Transport Mechanisms for the Nutritional Supplement β-Hydroxy-β-Methylbutyrate (HMB) in Mammalian Cells

Jiro Ogura, Toshihiro Sato, Kei Higuchi, Yangzom D. Bhutia, Ellappan Babu, Masayuki Masuda, Seiji Miyauchi, Ricardo Rueda, Suzette L. Pereira, Vadivel Ganapathy

Research output: Contribution to journalArticlepeer-review

4 Citations (Scopus)


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.

Original languageEnglish
Article number84
JournalPharmaceutical research
Issue number6
Publication statusPublished - 2019 Jun 1


  • H -coupled transport
  • MCT1 (SLC16A1)
  • MCT4 (SLC16A3)
  • Na -coupled transport
  • SMCT1 (SLC5A8)
  • Skeletal muscle cell

ASJC Scopus subject areas

  • Biotechnology
  • Molecular Medicine
  • Pharmacology
  • Pharmaceutical Science
  • Organic Chemistry
  • Pharmacology (medical)


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