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Dietary lysine restriction induces lipid accumulation in skeletal muscle through an increase in serum threonine levels in rats
Authors:Yuki Goda  Daisuke Yamanaka  Hiroki Nishi  Masato Masuda  Hiroyasu Kamei  Mikako Kumano  Koichi Ito  Masaya Katsumata  Keitaro Yamanouchi  Naoyuki Kataoka  Fumihiko Hakuno  Shin-Ichiro Takahashi
Affiliation:1.Departments of Animal Sciences and Applied Biological Chemistry, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan;2.Department of Veterinary Medical Sciences, Graduate School of Agricultural and Life Sciences, The University of Tokyo, Tokyo, Japan;3.School of Veterinary Science, Azabu University, Sagamihara, Kanagawa, Japan
Abstract:We previously reported that dietary amino acid restriction induces the accumulation of triglycerides (TAG) in the liver of growing rats. However, differences in TAG accumulation in individual cell types or other tissues were not examined. In this study, we show that TAG also accumulates in the muscle and adipose tissues of rats fed a low amino acid (low-AA) diet. In addition, dietary lysine restriction (low-Lys) induces lipid accumulation in muscle and adipose tissues. In adjusting the nitrogen content to that of the control diet, we found that glutamic acid supplementation to the low-AA diet blocked lipid accumulation, but supplementation with the low-Lys diet did not, suggesting that a shortage of nitrogen caused lipids to accumulate in the skeletal muscle in the rats fed a low-AA diet. Serum amino acid measurement revealed that, in rats fed a low-Lys diet, serum lysine levels were decreased, while serum threonine levels were significantly increased compared with the control rats. When the threonine content was restricted in the low-Lys diet, TAG accumulation induced by the low-Lys diet was completely abolished in skeletal muscle. Moreover, in L6 myotubes cultured in medium containing high threonine and low lysine, fatty acid uptake was enhanced compared with that in cells cultured in control medium. These findings suggest that the increased serum threonine in rats fed a low-Lys diet resulted in lipid incorporation into skeletal muscle, leading to the formation of fatty muscle tissue. Collectively, we propose conceptual hypothesis that “amino-acid signal” based on lysine and threonine regulates lipid metabolism.
Keywords:amino acid   fatty acid   lipid transport   lipid metabolism   muscle   lysine   threonine   fiber twitch   lipid accumulation   amino acid restriction
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