PMID- 34081111 OWN - NLM STAT- MEDLINE DCOM- 20211001 LR - 20230214 IS - 1938-3207 (Electronic) IS - 0002-9165 (Linking) VI - 114 IP - 3 DP - 2021 Sep 1 TI - Anabolic effects of oral leucine-rich protein with and without beta-hydroxybutyrate on muscle protein metabolism in a novel clinical model of systemic inflammation-a randomized crossover trial. PG - 1159-1172 LID - 10.1093/ajcn/nqab148 [doi] AB - BACKGROUND: beta-lactoglobulin (BLG) stimulates muscle protein synthesis and beta-hydroxybutyrate (BHB) inhibits muscle breakdown. Whether combining the 2 can additively attenuate disease-induced muscle loss is unknown. OBJECTIVE: Based on previous observations of anticatabolic effects of protein and ketone bodies during inflammation, and using a novel model combining ongoing systemic inflammation, fasting, and immobilization, we tested whether the anticatabolic muscle response to oral amino acids is altered compared with control conditions, as well as whether coadministration of oral BHB and BLG further improves the muscle anabolic response. Muscle net balance (NBphe) was the primary outcome and intramyocellular signals were assessed. METHODS: In a randomized crossover design, 8 young men underwent either preconditioning with LPS (prestudy day: 1 ng/kg, study day: 0.5 ng/kg) combined with a 36-h fast and bed rest to mimic catabolic inflammatory disease (CAT) or an overnight fast (control [CTR]) prior to isocaloric nutritional interventions on 3 occasions separated by approximately 6 wk (range 42 to 83 d). RESULTS: NBphe increased similarly upon all conditions (interaction P = 0.65). From comparable baseline rates, both Rdphe [muscle synthesis, median ratio (95% CI): 0.44 (0.23, 0.86) P = 0.017] and Raphe [muscle breakdown, median ratio (95% CI): 0.46 (0.27, 0.78) P = 0.005] decreased following BHB + BLG compared with BLG. BLG increased Rdphe more under CAT conditions compared with CTR (interaction P = 0.02). CAT increased inflammation, energy expenditure, and lipid oxidation and decreased Rdphe and anabolic signaling [mammalian target of rapamycin (mTOR) and eukaryotic translation initiation factor 4E-binding protein 1 (4EPB1) phosphorylation]. CONCLUSION: In contrast to our initial hypothesis, NBphe increased similarly following BLG during CAT and CTR conditions; CAT however, specifically stimulated the BLG-mediated increase in protein synthesis, whereas BHB coadministration did not affect NBphe, but distinctly dampened the BLG-induced increase in muscle amino acid fluxes thereby liberating circulating amino acids for anabolic actions elsewhere. CI - (c) The Author(s) 2021. Published by Oxford University Press on behalf of the American Society for Nutrition. FAU - Mose, M AU - Mose M AUID- ORCID: 0000-0003-2394-8067 AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Brodersen, K AU - Brodersen K AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Surgery, Viborg Regional Hospital, Viborg, Denmark. FAU - Rittig, N AU - Rittig N AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Schmidt, J AU - Schmidt J AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. FAU - Jessen, N AU - Jessen N AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Clinical Pharmacology, Aarhus University Hospital, Aarhus, Denmark. AD - Department of Biomedicine, Aarhus University, Aarhus, Denmark. FAU - Mikkelsen, U R AU - Mikkelsen UR AD - Arla Foods Ingredients Group P/S, Viby, Denmark. FAU - Jorgensen, J O L AU - Jorgensen JOL AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. FAU - Moller, N AU - Moller N AD - Department of Endocrinology and Internal Medicine, Aarhus University Hospital, Aarhus, Denmark. AD - Steno Diabetes Center Aarhus, Aarhus University Hospital, Aarhus, Denmark. LA - eng PT - Journal Article PT - Randomized Controlled Trial PT - Research Support, Non-U.S. Gov't PL - United States TA - Am J Clin Nutr JT - The American journal of clinical nutrition JID - 0376027 RN - 0 (Lactoglobulins) RN - 0 (Lipopolysaccharides) RN - 0 (Muscle Proteins) RN - TZP1275679 (3-Hydroxybutyric Acid) SB - IM MH - 3-Hydroxybutyric Acid/administration & dosage/*pharmacology MH - Adult MH - Cross-Over Studies MH - Energy Metabolism MH - Gene Expression Regulation/drug effects MH - Humans MH - Inflammation/*chemically induced MH - Lactoglobulins/administration & dosage/*pharmacology MH - *Lipid Peroxidation MH - Lipopolysaccharides/toxicity MH - Male MH - Muscle Proteins/genetics/*metabolism MH - Signal Transduction MH - Young Adult OTO - NOTNLM OT - dairy protein OT - endotoxemia OT - fasting OT - immobilization OT - metabolism OT - muscle signaling OT - skeletal muscle OT - beta-hydroxybutyrate EDAT- 2021/06/04 06:00 MHDA- 2021/10/02 06:00 CRDT- 2021/06/03 12:24 PHST- 2020/08/28 00:00 [received] PHST- 2021/04/09 00:00 [accepted] PHST- 2021/06/04 06:00 [pubmed] PHST- 2021/10/02 06:00 [medline] PHST- 2021/06/03 12:24 [entrez] AID - S0002-9165(22)00439-7 [pii] AID - 10.1093/ajcn/nqab148 [doi] PST - ppublish SO - Am J Clin Nutr. 2021 Sep 1;114(3):1159-1172. doi: 10.1093/ajcn/nqab148.