Effects of leucine and its metabolite β‐hydroxy‐β‐methylbutyrate on human skeletal muscle protein metabolism

Abstract

Key points The branched‐chain amino acid (BCAA) leucine acts as both a ‘trigger’ for the initiation of protein synthesis, and as a substrate for newly synthesized protein. As a BCAA, leucine can be metabolized within skeletal muscle, leaving open the possibility that leucine metabolites might possess anabolic properties. One metabolite in particular, β‐hydroxy‐β‐methylbutyrate (HMB), has shown positive effects on lean body mass and strength following exercise, and in disease‐related muscle wasting, yet its impact on acute human muscle protein turnover is undefined. We report here that HMB stimulates muscle protein synthesis to a similar extent to leucine. HMB was also found to decrease muscle protein breakdown. Our observation that HMB enhances muscle protein anabolism may partly (or wholly) underlie its pre‐defined anabolic/anti‐catabolic supplemental efficacy in humans. Abstract Maintenance of skeletal muscle mass is contingent upon the dynamic equilibrium (fasted losses–fed gains) in protein turnover. Of all nutrients, the single amino acid leucine (Leu) possesses the most marked anabolic characteristics in acting as a trigger element for the initiation of protein synthesis. While the mechanisms by which Leu is ‘sensed’ have been the subject of great scrutiny, as a branched‐chain amino acid, Leu can be catabolized within muscle, thus posing the possibility that metabolites of Leu could be involved in mediating the anabolic effect(s) of Leu. Our objective was to measure muscle protein anabolism in response to Leu and its metabolite HMB. Using [1,2‐ 13 C 2 ]Leu and [ 2 H 5 ]phenylalanine tracers, and GC‐MS/GC‐C‐IRMS we studied the effect of HMB or Leu alone on MPS (by tracer incorporation into myofibrils), and for HMB we also measured muscle proteolysis (by arteriovenous (A–V) dilution). Orally consumed 3.42 g free‐acid (FA‐HMB) HMB (providing 2.42 g of pure HMB) exhibited rapid bioavailability in plasma and muscle and, similarly to 3.42 g Leu, stimulated muscle protein synthesis (MPS; HMB +70% vs . Leu +110%). While HMB and Leu both increased anabolic signalling (mechanistic target of rapamycin; mTOR), this was more pronounced with Leu (i.e. p70S6K1 signalling ≤90 min vs . ≤30 min for HMB). HMB consumption also attenuated muscle protein breakdown (MPB; −57%) in an insulin‐independent manner. We conclude that exogenous HMB induces acute muscle anabolism (increased MPS and reduced MPB) albeit perhaps via distinct, and/or additional mechanism(s) to Leu.

Shown for reading. Its publisher allows quoting it, not republishing it.

Cited by papers we hold 14

• LAT1 Protein Content Increases Following 12 Weeks of Resistance Exercise Training in Human Skeletal Muscle · 2021
  Not checked
• Branched-chain Amino Acids: Catabolism in Skeletal Muscle and Implications for Muscle and Whole-body Metabolism · 2021
  No notice
• The Anabolic Response to Plant-Based Protein Ingestion · 2021
  No notice
• Osteosarcopenia: epidemiology, diagnosis, and treatment—facts and numbers · 2020
  No notice
• Regulation of Skeletal Muscle Function by Amino Acids · 2020
  No notice
• The age-related loss of skeletal muscle mass and function: Measurement and physiology of muscle fibre atrophy and muscle fibre loss in humans · 2018
  No notice
• Branched-chain amino acids and muscle protein synthesis in humans: myth or reality? · 2017
  No notice
• The Role of Inflammation in Age-Related Sarcopenia · 2017
  No notice
• Periodized Nutrition for Athletes · 2017
  No notice
• Live strong and prosper: the importance of skeletal muscle strength for healthy ageing · 2016
  No notice
• Protein Consumption and the Elderly: What Is the Optimal Level of Intake? · 2016
  No notice
• Skeletal muscle homeostasis and plasticity in youth and ageing: impact of nutrition and exercise · 2015
  No notice
• A Brief Review of Critical Processes in Exercise-Induced Muscular Hypertrophy · 2014
  No notice
• Regulation of autophagy by amino acids and MTOR-dependent signal transduction · 2014
  No notice

Reads

A person counts once a day per paper. We keep no cookie and no address: a reader is a hash that changes every day. Any month under five reads shows no number.