Whole-body and forearm muscle protein metabolism in patients with acromegaly before and after treatment

TY - JOUR

T1 - Whole-body and forearm muscle protein metabolism in patients with acromegaly before and after treatment

AU - Arlien-Søborg, Mai C

AU - Dal, Jakob

AU - Madsen, Michael Alle

AU - Høgild, Morten Lyng

AU - Pedersen, Steen B

AU - Jessen, Niels

AU - Jørgensen, Jens O L

AU - Møller, Niels

N1 - © The Author(s) 2023. Published by Oxford University Press on behalf of the Endocrine Society. All rights reserved. For permissions, please e-mail: [email protected].

PY - 2023/9

Y1 - 2023/9

N2 - BACKGROUND: Active acromegaly is characterized by increased lean body mass but the mechanisms underlying the protein anabolic effect are unclear.AIM: To study if active acromegaly induces reversible changes in whole-body and skeletal muscle protein kinetics.PATIENTS AND METHODS: Eighteen patients with acromegaly were investigated before and 47 ± 10 weeks after disease control by surgery (n = 8) and/or medical treatment (n = 10). Labelled phenylalanine and tyrosine tracers were employed to assess whole-body and regional forearm muscle protein kinetics. Intramyocellular protein signaling was assessed in skeletal muscle biopsies, and whole-body DXA scan and indirect calorimetry assessed lean body mass (LBM) and resting energy expenditure, respectively.RESULTS: Disease control induced a 7% decrease in lean body mass (p < 0.000) and a 14% decrease in LBM-adjusted energy expenditure. Whole-body phenylalanine breakdown decreased after disease control (p = 0.005) accompanied by a decrease in the degradation of phenylalanine to tyrosine (p= 0.005) and a decrease in whole-body phenylalanine synthesis (p = 0.030). Skeletal muscle protein synthesis tended to decrease after disease control (p = 0.122), whereas the muscle protein breakdown (p = 0.437) and muscle protein loss were unaltered (p = 0.371). ULK1 phosphorylation, an activator of protein breakdown, increased after disease control (p= 0.042).CONCLUSIONS: Active acromegaly represents a reversible high flux state in which both whole-body protein breakdown and synthesis are increased, whereas forearm muscle protein kinetics are unaltered. Future studies are needed to decipher the link between protein kinetics and the structure and function of the associated GH-induced increase in lean body mass.

AB - BACKGROUND: Active acromegaly is characterized by increased lean body mass but the mechanisms underlying the protein anabolic effect are unclear.AIM: To study if active acromegaly induces reversible changes in whole-body and skeletal muscle protein kinetics.PATIENTS AND METHODS: Eighteen patients with acromegaly were investigated before and 47 ± 10 weeks after disease control by surgery (n = 8) and/or medical treatment (n = 10). Labelled phenylalanine and tyrosine tracers were employed to assess whole-body and regional forearm muscle protein kinetics. Intramyocellular protein signaling was assessed in skeletal muscle biopsies, and whole-body DXA scan and indirect calorimetry assessed lean body mass (LBM) and resting energy expenditure, respectively.RESULTS: Disease control induced a 7% decrease in lean body mass (p < 0.000) and a 14% decrease in LBM-adjusted energy expenditure. Whole-body phenylalanine breakdown decreased after disease control (p = 0.005) accompanied by a decrease in the degradation of phenylalanine to tyrosine (p= 0.005) and a decrease in whole-body phenylalanine synthesis (p = 0.030). Skeletal muscle protein synthesis tended to decrease after disease control (p = 0.122), whereas the muscle protein breakdown (p = 0.437) and muscle protein loss were unaltered (p = 0.371). ULK1 phosphorylation, an activator of protein breakdown, increased after disease control (p= 0.042).CONCLUSIONS: Active acromegaly represents a reversible high flux state in which both whole-body protein breakdown and synthesis are increased, whereas forearm muscle protein kinetics are unaltered. Future studies are needed to decipher the link between protein kinetics and the structure and function of the associated GH-induced increase in lean body mass.

KW - acromegaly

KW - body composition

KW - growth hormone

KW - protein kinetics

KW - protein metabolism

KW - Energy Metabolism/physiology

KW - Muscle Proteins/metabolism

KW - Tyrosine

KW - Phenylalanine

KW - Humans

KW - Muscle, Skeletal/metabolism

KW - Body Composition/physiology

KW - Forearm

KW - Acromegaly/therapy

UR - http://www.scopus.com/inward/record.url?scp=85168316045&partnerID=8YFLogxK

U2 - 10.1210/clinem/dgad190

DO - 10.1210/clinem/dgad190

M3 - Journal article

C2 - 37036819

SN - 0021-972X

VL - 108

SP - e671-e678

JO - The Journal of Clinical Endocrinology & Metabolism

JF - The Journal of Clinical Endocrinology & Metabolism

IS - 9

ER -