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

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.