| Background: Obesity is a severely public health problem the whole society faces, and it is correlated closely with many diseases, such as diabetes 2, hypertension,coronary heart disease,gallstone, and so on. Leptin is secreted mostly by white adipocytes into the circulation and is involved in negative feedback loop from adipose storage to hypothalamus.The role of leptin is increasing satiety and energy expenditure.Scientis have found that the level of leptin were high in obese people suggesting obese exist leptin resistance. Experiments found that injecting leptin to central nerve of diet-induced obese rats,the rats do not become thin.All the facts suggest an inhibitory regulation at the level of the leptin receptor or downstream signaling pathway.After leptin binds leptin receptor(OB-Rb),leptin plays role through activing Janus kinase (Janus)/ signal transducers and activators of transcription(STAT)pathway. As the major negative factors of JAK/STAT pathway, suppressors-of-cytokine-signaling 3(SOCS-3) likely to be involved in the leptin resistance. High fat-induced obese rats also exist insulin resistance,because insulin and leptin have the same signal transduc- tion pathway, SOCS-3 is thus likely to be involved in the insulin resist- ance.We observe serum leptin and insulin level as well as expression of SOCS-3mRNA and OB-RbmRNA in hypothalamus of high fat diet-induced obese SD rats . The present study was to research whether there are relationships between hyperleptinemia,hyperinsulinemia and SOCS-3 mRNA in hypothalamus in high fat diet-induced obese SD rats.Objectives: To imitate the feature of children obesity, 4-week-old (equal to juvenile stage)SD rats were selected as rodent in the experime-nt .One of them were fed with high-fat diet to set up the animal model of dietary obesity. We study the changes of leptin and insulin as well as expression of SOCS-3mRNA in hypothalamus. From the aspects of regulation in receptor and post-receptor signal transduction pathway, we try to probe into the possible pathogenesis of children leptin resistance and insulin resistance and to study the relationship between SOCS-3mRNA expression and serum leptin,insulin concentrations and OB-RbmRNA respectively. The purpose of this experiment is researching the possible pathogenesis of children leptin resistance and insulin resistance on the ground of rodrnt models.Methods:Thirty two four-week-old healthy male SD rats were divided into two groups randomly. One (20) acting as experimental group fed with high-fat diet to set up the animal model of dietary obesity; the other (12) serving as control group fed with ordinary diet.Body weights were monitored weekly. At the end of 8 weeks, obese group was obtained according to the standard that average body weight go beyond 20% compar- ed with the control. For both obese and control rats, serum leptin,serum insulin and C peptide were measured with radioimmunity; expression of OB-Rb, SOCS-3mRNA in the hypothalamus was detected with semiquantita tive RT-PCR(usingβ-actin as an internal standard).Results:1 .Rats fed with high-fat diet were observed significant increases in body weight from 4 weeks of high-fat diet administration compared with control group. At the end of 8 weeks, according to the standard above, 15 rats were diet-induced-obesity rats and treated as obese group. There were higher levels of glucose , triglyceride and cholesterol obese group.2 . The concentrations of serum leptin,insulin and C peptide in rats of obese group were elevated obviously compared with control group.There were significant negative relationship between serum leptin concentrations and serum insulin(r=0.608 P<0.01), C peptide(r=0686 P<0.01)concentration in obese group.3. The expression (relative gray value) of OB-RbmRNA in obese group were reduced markedly compared with the control group and there were significant negative relationship between OB-Rb mRNA expression inhypothalamus and serum leptin concentrations in obese group (r =-0.718, P<0.01).4. SOCS-3 existed both in hypothalamus of two groups. The expression (relative gray value) of SOCS-3mRNA in obese group were increased markedly compared with the control group and there were significant positive relationship between SOCS-3 mRNA expression in hypothalamus and serum leptin(r=0.666 P<0.01),insulin(r=0.560 P<0.05) concentrations in obese group.5. There were not significant positive relationship between OB-Rb mRNA expression and SOCS-3 mRNA expression in hypothalamus (r=-0.494 P>0.05) in obese group.Conclusion:1. Serum leptin levels increased in obese rats, suggesting that high-fat diet may lead to leptin resistance.2. Levels of glucose and serum insulin levels increased in obese rats, suggesting that high-fat diet may lead to insulin resistance.3. The expression of OB-Rb mRNA in obese group was reduced remarkably as compared with the control group, and there was significant negative relationship between OB-Rb mRNA expression in hypothalamus and serum leptin concentrations in obese group, suggesting the down-regulation of OB-Rb in hypothalamus maybe act as one of the factors that result in leptin resistance in obese rats.4. The expression of SOCS-3 mRNA in obese group was increased remarkably as compared with the control group, and there was significant positive relationship between SOCS-3 mRNA expression in hypothalamus and serum leptin,insulin concentrations in obese group.The upregulation of SOCS-3 expression may act as the negative Factors of JAK/STAT pathway that result in leptin resistance and insulin resistance in obese rats.
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