Low leptin mRNA level in adipose tissue and normoleptinemia in experimental chronic renal failure.

J Swierczynski, J Korczynska, M Szolkiewicz, J Karbowska, Z Kochan, T Nieweglowski, E Kusiak, B Rutkowski
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引用次数: 26

Abstract

Background: Anorexia and weight loss frequently accompany chronic renal failure (CRF). Although multiple metabolic changes occur during CRF, a bulk of evidence indicates that the decrease in caloric intake plays a major role in CRF-induced weight loss. Recently, it has been suggested that elevated plasma leptin concentrations could contribute to anorexia and to downregulation of leptin gene expression in CRF patients. However, in some CRF patients, plasma leptin concentrations have been found to be lower than one could expect. Thus we assumed that inhibition of leptin synthesis plays an important role in the regulation of plasma leptin concentrations in CRF patients.

Methods: To test this assumption, the leptin mRNA level in rat white adipose tissue from ad-libitum-fed control (sham operated), pair-fed control (sham operated) and rats with experimentally induced CRF has been measured by Northern blotting analysis. In addition, serum leptin concentration (by radioimmunoassay) was determined in all three groups of animals.

Results: The results of the present study indicate that in experimental CRF the leptin mRNA level is decreased by about 50% as compared to the sham-operated animals (ad-libitum-fed and pair-fed controls). The mean serum leptin concentration in CRF rats was essentially similar to the leptin concentration in sham-operated ones.

Conclusion: The data obtained suggest that in CRF animals the serum leptin concentration might be affected not only by the decrease in leptin removal in the kidney, but also by the decrease in leptin secretion from adipose tissue. Furthermore, the results of the study suggest that leptin may be only one of many factors involved in the pathogenesis of malnutrition associated with CRF.

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实验性慢性肾功能衰竭脂肪组织瘦素mRNA水平低与正常瘦素血症的关系。
背景:厌食症和体重减轻经常伴随慢性肾功能衰竭(CRF)。尽管在CRF期间会发生多种代谢变化,但大量证据表明,热量摄入的减少在CRF诱导的体重减轻中起主要作用。最近,有研究表明血浆瘦素浓度升高可能导致厌食症和CRF患者瘦素基因表达下调。然而,在一些慢性肾功能衰竭患者中,发现血浆瘦素浓度低于预期。因此,我们认为抑制瘦素合成在CRF患者血浆瘦素浓度的调节中起重要作用。方法:为了验证这一假设,采用Northern blotting分析方法,测定了自由喂养对照组(假手术)、成对喂养对照组(假手术)和实验性诱导CRF大鼠白色脂肪组织中瘦素mRNA的水平。此外,用放射免疫法测定了三组动物的血清瘦素浓度。结果:本研究结果表明,与假手术动物(自由喂养和配对喂养对照)相比,实验CRF中瘦素mRNA水平下降了约50%。CRF大鼠的平均血清瘦素浓度与假手术大鼠基本相似。结论:CRF动物血清瘦素浓度不仅受到肾脏中瘦素去除量减少的影响,还受到脂肪组织中瘦素分泌量减少的影响。此外,研究结果表明,瘦素可能只是参与CRF相关营养不良发病机制的众多因素之一。
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