、CPT1、UCP3）和脂肪生成（PPARγ、GPAT）相关的基因表达增加。瘦素治疗还改善了对照组动物中 HF 饮食引起的肝脂肪堆积。
哺乳期接受瘦素治疗可能改善 HF 饮食喂养对脂肪组织中瘦素受体丰度的持久影响，并增加其氧化能力，从而更好地处理和分配多余的燃料。这与描述的中枢瘦素敏感性的改善一起，可能解释了为什么这些动物对饮食引起的肥胖及其代谢相关疾病更具保护作用。
