Journal
JOURNAL OF AGRICULTURAL AND FOOD CHEMISTRY
Volume 68, Issue 2, Pages 530-540Publisher
AMER CHEMICAL SOC
DOI: 10.1021/acs.jafc.9b05104
Keywords
HMB; myofiber type transition; mice; C2C12 cells; miR-199a-3p; TEAD1
Funding
- National Natural Science Foundation of China [31802069]
- National Key Research and Development Program of China [2016YFD0500505]
- Natural Science Foundation of Southwest University of Science and Technology [19zx7115]
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The influence of beta-hydroxy-beta-methylbutyrate (HMB) on proliferation and differentiation of myogenic cells has been well-studied. However, the role of HMB in myofiber specification and potential mechanisms is largely unknown. Thus, the objective of this research was to explore the role of HMB supplementation in myofiber specification. Results showed that HMB treatment significantly increased the fast MyHC protein level (mice: 1.59 +/- 0.08, P < 0.01; C2C12: 2.26 +/- 0.11, P < 0.001), decreased the slow MyHC protein level (mice: 0.76 +/- 0.05, P < 0.05; C2C12: 0.52 +/- 0.02, P < 0.001), and increased the miR-199a-3p level (mice: 4.93 +/- 0.37, P < 0.001; C2C12: 11.25 +/- 0.57, P < 0.001). Besides, we also observed that HMB promoted the activity of glycolysis-related enzymes and reduced the activities of oxidation-related enzymes in mice and C2C12 cells. Overexpression of miR-199a-3p downregulated the slow MyHC protein level (0.71 +/- 0.02, P < 0.01) and upregulated the fast MyHC protein level (2.13 +/- 0.09, P < 0.001), while repression of miR-199a-3p exhibited the opposite effect. Target identification results verified that miR-199a-3p targets the 3'UTR of the TEA domain family member 1 (TEAD1) to cause its post-transcriptional inhibition (0.41 +/- 0.07, P < 0.01). Knockdown of TEAD1 exhibited a similar effect with miR-199a-3p on myofiber specification. Moreover, suppression of miR-199a-3p blocked slow-to-fast myofiber type transition induced by HMB. Together, our finding revealed that miR-199-3p is induced by HMB and contributes to the action of HMB on slow-to-fast myofiber type conversion via targeting TEAD1.
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