Low Leptin mRNA Level in Adipose Tissue and Normoleptinemia in Experimental Chronic Renal Failure

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.

Differential Effect of Long-term Food Restriction on Fatty Acid Synthase and Leptin Gene Expression in Rat White Adipose Tissue

“…After electrophoretic fractionation, RNA was transferred overnight to a positively charged nylon membrane (Roche, Mannheim, Germany) by capillary blotting and fixed with UV light. Pre-hybridization and hybridization were performed as described recently [19,22,23].…”

Increased Rate of Cholesterologenesis - A Possible Cause of Hypercholesterolemia in Experimental Chronic Renal Failure in Rats

“…These results suggest that leptin plays an important role in regulation of plasma cholesterol concentration. We found that CRF decreases by about 50 % the leptin gene expression in white adipose tissue from rats [9]. Taking these results as a whole [9,19], one may conclude that an increased rate of cholesterologenesis in CRF rats could partly be a consequence of lower leptin gene expression.…”

“…We found that CRF decreases by about 50 % the leptin gene expression in white adipose tissue from rats [9]. Taking these results as a whole [9,19], one may conclude that an increased rate of cholesterologenesis in CRF rats could partly be a consequence of lower leptin gene expression. Slightly lower amounts of food intake by CRF rats cannot be responsible for the increase of HMG-CoA reductase NADPH-producing enzyme gene expression, since fasting or food restriction causes a decrease in these enzymes' activity [8,10,18].…”

“…The experiments were performed on male Wistar rats (n = 18: 9 rats were used for in vivo cholesterol biosynthesis; 9 animals were used for HMG-CoA mRNA level determination and enzymes assay) weighing approximately 240 g at the beginning of the investigation. The rats were anesthetized with thiopental (60 mg/kg b. w., intraperitoneally), after which chronic renal failure was induced by a two-stage subtotal (5/6) nephrectomy as described recently [9]. The control group (n = 20: 10 rats were used for in vivo cholesterol biosynthesis; 10 were used for mRNA and enzyme assay) was sham-operated.…”

Up-regulation of liver Pcsk9 gene expression as a possible cause of hypercholesterolemia in experimental chronic renal failure

“…Animals were kept in individual cages with free access to tap water, and with controlled lighting schedule (illuminated from 7 a.m to 7 p.m.). Experimental CRF was induced by two-stage (5/6) subtotal nephrectomy as described previously [ 23 ]. Average daily food intake was measured by the difference in weight between the amount of food provided and the amount remaining over a 1-day period.…”