Intermittent leucine pulses during continuous feeding alters novel components involved in skeletal muscle growth of neonatal pigs.

When neonatal pigs continuously fed formula are supplemented with leucine pulses, muscle protein synthesis and body weight gain are enhanced. To identify the responsible mechanisms, we combined plasma metabolomic analysis with transcriptome expression of the transcriptome and protein catabolic pathways in skeletal muscle. Piglets (n = 23, 7-day-old) were fed continuously a milk replacement formula via orogastric tube for 21 days with an additional parenteral infusion (800 µmol kg-1 h-1) of either leucine (LEU) or alanine (CON) for 1 h every 4 h. Plasma metabolites were measured by liquid chromatography-mass spectrometry. Gene and protein expression analyses of longissimus dorsi muscle were performed by RNA-seq and Western blot, respectively. Compared with CON, LEU pigs had increased plasma levels of leucine-derived metabolites, including 4-methyl-2-oxopentanoate, beta-hydroxyisovalerate, ß-hydroxyisovalerylcarnitine, and 3-methylglutaconate (P ≤ 0.05). Leucine pulses downregulated transcripts enriched in the Kyoto Encyclopedia of Genes and Genomes terms "spliceosome," "GAP junction," "endocytosis," "ECM-receptor interaction," and "DNA replication". Significant correlations were identified between metabolites derived from leucine catabolism and muscle genes involved in protein degradation, transcription and translation, and muscle maintenance and development (P ≤ 0.05). Further, leucine pulses decreased protein expression of autophagic markers and serine/threonine kinase 4, involved in muscle atrophy (P ≤ 0.01). In conclusion, results from our studies support the notion that leucine pulses during continuous enteral feeding enhance muscle mass gain in neonatal pigs by increasing protein synthetic activity and downregulating protein catabolic pathways through concerted responses in the transcriptome and metabolome.

Supplementation with Whey Protein, Omega-3 Fatty Acids and Polyphenols Combined with Electrical Muscle Stimulation Increases Muscle Strength in Elderly Adults with Limited Mobility: A Randomized Controlled Trial.

Age-related sarcopenia is a progressive and generalized skeletal muscle disorder associated with adverse outcomes. Herein, we evaluate the effects of a combination of electrical muscle stimulation (EMS) and a whey-based nutritional supplement (with or without polyphenols and fish oil-derived omega-3 fatty acids) on muscle function and size. Free-living elderly participants with mobility limitations were included in this study. They received 2 sessions of EMS per week and were randomly assigned to ingest an isocaloric beverage and capsules for 12 weeks: (1) carbohydrate + placebo capsules (CHO, n = 12), (2) whey protein isolate + placebo capsules (WPI, n = 15) and (3) whey protein isolate + bioactives (BIO) capsules containing omega-3 fatty acids, rutin, and curcumin (WPI + BIO, n = 10). The change in knee extension strength was significantly improved by 13% in the WPI + BIO group versus CHO on top of EMS, while WPI alone did not provide a significant benefit over CHO. On top of this, there was the largest improvement in gait speed (8%). The combination of EMS and this specific nutritional intervention could be considered as a new approach for the prevention of sarcopenia but more work is needed before this approach should be recommended. This trial was registered at the Japanese University Hospital Medical Information Network (UMIN) clinical trial registry (UMIN000008382).