The leucine metabolite 3‐hydroxy‐3‐methylbutyrate (HMB) modifies protein turnover in muscles of laboratory rats and domestic chickensin vitro

Abstract

This study was conducted to assess the in vitro effects of leucine and 3‐hydroxy‐3‐methylbutyrate (HMB) on protein synthesis and degradation in isolated rat and chick muscles. Isolated muscles — extensor digitorum longus (EDL) and soleus (S) in rats and EDL and tibialis anterior (TA) in chicks — were taken out intact and incubated in Krebs—Henseleit buffer with [14C]phenylalanine. Protein synthesis was then determined by measuring [14C]phenylalanine incorporation into protein and protein breakdown was estimated by net release of tyrosine from muscle proteins. In all muscles investigated leucine stimulated protein synthesis (average 20%; p < 0.05 versus control) but only slightly reduced proteolysis (average 8%, NS). In contrast, HMB had no significant effect on protein synthesis but consistently decreased protein degradation in the range from −29% (p < 0.01 versus control) in rat extensor digitorus longus to −5% (NS) in rat soleus muscles. HMB appeared to suppress protein degradation more in white muscle fibres than in red muscle fibres (at least in the rat). These data support observations in humans indicating that HMB decreases muscle proteolysis. It is suggested that metabolism of leucine to HMB could be responsible for the reported suppressive effects of leucine on protein breakdown.

Dietary supplementation of β‐hydroxy‐β‐methylbutyrate in animals – a review

“…Metabolic activity of the branched‐chain amino acid leucine and its metabolite HMB includes regulation of skeletal muscle protein turnover. This hypothesis has been confirmed in numerous in vivo and in vitro studies (Ostaszewski et al., ; Wilkinson et al., ).…”

“…In a trial undertaken with isolated rat and chick muscle, Ostaszewski et al. () indicated depression of proteolysis, but no significant effect on protein synthesis. When used in an experimental model of cancer‐induced weight loss in rats, HMB has been shown to attenuate protein degradation by regulating an increase in components of the ubiquitin–proteasome proteolytic pathway, an energy‐dependent proteolytic system that degrades intracellular proteins.…”

Influence of feeding the leucine metaboliteβ-hydroxy-β-methylbutyrate (HMB) on the non-specific cellular and humoral defence mechanisms of rainbow trout (Oncorhynchus mykiss)

“…HMB can then be converted to cytosolic β ‐hydroxy‐ β ‐methylglutaryl‐CoA and ultimately used as a precursor for cholesterol synthesis (Bloch et al, 1954; Adamson and Greenberg, 1957). It has been proposed that HMB is the leucine metabolite responsible for the effects of leucine on protein breakdown (Ostaszewski et al, 2000). Decreased protein breakdown and muscle damage was also previously shown in exercising humans (Nissen et al, 1996).…”

Atualizações sobre beta-hidroxi-beta-metilbutirato: suplementação e efeitos sobre o catabolismo de proteínas

“…Isto sugeriu, fortemente, que o efeito da leucina sobre a degradação protéica é mediado por algum metabólito. Um metabólito da leucina, candidato a promotor do efeito inibitório sobre o catabolismo protéico, é o β-hidroxi-β-metilbutirato (HMB) ao lado do α-ceto--isocaproato (CIC ou KIC) 9,10 . Ostaszewski et al 9 incubaram músculos de aves e ratos na presença de HMB e encontraram aumento da síntese protéica em 20% e redução do catabolismo protéico em, aproximadamente, 80%.…”

“…Um metabólito da leucina, candidato a promotor do efeito inibitório sobre o catabolismo protéico, é o β-hidroxi-β-metilbutirato (HMB) ao lado do α-ceto--isocaproato (CIC ou KIC) 9,10 . Ostaszewski et al 9 incubaram músculos de aves e ratos na presença de HMB e encontraram aumento da síntese protéica em 20% e redução do catabolismo protéico em, aproximadamente, 80%. Alguns autores propõem que, em situações de estresse, tanto animais quanto humanos não sintetizam quantidades de HMB necessárias para suprir a demanda tecidual 11 .…”