Guzmán-Ruiz Rocío, Stucchi Paula, Ramos Maria Pilar, Sevillano Julio, Somoza Beatriz, Fernández-Alfonso Marisol, Ruiz-Gayo Mariano
Departamento de Ciencias Farmacéuticas y de la Alimentación, Facultad de Farmacia, Universidad CEU-San Pablo, Madrid, Spain.
Endocrinol Nutr. 2012 Jun-Jul;59(6):354-61. doi: 10.1016/j.endonu.2012.04.001. Epub 2012 Jun 1.
Desensitization of leptin receptors is a process that specifically occurs in some tissues. We have hypothesized that during the development of obesity tissue lipids would increase gradually in particular organs depending on leptin responsiveness. Our aim was to establish a relationship between leptin resistance and lipid deposition by using a model of diet-induced obesity (DIO) and we have characterized, in mice undergoing a dietary treatment with a high-fat (HF) diet, the evolution of lipid content and leptin responsiveness in white adipose tissue and liver.
Four-week-old male C57BL/6J mice were divided into two groups and assigned either to a low-fat or to a high-fat diet. Dietary treatment lasted 8, 20 or 32 weeks. The last day animals received 1mg/kg leptin and then tissues were weighed and processed for Western-blotting and lipid determination.
We observed an initial increase of the relative weight of adipose pads that was blunted after 32-week HF. In contrast, liver size exhibited an initial decrease followed by a progressive increase, which was coincident with the increase of hepatic triglycerides and with the impairment of leptin receptor signalling.
Our data show that leptin resistance within white adipose tissue does not deal with an increase of the size of adipose pads and suggest that consequences of leptin resistance, in terms of fat accumulation, are tissue-dependent.
瘦素受体脱敏是一个在某些组织中特异性发生的过程。我们推测在肥胖发展过程中，特定器官的组织脂质会根据瘦素反应性逐渐增加。我们的目的是通过饮食诱导肥胖（DIO）模型建立瘦素抵抗与脂质沉积之间的关系，并在接受高脂肪（HF）饮食治疗的小鼠中，表征白色脂肪组织和肝脏中脂质含量和瘦素反应性的演变。
将4周龄雄性C57BL/6J小鼠分为两组，分别给予低脂或高脂饮食。饮食治疗持续8、20或32周。在动物接受1mg/kg瘦素的最后一天，对组织进行称重，并进行蛋白质免疫印迹分析和脂质测定。
我们观察到脂肪垫相对重量最初增加，但在32周的HF饮食后变钝。相比之下，肝脏大小最初减小，随后逐渐增加，这与肝甘油三酯增加和瘦素受体信号传导受损相一致。
我们的数据表明，白色脂肪组织中的瘦素抵抗与脂肪垫大小增加无关，并表明就脂肪积累而言，瘦素抵抗的后果是组织依赖性的。
