Dietary β-
carotene induces muscle
hypertrophy and prevents
muscle atrophy in red slow-twitch soleus muscles, but not in white fast-twitch extensor digitorum longus (EDL) muscles and gastrocnemius muscles. However, it remains unclear why these beneficial effects of β-
carotene are elicited in soleus muscles. To address this issue, we focused on
carotenoid transporters in skeletal muscles. In mice, Cd36
mRNA levels were higher in red muscle than in white muscle. The
siRNA-mediated knockdown of CD36 decreased β-
carotene uptake in C2C12 myotubes. In soleus muscles, CD36 knockdown inhibited β-
carotene-induced increase in muscle mass.
Intravenous injection of the
hypoxia marker
pimonidazole produced more
pimonidazole-bound
proteins in soleus muscles than in EDL muscles, and the
hypoxia-inducible factor-1 (HIF-1) α
protein level was higher in soleus muscles than in EDL muscles. In C2C12 myotubes,
hypoxia increased the expression of CD36 and HIF-1α at the
protein and
mRNA levels, and HIF-1α knockdown reduced
hypoxia-induced increase in Cd36
mRNA level. In soleus muscles, HIF-1α knockdown reduced Cd36
mRNA level. These results indicate that CD36 is predominantly involved in β-
carotene-induced increase in soleus muscle mass of mice. Furthermore, we demonstrate that CD36 expression depends on HIF-1α in the soleus muscles of mice, even under normal physiological conditions.