Click here to close
Hello! We notice that you are using Internet Explorer, which is not supported by Xenbase and may cause the site to display incorrectly.
We suggest using a current version of Chrome,
FireFox, or Safari.
Pharm Res
2019 Apr 17;366:84. doi: 10.1007/s11095-019-2626-3.
Show Gene links
Show Anatomy links
Transport Mechanisms for the Nutritional Supplement β-Hydroxy-β-Methylbutyrate (HMB) in Mammalian Cells.
Ogura J
,
Sato T
,
Higuchi K
,
Bhutia YD
,
Babu E
,
Masuda M
,
Miyauchi S
,
Rueda R
,
Pereira SL
,
Ganapathy V
.
???displayArticle.abstract???
PURPOSE: β-Hydroxy-β-methylbutyrate (HMB), a nutritional supplement, elicits anabolic activity in muscle. Here we investigated the mechanism of HMB uptake in muscle cells.
METHODS: Murine muscle cells (C2C12) and human mammary epithelial cells (MCF7) were used for uptake. As HMB is a monocarboxylate, focus was on monocarboxylate transporters, monitoring interaction of HMB with H+-coupled lactate uptake, and influence of H+ directly on HMB uptake. Involvement of MCT1-4 was studied using selective inhibitors and gene silencing. Involvement of human Na+/monocarboxylate transporter SMCT1 was also assessed using Xenopus oocytes.
RESULTS: H+-coupled lactate uptake was inhibited by HMB in both mammalian cells. HMB uptake was H+-coupled and inhibited by lactate. C2C12 cells expressed MCT1 and MCT4; MCF7 cells expressed MCT1-4; undifferentiated C2C12 cells expressed SMCT1. SMCT1 mediated Na+-coupled HMB transport. Inhibitors of MCT1/4, siRNA-mediated gene silencing, and expression pattern showed that MCT1-4 were responsible only for a small portion of HMB uptake in these cells.
CONCLUSION: HMB uptake in C2C12 and MCF7 cells is primarily H+-coupled and inhibited by lactate, but MCT1-4 are only partly responsible for HMB uptake. SMCT1 also transports HMB, but in a Na+-coupled manner. Other, yet unidentified, transporters mediate the major portion of HMB uptake in C2C12 and MCF7 cells.
???displayArticle.pubmedLink???
30997560
???displayArticle.link???Pharm Res ???displayArticle.grants???[+]
Alway,
β-Hydroxy-β-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy.
2013, Pubmed
Alway,
β-Hydroxy-β-methylbutyrate (HMB) enhances the proliferation of satellite cells in fast muscles of aged rats during recovery from disuse atrophy.
2013,
Pubmed
Clark,
Nutritional treatment for acquired immunodeficiency virus-associated wasting using beta-hydroxy beta-methylbutyrate, glutamine, and arginine: a randomized, double-blind, placebo-controlled study.
2000,
Pubmed
Deutz,
Effect of β-hydroxy-β-methylbutyrate (HMB) on lean body mass during 10 days of bed rest in older adults.
2013,
Pubmed
Doherty,
Blocking lactate export by inhibiting the Myc target MCT1 Disables glycolysis and glutathione synthesis.
2014,
Pubmed
Eley,
Signaling pathways initiated by beta-hydroxy-beta-methylbutyrate to attenuate the depression of protein synthesis in skeletal muscle in response to cachectic stimuli.
2007,
Pubmed
Flakoll,
Effect of beta-hydroxy-beta-methylbutyrate, arginine, and lysine supplementation on strength, functionality, body composition, and protein metabolism in elderly women.
2004,
Pubmed
Futagi,
Identification of a selective inhibitor of human monocarboxylate transporter 4.
2018,
Pubmed
,
Xenbase
Ganapathy,
Sodium-coupled monocarboxylate transporters in normal tissues and in cancer.
2008,
Pubmed
Girón,
β-Hydroxy-β-methylbutyrate (HMB) normalizes dexamethasone-induced autophagy-lysosomal pathway in skeletal muscle.
2015,
Pubmed
Gopal,
Cloning and functional characterization of human SMCT2 (SLC5A12) and expression pattern of the transporter in kidney.
2007,
Pubmed
,
Xenbase
Halestrap,
The SLC16 gene family - structure, role and regulation in health and disease.
2013,
Pubmed
,
Xenbase
Hao,
β-Hydroxy-β-methylbutyrate reduces myonuclear apoptosis during recovery from hind limb suspension-induced muscle fiber atrophy in aged rats.
2011,
Pubmed
Holeček,
Beta-hydroxy-beta-methylbutyrate supplementation and skeletal muscle in healthy and muscle-wasting conditions.
2017,
Pubmed
Kimura,
β-Hydroxy-β-methylbutyrate facilitates PI3K/Akt-dependent mammalian target of rapamycin and FoxO1/3a phosphorylations and alleviates tumor necrosis factor α/interferon γ-induced MuRF-1 expression in C2C12 cells.
2014,
Pubmed
Kovarik,
Effects of β-hydroxy-β-methylbutyrate treatment in different types of skeletal muscle of intact and septic rats.
2010,
Pubmed
May,
Reversal of cancer-related wasting using oral supplementation with a combination of beta-hydroxy-beta-methylbutyrate, arginine, and glutamine.
2002,
Pubmed
Miyauchi,
Functional identification of SLC5A8, a tumor suppressor down-regulated in colon cancer, as a Na(+)-coupled transporter for short-chain fatty acids.
2004,
Pubmed
,
Xenbase
Molfino,
Beta-hydroxy-beta-methylbutyrate supplementation in health and disease: a systematic review of randomized trials.
2013,
Pubmed
Ristic,
Cell-surface G-protein-coupled receptors for tumor-associated metabolites: A direct link to mitochondrial dysfunction in cancer.
2017,
Pubmed
Sabourin,
Formation of beta-hydroxyisovalerate by an alpha-ketoisocaproate oxygenase in human liver.
1983,
Pubmed
Sabourin,
The mechanism of alpha-ketoisocaproate oxygenase. Formation of beta-hydroxyisovalerate from alpha-ketoisocaproate.
1982,
Pubmed
Sivaprakasam,
Short-Chain Fatty Acid Transporters: Role in Colonic Homeostasis.
2017,
Pubmed
Slater,
Beta-hydroxy-beta-methylbutyrate (HMB) supplementation and the promotion of muscle growth and strength.
2000,
Pubmed
Smith,
Attenuation of proteasome-induced proteolysis in skeletal muscle by {beta}-hydroxy-{beta}-methylbutyrate in cancer-induced muscle loss.
2005,
Pubmed
Srinivas,
Cloning and functional identification of slc5a12 as a sodium-coupled low-affinity transporter for monocarboxylates (SMCT2).
2005,
Pubmed
,
Xenbase
Standley,
Effects of β-hydroxy-β-methylbutyrate on skeletal muscle mitochondrial content and dynamics, and lipids after 10 days of bed rest in older adults.
2017,
Pubmed
Stout,
Effect of calcium β-hydroxy-β-methylbutyrate (CaHMB) with and without resistance training in men and women 65+yrs: a randomized, double-blind pilot trial.
2013,
Pubmed
Stout,
β-Hydroxy-β-methylbutyrate (HMB) supplementation and resistance exercise significantly reduce abdominal adiposity in healthy elderly men.
2015,
Pubmed
Szcześniak,
Characterisation of equine satellite cell transcriptomic profile response to β-hydroxy-β-methylbutyrate (HMB).
2016,
Pubmed
Wilkinson,
Effects of leucine and its metabolite β-hydroxy-β-methylbutyrate on human skeletal muscle protein metabolism.
2013,
Pubmed
Wilson,
International Society of Sports Nutrition Position Stand: beta-hydroxy-beta-methylbutyrate (HMB).
2013,
Pubmed
Zanchi,
HMB supplementation: clinical and athletic performance-related effects and mechanisms of action.
2011,
Pubmed
