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 Gdask, 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 Blood samples were withdrawn from fasting subjects in the morning before a subsequent haemodialysis session.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. MannWhitney 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 TFM10 kg, the second one 27 patients with a TFM>1020 kg, and the third subgroup 21 patients with TFM
20 kg. Results are shown in Table 1
. As can be seen in Table 1
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 2
). 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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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