Journal of Food, Nutrition and Population Health Open Access

The retinoic acid receptor responsive gene transglutaminase 2 induces myotube hypertrophy as a secretory protein

International Conference on Nutritional Biochemistry

September 10-11, 2018 Prague , Czech Republic

Yamaji R, Kitakaze T, Yoshikawa M and Harada N

Osaka Prefecture University, Japan Kobe University, Japan

Scientific Tracks Abstracts: J Food Nutr Popul Health

Abstract:

Skeletal muscle plays critical roles not only in physical activity such as posture and locomotion, but also in metabolism of glucose and lipids. The loss of skeletal muscle mass results in physical inactivity and higher prevalence of metabolic diseases such as obese and type 2 diabetes. The provitamin A β-carotene is the major dietary source of vitamin A. β-carotene is converted into all-trans retinal and is metabolized to all-trans retinoic acid (ATRA). Our previous study showed that dietary β-carotene increases mass and induces functional hypertrophy in the soleus muscle in mice. However, its molecular mechanism remains unclear. In the present study, we investigated whether or how retinoic acid receptor is involved in β-carotene-increased muscle mass. Small interference RNA (siRNA) mediated knockdown of RARγ inhibited β-carotene-increased soleus muscle mass in mice. Conditioned medium from ATRA-stimulated myotubes promoted protein synthesis and induced hypertrophy in murine C2C12 myotubes. We used RNA-sequencing and bioinformatics analyses to study gene expression of ATRA-dependent secreted proteins. Transglutaminase 2 (TGM2) was predicted to be one of ATRAincreased secretory proteins in myotubes. In the soleus muscle of β-caroteneadministered mice and in ATRA-stimulated myotubes, the expression of TGM2 was increased. Knockdown of RARγ has down-regulated ATRA- or β-carotenedependent TGM2 expression. TGM2 expression was increased in conditioned medium from ATRA-stimulated myotubes. Extracellular recombinant TGM2 promoted protein synthesis and hypertrophy and induced the phosphorylation of Akt, mTOR and p70S6K in myotubes. These results indicated that ATRA upregulated TGM2 expression through RARγ and that extracellular TGM2 induced myotube hypertrophy, perhaps by activating Akt-mTOR signaling-mediated protein synthesis.

Biography :

Yamaji R has completed his PhD in Osaka Prefecture University, Japan. He is the Professor of Osaka Prefecture University. He is interested in what kinds of food components including nutrients have beneficial effects on skeletal muscle health and how they exert their function. He is serving as an Editorial Board Member of J Nutr Sci Vitaminol.

E-mail: yamaji@biochem.osakafu-u.ac.jp