Are plasma concentrations of leptin and carnitineinterrelated in haemodialysis patients?

Franciszek Kokot1, Wieslawa Lysiak-Szydlowska2, Marcin Adamczak1, Jerzy Chudek1, Witold Ignacy1, Boleslaw Rutkowski3, Rafal Ficek1 and Andrzej Wiecek1

1 Department of Nephrology, Endocrinology and Metabolic Diseases, Silesian University Medical School, Katowice, 2 Department of Clinical Nutrition and 3 Department of Nephrology, Medical University of Gdansk, Poland

Sir,

Recently a novel form of lipolysis in adipocytes stimulated by leptin was described in Zucker diabetic rats [1]. In this form of lipolysis, leptin increases release of glycerol without the parallel proportional rise in free fatty acids. Carnitine is a coenzyme of carnitine palmitoyl transferase-1, which controls the transport of long-chain fatty acids into mitochondria where oxidation of fatty acids takes place [2]. An upregulation of carnitine palmitoyl transferase-1 and acyl CoA oxidase mRNA was shown in adipocytes stimulated by leptin [1].

Uraemic patients treated by intermittent haemodialysis have elevated plasma leptin concentrations, compared with healthy subjects [3]. In these patients, increased lipolysis induced by leptin and higher expression of the carnitine palmitoyl transferase-1 in adipocytes can be anticipated.

This study aimed to investigate the relationship between plasma carnitine and leptin concentration. Seventy chronic haemodialysis patients (35 males, 35 females; mean age 46±2 years; mean duration of haemodialysis replacement therapy 36±6 months) were enrolled in the study. Blood samples were withdrawn from fasting subjects in the morning before a subsequent haemodialysis session. The following parameters were estimated: plasma leptin, total carnitine (TC), free carnitine (FC), and serum cholesterol and triglyceride concentrations. Plasma leptin concentrations were estimated by RIA method (Linco Research), and TC and FC using the enzymatic method of Cederblad et al. [4], modified by Salek et al. [5]. Body composition (total fat mass (TFM) and total lean mass (TLM)) was evaluated by DEXA (Lunar Inc.). Statistical analysis was carried out with Statistica-PL Software 6.0. All values are expressed as mean±SEM. Mann–Whitney U-test was used for subgroups comparison and the Kendall-tau correlation coefficient was calculated.

The subjects were divided into three subgroups, taking into account the magnitude of TFM: the first subgroup comprised 22 patients with a TFM<=10 kg, the second one 27 patients with a TFM>10–20 kg, and the third subgroup 21 patients with TFM>=20 kg. Results are shown in Table 1Go. As can be seen in Table 1Go the groups of patients differed significantly with respect to body mass index (BMI), TFM, plasma leptin, and serum triglyceride and cholesterol concentrations. A tendency to higher plasma carnitine concentration (total and free) was observed in patients with higher TFM. As expected there was a strong positive correlation between plasma leptin concentration and TFM (Table 2Go). A significant positive correlation was also noted between total plasma carnitine and leptin concentration, between plasma carnitine (total and free) and TFM, and between plasma carnitine (total and free) and TLM. Statistical analysis revealed the presence of significant positive correlations between serum triglycerides and plasma leptin and TFM respectively, and between serum cholesterol and plasma leptin and TFM respectively.


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Table 1. Parameters of body composition and plasma concentrations of leptin and carnitine and serum lipids concentrations in patients with a total fat mass <=10 kg (group 1), between >10 kg and 20 kg (group 2) and >=20 kg (group 3)

 

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Table 2. Correlations coefficients (Kendal tau test) between the following parameters: total fat mass (TFM), total lean mass (TLM), plasma leptin, total carnitine (TC), free carnitine (FC) and serum triglycerides (Trigl.) and cholesterol (Chol.) concentrations

 
Plasma carnitine concentration is presumed to be a marker of nutritional status in haemodialysis patients. The values of plasma carnitine (total and free) observed in the uraemic patients of the present study are in line with results of those studies in which deficiency of this compound in the majority of haemodialysed patients (at least in plasma) was not confirmed [6,7]. Interestingly we found a positive correlation between plasma carnitine and leptin. Leptin is a marker of body fat stores both in healthy subjects and patients on renal replacement therapy [3]. Based on these data it can be suggested that both leptin and carnitine are markers of nutritional well-being in these patients.

There is no doubt that increased lipolysis induced by high plasma leptin concentration enhances the requirement for carnitine. However we did not observe carnitine deficiency in obese hyperleptinaemic patients. On the contrary, in such patients plasma carnitine concentrations were higher in patients with a higher TFM. As leptin increases lipolysis and fatty acid oxidation in adipocytes and enhances energy expenditure [8], rather lower TFM may be expected in haemodialysed patients. As the contrary was found, it seems highly likely that elevated plasma leptin levels in haemodialysed patients are dependent not only upon TFM but also upon other factors such as increased synthesis, reduced degradation, or both.

From the results obtained in this study it follows that the interrelations between carnitine, leptin, and lipolysis are complex. Nevertheless, both leptin and carnitine appear to be markers of nutritional well-being in haemodialysis patients. Moreover, they are pathophysiologically associated with each other, although this association was relatively weak.

Acknowledgments

Marcin Adamczak was partially supported by the Foundation for Polish Science (scholarship for young researchers).

References

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  2. Hoople C. The physiological role of carnitine. In: Ferrari R, DiMauro S, Sherwood G. eds. L-Carnitine and Its Role in Medicine: from Function to Therapy. Academic Press, London, 1992; 5–17
  3. Stenvinkel P. Leptin—a hormone of definite interest for the nephrologist. Nephrol Dial Transplant1998; 13: 1099–1101[Free Full Text]
  4. Cederblad G, Harper P, Lingren K. Spectrophotometry of carnitine in biological fluids and tissue with Cobas Bio centrifugal analyzer. Clin Chem1986; 32: 342–346[Abstract/Free Full Text]
  5. Salek J, Mierzewski P, Wsewicz M, Uszycka-Karcz M, Lysiak-Szydlowska W. Carnitine in serum and urine. Monitoring of L-carnitine therapy. Diagn Lab1989; 25: 109–118
  6. Moorthy AV, Rosenblum M, Raja R, Shuk AL. A comparison of plasma and muscle carnitine levels in patients on peritoneal or hemodialysis for chronic renal failure. Am J Nephrol1983; 3: 205–208[ISI][Medline]
  7. Debska-Slizien A, Kawecka A, Wojnarowski K et al. Correlation between plasma carnitine, muscle carnitine and glycogen levels in maintance hemodialysis patients. Int J Artif Organs2000; 23: 90–96[ISI][Medline]
  8. Auwerx J, Staels B. Leptin. Lancet1998; 353: 737–742[ISI]




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