Kido Y

References (4)

Title : Hepatic FASN deficiency differentially affects nonalcoholic fatty liver disease and diabetes in mouse obesity models - Matsukawa_2023_JCI.Insight_8__e161282
Author(s) : Matsukawa T , Yagi T , Uchida T , Sakai M , Mitsushima M , Naganuma T , Yano H , Inaba Y , Inoue H , Yanagida K , Uematsu M , Nakao K , Nakao H , Aiba A , Nagashima Y , Kubota T , Kubota N , Izumida Y , Yahagi N , Unoki-Kubota H , Kaburagi Y , Asahara SI , Kido Y , Shindou H , Itoh M , Ogawa Y , Minami S , Terauchi Y , Tobe K , Ueki K , Kasuga M , Matsumoto M
Ref : JCI Insight , 8 : , 2023
Abstract : Nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes are interacting comorbidities of obesity, and increased hepatic de novo lipogenesis (DNL), driven by hyperinsulinemia and carbohydrate overload, contributes to their pathogenesis. Fatty acid synthase (FASN), a key enzyme of hepatic DNL, is upregulated in association with insulin resistance. However, the therapeutic potential of targeting FASN in hepatocytes for obesity-associated metabolic diseases is unknown. Here, we show that hepatic FASN deficiency differentially affects NAFLD and diabetes depending on the etiology of obesity. Hepatocyte-specific ablation of FASN ameliorated NAFLD and diabetes in melanocortin 4 receptor-deficient mice but not in mice with diet-induced obesity. In leptin-deficient mice, FASN ablation alleviated hepatic steatosis and improved glucose tolerance but exacerbated fed hyperglycemia and liver dysfunction. The beneficial effects of hepatic FASN deficiency on NAFLD and glucose metabolism were associated with suppression of DNL and attenuation of gluconeogenesis and fatty acid oxidation, respectively. The exacerbation of fed hyperglycemia by FASN ablation in leptin-deficient mice appeared attributable to impairment of hepatic glucose uptake triggered by glycogen accumulation and citrate-mediated inhibition of glycolysis. Further investigation of the therapeutic potential of hepatic FASN inhibition for NAFLD and diabetes in humans should thus consider the etiology of obesity.
ESTHER : Matsukawa_2023_JCI.Insight_8__e161282
PubMedSearch : Matsukawa_2023_JCI.Insight_8__e161282
PubMedID: 37681411
Gene_locus related to this paper: human-FASN , mouse-FASN

Title : Complete biosynthetic pathways of ascofuranone and ascochlorin in Acremonium egyptiacum - Araki_2019_Proc.Natl.Acad.Sci.U.S.A_116_8269
Author(s) : Araki Y , Awakawa T , Matsuzaki M , Cho R , Matsuda Y , Hoshino S , Shinohara Y , Yamamoto M , Kido Y , Inaoka DK , Nagamune K , Ito K , Abe I , Kita K
Ref : Proc Natl Acad Sci U S A , 116 :8269 , 2019
Abstract : Ascofuranone (AF) and ascochlorin (AC) are meroterpenoids produced by various filamentous fungi, including Acremonium egyptiacum (synonym: Acremonium sclerotigenum), and exhibit diverse physiological activities. In particular, AF is a promising drug candidate against African trypanosomiasis and a potential anticancer lead compound. These compounds are supposedly biosynthesized through farnesylation of orsellinic acid, but the details have not been established. In this study, we present all of the reactions and responsible genes for AF and AC biosyntheses in A. egyptiacum, identified by heterologous expression, in vitro reconstruction, and gene deletion experiments with the aid of a genome-wide differential expression analysis. Both pathways share the common precursor, ilicicolin A epoxide, which is processed by the membrane-bound terpene cyclase (TPC) AscF in AC biosynthesis. AF biosynthesis branches from the precursor by hydroxylation at C-16 by the P450 monooxygenase AscH, followed by cyclization by a membrane-bound TPC AscI. All genes required for AC biosynthesis (ascABCDEFG) and a transcriptional factor (ascR) form a functional gene cluster, whereas those involved in the late steps of AF biosynthesis (ascHIJ) are present in another distantly located cluster. AF is therefore a rare example of fungal secondary metabolites requiring multilocus biosynthetic clusters, which are likely to be controlled by the single regulator, AscR. Finally, we achieved the selective production of AF in A. egyptiacum by genetically blocking the AC biosynthetic pathway; further manipulation of the strain will lead to the cost-effective mass production required for the clinical use of AF.
ESTHER : Araki_2019_Proc.Natl.Acad.Sci.U.S.A_116_8269
PubMedSearch : Araki_2019_Proc.Natl.Acad.Sci.U.S.A_116_8269
PubMedID: 30952781
Gene_locus related to this paper: acreg-ascc

Title : Polysaccharide hydrolase of the hadal zone amphipods Hirondellea gigas - Kobayashi_2018_Biosci.Biotechnol.Biochem_82_1123
Author(s) : Kobayashi H , Nagahama T , Arai W , Sasagawa Y , Umeda M , Hayashi T , Nikaido I , Watanabe H , Oguri K , Kitazato H , Fujioka K , Kido Y , Takami H
Ref : Biosci Biotechnol Biochem , 82 :1123 , 2018
Abstract : Hirondellea species are common inhabitants in the hadal region deeper than 7,000 m. We found that Hirondellea gigas thrived in the Challenger Deep possessed polysaccharide hydrolases as digestive enzymes. To obtain various enzymes of other H. gigas, we captured amphipods from the Japan Trench, and Izu-Ogasawara (Bonin) Trench. A phylogenetic analysis based on the cytochrome oxidase I gene showed close relationships among amphipods, despite the geographic distance between the localities. However, several differences in enzymatic properties were observed in these H. gigas specimens. We also carried out RNA sequencing of H. gigas from the Izu-Ogasawara Trench. The cellulase gene of H. gigas was highly homologous to cellobiohydrolase of Glucosyl Hydrolase family 7 (GH7). On the other hand, enzymatic properties of H. gigas's cellulase were different from those of typical GH7 cellobiohydrolase. Thus, these results indicate that hadal-zone amphipod can be good candidates as the new enzyme resource.
ESTHER : Kobayashi_2018_Biosci.Biotechnol.Biochem_82_1123
PubMedSearch : Kobayashi_2018_Biosci.Biotechnol.Biochem_82_1123
PubMedID: 29623763
Gene_locus related to this paper: 9crus-a0a2p2i2d2 , 9crus-a0a2p2ic40

Title : Trypanosome alternative oxidase, a potential therapeutic target for sleeping sickness, is conserved among Trypanosoma brucei subspecies - Nakamura_2010_Parasitol.Int_59_560
Author(s) : Nakamura K , Fujioka S , Fukumoto S , Inoue N , Sakamoto K , Hirata H , Kido Y , Yabu Y , Suzuki T , Watanabe Y , Saimoto H , Akiyama H , Kita K
Ref : Parasitol Int , 59 :560 , 2010
Abstract : Trypanosoma brucei rhodesiense and T. b. gambiense are known causes of human African trypanosomiasis (HAT), or "sleeping sickness," which is deadly if untreated. We previously reported that a specific inhibitor of trypanosome alternative oxidase (TAO), ascofuranone, quickly kills African trypanosomes in vitro and cures mice infected with another subspecies, non-human infective T. b. brucei, in in vivo trials. As an essential factor for trypanosome survival, TAO is a promising drug target due to the absence of alternative oxidases in the mammalian host. This study found TAO expression in HAT-causing trypanosomes; its amino acid sequence was identical to that in non-human infective T. b. brucei. The biochemical understanding of the TAO including its 3 dimensional structure and inhibitory compounds against TAO could therefore be applied to all three T. brucei subspecies in search of a cure for HAT. Our in vitro study using T. b. rhodesiense confirmed the effectiveness of ascofuranone (IC(50) value: 1 nM) to eliminate trypanosomes in human infective strain cultures.
ESTHER : Nakamura_2010_Parasitol.Int_59_560
PubMedSearch : Nakamura_2010_Parasitol.Int_59_560
PubMedID: 20688188
Gene_locus related to this paper: acreg-ascc