| Background: For the past few years, with the improvement of standard of living and change of meal structure, obesity in children put up the increased trend step by step. Obesity not only influences the health of children, but also as a high dangerous factor for diabetes 2, cardiac and cerebrovascular disease of adult. The discovery of obese gene made a great progress on studying of obesity. Leptin, as the product of obese gene, plays an important role in regulating food intake and energy consuming, in order to keep the relative balance of body fat. Leptin effects through it's receptor OB-R. Although it has been shown that leptin defect would lead to obesity in human and rodents, almost all of those obese subjects aren't short of it. On the contrary, hyperleptinemia namely high level of leptin exists in their bodies. The phenomenon of low or no reaction to leptin is called leptin resistance, reveals a closer relationship between obesity and leptin resistance. Objectives: To imitate the feature of children obesity, 4-week-old (equal to juvenile stage) SD rats were selected as rodent model in the experiment. Serum leptin levels as well as expression of long and short leptin receptor isoforms (OB-Rb, OB-Ra) mRNA in central (hypothalamus) and peripheral tissue (liver) of obese SD rats fed with high-fat diet were observed. From the aspect of OB-R mRNA regulation, we study the changes of leptin and it's receptors in obese rats, in order to probe into the possible pathogenesis of children leptin resistance on the ground of rodent models. Methods: Thirty 4-week-old healthy male SD rats were divided into two groups randomly. One (20) acting as experimental group fed with high-fat diet containing 20% lard; the other (10) serving as control group fed with ordinary diet. At the end of 8 weeks, obese group was obtained according to the standard that average body weight go beyond 20% compared with the control. For both obese and control rats, serum leptin concentrations were measured with enzyme immunoassay; expression of OB-Ra, OB-Rb mRNA in hypothalamus and liver was detected with semi-quantitative RT-PCR. Results: 1.The increase of body weight in SD rats fed with high-fat diet was evident compared with control group fed with ordinary diet. After feeding 4 weeks, the difference became remarkably (P<0.01). At the end of 8 weeks, according to the standard above, 14 rats fed with high-fat diet became obese rat models, acting as obese group. 2.The levels of serum leptin in rats of obese group were elevated significantly compared with the control (P<0.05). 3.Long and short leptin receptor isoforms existed both in hypothalamus and liver of two groups. In these two sites, expression of OB-Ra, OB-Rb mRNA of obese group was reduced markedly compared with the control, and there were significant differences between two groups (P<0.01). OB-Rb expressed mainly in hypothalamus, while OB-Ra expressed mainly in liver. 4.There were marked negative correlations between serum leptin concentrations and OB-Ra, OB-Rb mRNA expression (relative gray value) in hypothalamus and liver of obese group, the r2 are 0.743, 0.751, 0.712 and 0.774 respectively (P<0.01).Conclusions: 1.Obese rat models can be set up through feeding with high-fat diet. 2.Serum lepin levels increased in obese rats, suggesting that high-fat diet may lead to leptin resistance. 3.Long and short leptin receptor isoforms expressed both in central (hypothalamus) and peripheral tissue (liver), and OB-Rb expressed mainly in hypothalamus, while OB-Ra expressed mainly in liver. 4.The downregulation of OB-R's expression may act as one of the factors that result in leptin resistance in obese rats.
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