期刊
BIOCHIMICA ET BIOPHYSICA ACTA-GENERAL SUBJECTS
卷 1862, 期 7, 页码 1547-1555出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.bbagen.2018.03.013
关键词
Ketogenic amino acid; High fat diet; Mitochondrial fusion and fission; Gastrocnemius and the soleus; AKT/4EBP1; Autophagy
资金
- Japan Society for the Promotion of Science [24790329, 24591218, 23790381, 26460403, 25282028, 25670414, 16K15472]
- Kanazawa Medical University
- Kanazawa Medical University [C2011-4, C2012-1, S2015-3, S2016-3, S2017-1, SR2012-06]
- MitsubishiTanabe Pharma
- Ono Pharmaceutical
Muscle biology is important topic in diabetes research. We have reported that a diet with ketogenic amino acids rich replacement (KAAR) ameliorated high-fat diet (HFD)-induced hepatosteatosis via activation of the autophagy system. Here, we found that a KAAR ameliorated the mitochondrial morphological alterations and associated mitochondrial dysfunction induced by an HFD through induction of the AKT/4EBP1 and autophagy signaling pathways in both fast and slow muscles. The mice were fed with a standard HFD (30% fat in food) or an HFD with KAAR (HFDKAAR). In both the gastrocnemius and the soleus, HFDKAAR ameliorated HFD-impaired mitochondrial morphology and mitochondrial function, characterized by decreased mitofusin 2, optic atrophy 1, peroxisome proliferator-activated receptor (PPAR) gamma coactivator-1 alpha and PPAR alpha levels and increased dynamin-related protein 1 levels. The decreased levels of phosphorylated AKT and 4EBP1 in the gastrocnemius and soleus of HFD-fed mice were remediated by HFDKAAR. Furthermore, the HFDKAAR ameliorated the HFD-induced autophagy defects in the gastrocnemius and soleus. These findings suggest that KAAR may be a novel strategy to combat obesity -induced mitochondrial dysfunction, likely through induction of the AKT/4EBP1 and autophagy pathways in skeletal muscle.
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