title: Effects of beta-hydroxy-beta-methylbutyrate (HMB) on the expression of ubiquitin ligases, protein synthesis pathways and contractile function in extensor digitorum longus (EDL) of fed and fasting rats.
abstract: Beta-hydroxy-beta-methylbutyrate (HMB), a leucine metabolite, enhances the gain of skeletal muscle mass by increasing protein synthesis or attenuating protein degradation or both. The aims of this study were to investigate the effect of HMB on molecular factors controlling skeletal muscle protein synthesis and degradation, as well as muscle contractile function, in fed and fasted conditions. Wistar rats were supplied daily with HMB (320 mg/kg body weight diluted in NaCl-0.9%) or vehicle only (control) by gavage for 28 days. After this period, some of the animals were subjected to a 24-h fasting, while others remained in the fed condition. The EDL muscle was then removed, weighed and used to evaluate the genes and proteins involved in protein synthesis (AKT/4E-BP1/S6) and degradation (Fbxo32 and Trim63). A sub-set of rats were used to measure in vivo muscle contractile function. HMB supplementation increased AKT phosphorylation during fasting (three-fold). In the fed condition, no differences were detected in atrogenes expression between control and HMB supplemented group; however, HMB supplementation did attenuate the fasting-induced increase in their expression levels. Fasting animals receiving HMB showed improved sustained tetanic contraction times (one-fold) and an increased muscle to tibia length ratio (1.3-fold), without any cross-sectional area changes. These results suggest that HMB supplementation under fasting conditions increases AKT phosphorylation and attenuates the increased of atrogenes expression, followed by a functional improvement and gain of skeletal muscle weight, suggesting that HMB protects skeletal muscle against the deleterious effects of fasting.
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, 05508-900, Brazil. fredgerlinger@gmail.com.|Prédio Biomédicas I-Cidade Universitária-Butantã, Av. Prof. Lineu Prestes 1524, São Paulo, SP, CEP 05508-900, Brazil. fredgerlinger@gmail.com.
authors.forename: Frederico
authors.identifier: http://orcid.org/0000-0002-2150-0384
authors.initials: F
authors.lastname: Gerlinger-Romero
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, 05508-900, Brazil.|Exercise Metabolism Research Group, Department of Sports, Center of Physical Education and Sports, Federal University of Espirito Santo, Vitoria, Brazil.
authors.forename: Lucas
authors.initials: L
authors.lastname: Guimarães-Ferreira
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, 05508-900, Brazil.
authors.forename: Caio Yogi
authors.initials: CY
authors.lastname: Yonamine
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, 05508-900, Brazil.
authors.forename: Rafael Barrera
authors.initials: RB
authors.lastname: Salgueiro
authors.affiliation: Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, São Paulo, 05508-900, Brazil.
authors.forename: Maria Tereza
authors.initials: MT
authors.lastname: Nunes
mesh_terms: D000818:Animals; D002352:Carrier Proteins / Q000378:metabolism; D005215:Fasting / Q000378:metabolism; D007930:Leucine / Q000378:metabolism; D008025:Ligases / Q000378:metabolism*; D008297:Male; D009119:Muscle Contraction / Q000187:drug effects; D018482:Muscle, Skeletal / Q000187:drug effects / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D051381:Rats; D017208:Rats, Wistar; D025801:Ubiquitin / Q000378:metabolism*; D014631:Valerates / Q000494:pharmacology*
chemical_list: D002352:Carrier Proteins; D025801:Ubiquitin; D014631:Valerates; C004961:beta-hydroxyisovaleric acid; D008025:Ligases; D007930:Leucine
keywords: EDL; HMB; Muscle contraction; Protein degradation; Protein synthesis