Skeletal muscle protein turnover responses to parenteral nutrition in patients with alcoholic liver cirrhosis and sarcopenia

Am J Physiol Gastrointest Liver Physiol. 2023 Aug 1;325(2):G174-G183. doi: 10.1152/ajpgi.00242.2022. Epub 2023 Jun 20.

Abstract

Alcoholic liver cirrhosis (ALC) is accompanied by sarcopenia. The aim of this study was to investigate the acute effects of balanced parenteral nutrition (PN) on skeletal muscle protein turnover in ALC. Eight male patients with ALC and seven age- and sex-matched healthy controls were studied for 3 h of fasting followed by 3 h of intravenous PN (SmofKabiven 1,206 mL: amino acid = 38 g, carbohydrates = 85 g, and fat = 34 g) 4 mL/kg/h. We measured leg blood flow and sampled paired femoral arteriovenous concentrations and quadriceps muscle biopsies while providing a primed continuous infusion of [ring-2d5]-phenylalanine to quantify muscle protein synthesis and breakdown. Patients with ALC exhibited shorter 6-min walking distance (ALC: 487 ± 38 vs. controls: 722 ± 14 m, P < 0.05), lower hand-grip strength (ALC: 34 ± 2 vs. controls: 52 ± 2 kg, P < 0.05), and computed tomography (CT)-verified leg muscle loss (ALC: 5,922 ± 246 vs. controls: 8,110 ± 345 mm2, P < 0.05). Net leg muscle phenylalanine uptake changed from negative (muscle loss) during fasting to positive (muscle gain) in response to PN (ALC: -0.18 ± +0.01 vs. 0.24 ± 0.03 µmol/kg muscle·min-1; P < 0.001 and controls: -0.15 ± 0.01 vs. 0.09 ± 0.01 µmol/kg muscle·min-1; P < 0.001) but with higher net muscle phenylalanine uptake in ALC than controls (P < 0.001). Insulin concentrations were substantially higher in patients with ALC during PN. Our results suggest a higher net muscle phenylalanine uptake during a single infusion of PN in stable patients with ALC with sarcopenia compared with healthy controls.NEW & NOTEWORTHY Muscle protein turnover responses to parenteral nutritional (PN) supplementation have not previously been studied in stable alcoholic liver cirrhosis (ALC). We applied stable isotope tracers of amino acids to directly quantify net muscle protein turnover responses to PN in sarcopenic males with ALC and healthy controls. We found a higher net muscle protein gain in ALC during PN, thereby providing the physiological rationale for future clinical trials of PN as a potential countermeasure to sarcopenia.

Keywords: isotope labeling; liver cirrhosis; muscular atrophy; nutrition therapy; sarcopenia.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acids / metabolism
  • Case-Control Studies
  • Humans
  • Liver Cirrhosis / metabolism
  • Liver Cirrhosis, Alcoholic / metabolism
  • Liver Cirrhosis, Alcoholic / therapy
  • Male
  • Muscle Proteins / metabolism
  • Muscle Proteins / pharmacology
  • Muscle, Skeletal* / metabolism
  • Parenteral Nutrition*
  • Phenylalanine
  • Sarcopenia* / complications

Substances

  • Amino Acids
  • Muscle Proteins
  • Phenylalanine

Associated data

  • figshare/10.6084/m9.figshare.21311430