Effect of beta-hydroxy-beta-methylbutyrate (HMB) on protein metabolism in whole body and in selected tissues

https://doi.org/10.1016/j.fct.2008.11.021Get rights and content

Abstract

Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite with protein anabolic effect. The aim of the study was to examine the role of exogenous HMB on leucine and protein metabolism in whole body and selected tissues.

Rats were administered by HMB (0.1 g/kg b.w.) or by saline. The parameters of whole-body protein metabolism were evaluated 24 h later using l-[1-14C]leucine and l-[3,4,5-3H]phenylalanine. Changes in proteasome dependent proteolysis and protein synthesis were determined according the “chymotrypsin-like” enzyme activity and labeled leucine and phenylalanine incorporation into the protein.

A decrease in leucine clearance and whole-body protein turnover (i.e., a decrease in whole-body proteolysis and protein synthesis) was observed in HMB treated rats. Proteasome-dependent proteolysis decreased significantly in skeletal muscle, changes in heart, liver, jejunum, colon, kidney, and spleen were insignificant. Decrease in protein synthesis was observed in the heart, colon, kidney, and spleen, while an increase was observed in the liver. There were no significant changes in leucine oxidation.

We conclude that protein anabolic effect of HMB in skeletal muscle is related to inhibition of proteolysis in proteasome. Alterations in protein synthesis in visceral tissues may affect several important functions and the metabolic status of the whole body.

Introduction

Beta-hydroxy-beta-methylbutyrate (HMB) is a leucine metabolite (Fig. 1) with protein anabolic effect which may be employed in treatment of proteocatabolic illness or to increase muscle mass and/or muscle strength during exercise. A favorable effect of exogenous HMB on protein balance has been reported in cancer (May et al., 2002, Smith et al., 2005) and in resistance exercise (Jówko et al., 2001, Nissen and Sharp, 2003). Unfortunately, the results of controlled trials evaluating the effect of HMB alone or in mixture with other dietary supplements in reversing cachexia in proteocatabolic illness are not conclusive (May et al., 2002, Marcora et al., 2005, Clark et al., 2000) and further studies are necessary to confirm beneficial effect of HMB.

The most of the available data concerning the effect of HMB is related to skeletal muscle and there is the absence of relevant information about changes in whole-body protein metabolism and in specific tissues which could significantly affect protein balance and outcome of the illness.

It seems, that HMB is responsible partly for well-known protein anabolic effect of leucine. Neither other two branched-chain amino acids (BCAAs), valine or isoleucine, nor other amino acid and/or their metabolites show this unique feature (De Bandt and Cynober, 2006). However, there is no study evaluating the effect of exogenous HMB on BCAA metabolism, although phenomena of metabolic antagonism exists among BCAAs.

The aim of this study was to examine the effect of HMB administration on leucine and protein metabolism in whole body and to estimate changes in protein synthesis and proteolysis in selected tissues. Two tracers (l-[1-14C]leucine and l-[3,4,5-3H]phenylalanine) were used to test the possible effect of interference of HMB and leucine metabolism and to avoid its effect on interpretation of the obtained results.

Section snippets

Animals and material

Male Wistar rats (BioTest, Konarovice, CR) weighing about 260 g, were housed in standardized cages in quarters with controlled temperature and a 12-h light–dark cycle and received Velaz-Altromin 1320 laboratory chow and drinking water ad libitum. All procedures involving animals were performed according to guidelines set by the Institutional Animal Use and Care Committee of Charles University. l-[1-14C]leucine was purchased from Amersham (Buckinghamshire, UK), [14C]bicarbonate was from Du

Blood plasma

HMB treatment induced a significant increase in total cholesterol in blood plasma. There were no differences in HDL and LDL cholesterol, atherogenity index, triglycerides, glucose, and urea levels (Table 1).

Parameters of whole-body amino acid and protein metabolism

Using infusion of l-[1-14C]leucine was shown that HMB treatment induced a significant decrease in whole-body protein turnover, i.e. a decrease both in whole-body proteolysis and protein synthesis (Table 2). In addition, a decrease in leucine clearance was observed. The effect on protein

Discussion

Several studies demonstrated that supplemental HMB is well tolerated and has no adverse effects (Baxter et al., 2005). Significant increase in blood cholesterol is a clear evidence of metabolic changes induced by HMB administration in our study. The observation is in agreement with presumption that HMB is metabolized to HMG-CoA and is used for de novo synthesis of cholesterol in certain tissues. It should be noted, that this observation is in discrepancy with findings of Nissen and Abumrad

Conflict of interest statement

The authors declare that there are no conflicts of interest.

Acknowledgments

We are grateful for technical support of I. Altmannova, H. Buzkova, L. Kriesfalusyova, D. Jezkova, and R. Rysava. Many thanks to dr. Hana Skalska for help with statistical analysis. The study was supported by Research Project MSM0021620820.

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