RRC ID 27892
著者 Xu L, Kanasaki M, He J, Kitada M, Nagao K, Jinzu H, Noguchi Y, Maegawa H, Kanasaki K, Koya D.
タイトル Ketogenic essential amino acids replacement diet ameliorated hepatosteatosis with altering autophagy-associated molecules.
ジャーナル Biochim Biophys Acta
Abstract Ketogenic amino acid (KAA) replacement diet has been shown to cure hepatic steatosis, a serious liver disease associated with diverse metabolic defects. In this study, we investigated the effects of KAA replacement diet on nutrition sensing signaling pathway and analyzed whether induction of hepatic autophagy was involved. Mice are fed with high fat diet (HFD) or KAA replacement in high-fat diet (30% fat in food; HFD)-fed (HFD(KAAR)) and sacrificed at 8, 12, 16 weeks after initiation of experimental food. Hepatic autophagy was analyzed in protein expression of several autophagy-associated molecules and in light chain-3 green fluorescent protein (LC-3 GFP) transgenic mice. HFD(KAAR) showed increased AMP-activated protein kinase (AMPK) phosphorylation and enhanced liver kinase B1 (LKB1) expression compared to control HFD-fed mice. The KAA-HFD-induced activation of AMPK was associated with an increased protein expression of sirtuin 1 (Sirt1), decreased forkhead box protein O3a (Foxo3a) level, and suppression of mammalian target of rapamycin (mTOR) phosphorylation compared with the HFD-fed mice. The intervention study revealed that a KAA-replacement diet also ameliorated all the established metabolic and autophagy defects in the HFD-fed mice, suggesting that a KAA-replacement diet can be used therapeutically in established diseases. These results indicate that KAA replacement in food could be a novel strategy to combat hepatic steatosis and metabolic abnormalities likely involvement of an induction of autophagy.
巻・号 1832(10)
ページ 1605-12
公開日 2013-10-1
DOI 10.1016/j.bbadis.2013.05.003
PII S0925-4439(13)00157-9
PMID 23669346
MeSH Amino Acids, Essential / administration & dosage* Animals Autophagy* Body Weight Diet, Ketogenic* Dietary Fats / administration & dosage Fatty Liver / diet therapy* Macrophages / physiology Mice Mice, Inbred C57BL Organ Size
IF 3.411
引用数 15
WOS 分野 BIOPHYSICS BIOCHEMISTRY & MOLECULAR BIOLOGY CELL BIOLOGY
リソース情報
実験動物マウス RBRC00806