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. 2016 Jan 4;6(1):43-9.
doi: 10.1002/2211-5463.12007. eCollection 2016 Jan.

mTORC1 is involved in the regulation of branched-chain amino acid catabolism in mouse heart

Hongmin Zhen  1 , Yasuyuki Kitaura  1 , Yoshihiro Kadota  1 , Takuya Ishikawa  1 , Yusuke Kondo  1 , Minjun Xu  1 , Yukako Morishita  1 , Miki Ota  1 , Tomokazu Ito  2 , Yoshiharu Shimomura  1
Affiliations

mTORC1 is involved in the regulation of branched-chain amino acid catabolism in mouse heart

Hongmin Zhen et al. FEBS Open Bio. .

Abstract

The branched-chain α-ketoacid dehydrogenase (BCKDH) complex regulates branched-chain amino acid (BCAA) catabolism by controlling the second step of this catabolic pathway. In the present study, we examined the in vivo effects of treatment with an mTORC1 inhibitor, rapamycin, on cardiac BCKDH complex activity in mice. Oral administration of leucine in control mice significantly activated the cardiac BCKDH complex with an increase in cardiac concentrations of leucine and α-ketoisocaproate. However, rapamycin treatment significantly suppressed the leucine-induced activation of the complex despite similar increases in cardiac leucine and α-ketoisocaproate levels. Rapamycin treatment fully inhibited mTORC1 activity, measured by the phosphorylation state of ribosomal protein S6 kinase 1. These results suggest that mTORC1 is involved in the regulation of cardiac BCAA catabolism.

Keywords: branched‐chain amino acid; branched‐chain α‐ketoacid dehydrogenase complex; leucine; mTORC1.

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Figures

Figure 1
Figure 1
Cardiac BCKDH complex activity in mice. (A) Total and (B) actual activities of the cardiac BCKDH complex. Fasted mice were injected intraperitoneally with rapamycin (4.5 mg·kg−1 body weight) or vehicle. Three hours later, one‐half of each groups of mice were orally administrated saline or leucine. Hearts were collected from mice 30 min after oral administration of saline or leucine. Values are mean ± SE, n = 5–7. Means not sharing the same letters are significantly different, P < 0.05.
Figure 2
Figure 2
Phosphorylation of S6K1 Thr 389 in mouse heart. Total and phosphorylated S6K1 were measured by western blot analysis using anti‐total‐S6K1 and antiphospho‐S6K1 (Thr 389) antibodies, respectively. Representative data for total and phosphorylated S6K1 (P‐S6K1) are shown in the upper panel. The bar graph gives quantification of the relative amounts of phosphorylated S6K1 for each group (mean ± SE, n = 5–7). Means not sharing the same letters are significantly different, P < 0.05.
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