Protein plays a significant role in building muscles. However, protein degradation may occur in skeletal muscle and lead to muscle atrophy and death, which highlights the urgent need to develop more effective therapies to inhibit protein degradation and combat muscle atrophy.

β-hydroxy-β-methyl- butyrate (HMB) is a key metabolite of leucine. Previous studies have shown that both HMB and leucine can inhibit muscular protein degradation.

However, questions about which one is more effective, whether insulin contributes to the antiatrophic effects of HMB and leucine, and what the underlying mechanism is still remain unknown.

Recently, using a starvation model, researchers from China Agricultural University and the Institute of Subtropical Agriculture (ISA) of the Chinese Academy of Sciences compared the effects of leucine (within a range that is physiologically relevant) and HMB on protein degradation in order to examine the underlying mechanisms and assess the contribution of insulin in protein analytic response to HMB and leucine.

The researchers found that the inhibitory effect of HMB was more potent than that of Leu and KIC, and was significantly abolished in the presence of LY294002 and rapamycin.

In the presence of insulin, the inhibitory effect of HMB was still more effective than that of Leu and KIC. Interestingly, LY294002 treatment markedly attenuated the effect of HMB, while rapamycin treatment failed to exert the same effect.

Overall, HMB appears to be more potent than leucine in inhibiting protein degradation in the absence or presence of insulin, and this inhibitory effect may depend on PI3K/Akt signaling pathway regardless of insulin. mTOR signaling was only involved in the effect of HMB in the absence of insulin.

The study entitled "β-Hydroxy-β-methyl Butyrate is more potent than leucine in inhibiting starvation-induced protein degradation in C2C12 myotubes" was published in Journal of Agricultural and Food Chemistry.

 Contact: YIN Yulong

E-mail:yinyulong@isa.ac.cn

Institue of Subtropical Agriculture,Chinese Academy of Sciences

Figure: The potential mechanism of HMB effects on inhibiting muscular protein degradation. (Imaged by ISA)