高脂喂养肥胖大鼠下丘脑及肝脏内细胞因子信号转导抑制物－3 mRNA表达的研究

doi:10.3877/cma.j.issn.1673-5250.2008.03.104

目的

瘦素抵抗被认为是儿童肥胖症的主要发病机制。细胞因子信号转导抑制物－3(suppressors－of－cytokine－signaling 3, SOCS3)作为瘦素受体后Janus蛋白激酶－信号转导及转录激活蛋白(JAK－STAT)信号传导通路的主要负性调节因子，可能参与瘦素抵抗的发生。本研究从瘦素受体基因表达和瘦素受体后Janus蛋白激酶－信号转录及转录激活蛋白传导通路水平，研究瘦素抵抗的可能发生机制。

方法

以高脂饮食制备幼年、雄性肥胖大鼠模型，利用半定量RT－PCR法检测肥胖大鼠下丘脑及肝脏组织内中细胞因子信号转导抑制物－3 mRNA、瘦素长型受体(OB－Rb)mRNA表达的改变，探讨细胞因子信号转导抑制物－3 mRNA表达与高瘦素血症及与瘦素长型受体mRNA表达的关系。

结果

与对照组相比，肥胖大鼠下丘脑及肝脏内，细胞因子信号转导抑制物－3表达升高(P<0.01)，并与血清瘦素水平呈正相关(r＝0.666，r＝0.790，P<0.01)。肥胖组大鼠下丘脑及肝脏内，细胞因子信号转导抑制物－3 mRNA(相对灰度值)与瘦素长型受体mRNA水平呈显著负相关(r＝－0.526，r＝－0.585，P<0.05)。

结论

肥胖大鼠中枢及外周组织的细胞因子信号转导抑制物－3表达上调，使瘦素受体后JAK－STAT信号转导通路抑制，可能参与了瘦素抵抗的发生机制。

关键词: 肥胖, 瘦素抵抗, 瘦素受体, 细胞因子信号转导抑制物－3

Objective

Leptin resistance is thought to be a main mechanism of child obesity. Suppressors-of-cytokine-signaling 3 (SOCS3) is a leptin inducible inhibitor of leptin signaling and a potential mediator of leptin resistance in obesity. From the aspect of expression in OB-Rb mRNA and post-receptor signal transduction pathway, we tried to probe the possible pathogenesis of leptin resistance.

Methods

4-week-old healthy male SD rats were fed with high-fat diet to set up the animal model of dietary obesity. Expressions of suppressors-of-cytokine-signaling 3 mRNA, OB-Rb mRNA in the hypothalamus and liver were detected with semi-quantitative RT-PCR. And the relationship between the expression of suppressors-of-cytokine-signaling 3 mRNA and serum leptin levels, between the expression of suppressors-of-cytokine-signaling 3 mRNA and OB-Rb mRNA were analyzed respectively.

Results

Compared with the control group, serum leptin levels were elevated obviously in the obese rat group (P<0.01), and the expression of suppressors-of-cytokine-signaling 3 mRNA in hypothalamus and liver were also increased remarkebly (P<0.01, respectively), and there was a significant positive correlation between serum leptin concentration and the suppressors-of-cytokine-signaling 3 mRNA level in the obese rat group (r=0.666, r=0.790, P<0.01, respectively). On the contrary, there were negative relationships between the expression of suppressors-of-cytokine-signaling 3 mRNA and OB-Rb mRNA in hypothalamus and liver (r=-0.526, r=-0.585, P<0.01, respectively).

Conclusion

To up-regulate the expression of suppressors-of-cytokine-signaling 3 mRNA may be related to leptin resistance in obese rats.

Key words: obesity, leptin resistance, leptin receptor, suppressors-of-cytokine-signaling 3(SOCS3)

图1　高脂饲养与普通饲料喂养SD大鼠的体重变化

图2　下丘脑及肝脏组织中SOCS3 mRNA RT－PCR产物电泳图

图3　下丘脑及肝脏组织中OB－Rb mRNA RT－PCR产物电泳图

	1　Pal R, Sahu A. Leptin signaling in the hypothalamus during chronic central leptin infusion. Endocrinology, 2003, 144(9)：3789－3798.
	2　Bjorbaek C, Elmquist J K, Frantz J D, et al. Identification of SOCS3 as a potential mediator of central leptin resistance. Mol Cell, 1998, 1(4)：619－625.
	3　Howard JK, Flier JS. Attenuation of leptin and insulin signaling by SOCS proteins. Trends Endocrinol Metab, 2006, 17(9)：365－371.
	4　Nakanishi T, Li R, Liu Z, et al. Sexual dimorphism in relationship of serum leptin and relative weight for the standard in normal－weight, but not in overweight, children as well as adolescents. Eur J Clin Nutr, 2001, 55(11)：989－993.
	5　Jin L, Zhang S, Burguera BG, et al. Leptin and leptin receptor expression in rat and mouse pituitary cells. Endocrinology, 2000, 141(1)：333－339.
	6　Funahashi H, Yada T, Suzuki R, et al. Distribution, function, and properties of leptin receptors in the brain. Int Rev Cytol, 2003, 224：1－27.
	7　Bjorbaek C, Kahn BB. Leptin signaling in the central nervous system and the periphery. Recent Prog Horm Res, 2004, 59: 305－331.
	8　Peiser C, McGregor GP, Lang RE. Leptin receptor expression and suppressor of cytokine signaling transcript levels in high－fat－fed rats. Life Sci, 2000, 67(24): 2971－2981.
	9　Howard JK，Cave BJ, Oksanen LJ, et al. Enhanced leptin sensitivity and attenuation of diet－induced obesity in mice with haploin sufficiency of SOCS3. Nat Med, 2004, 10(7)：734－738.
	10　Mori H, Hanada R, Hanada T, et al. SOCS3 deficiency in the brain elevates lpetin sensitivity and confers resistance to diet－induced obesity. Nat Med, 2004, 10(7)：739－743.
	11　Kievit P, Howard JK, Badman MK. Enhanced leptin sensitivity and improved glucose homeostasis in mice lacking suppressor of cytokine signaling－3 in POMC－expressing cells. Cell Metab, 2006, 4(2)：123－132.

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Study on the Expression of Suppressors-of-Cytokine-Signaling 3 mRNA in Hypothalamus and Liver in Obese Rats Fed With High-Fat Diet

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Study on the Expression of Suppressors-of-Cytokine-Signaling 3 mRNA in Hypothalamus and Liver in Obese Rats Fed With High-Fat Diet