研究者詳細 - 池田　真一

論文 - 池田　真一

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Oral crocetin administration suppressed refractive shift and axial elongation in a murine model of lens-induced myopia

Mori K., Kurihara T., Miyauchi M., Ishida A., Jiang X., Ikeda S., Torii H., Tsubota K.

Scientific Reports （Scientific Reports） 9 （ 1 ） 2019年12月

© 2019, The Author(s). Increased global incidence of myopia necessitates establishment of therapeutic approaches against its progression. To explore agents which may control myopia, we screened 207 types of natural compounds and chemical reagents based on an activity of a myopia suppressive factor, early growth response protein 1 (Egr-1) in vitro. Among the candidates, crocetin showed the highest and dose-dependent activation of Egr-1. For in vivo analysis, experimental myopia was induced in 3-week-old C57BL/6 J mice with −30 diopter (D) lenses for 3 weeks. Animals were fed with normal or mixed chow containing 0.003% (n = 19) and 0.03% (n = 7) of crocetin during myopia induction. Refraction and axial length were measured at 3-week-old and the 6-week-old with an infrared photorefractor and a SD-OCT system. Compared to controls (n = 14), crocetin administration showed a significant smaller change of refractive errors (−13.62 ± 8.14 vs +0.82 ± 5.81 D for 0.003%, p < 0.01, −2.00 ± 4.52 D for 0.03%, p < 0.01) and axial elongation (0.27 ± 0.03 vs 0.22 ± 0.04 mm for 0.003%, p < 0.01, 0.23 ± 0.05 mm for 0.03%, p < 0.05). These results suggest that a dietary factor crocetin may have a preventive effect against myopia progression.

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Effects of hyperoxia on the refraction in murine neonatal and adult models

Mori K., Kurihara T., Jiang X., Ikeda S., Ishida A., Torii H., Tsubota K.

International Journal of Molecular Sciences （International Journal of Molecular Sciences） 20 （ 23 ） 2019年12月

ISSN 16616596

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. Whether hyperoxia affects the refraction in neonatal and adult mice is unknown. The mice exposed to 85% oxygen at postnatal 8 days (P8d) for 3 days and the mice exposed to normal air were assigned to the neonatal hyperoxia and normoxia groups, respectively. The refraction, the corneal curvature radius (CR) and the axial length (AL) were measured at P30d and P47d. Postnatal 6 weeks (P6w) adult mice were divided into the adult hyperoxia and normoxia groups. These parameters were measured before oxygen exposure, after 1 and 6 weeks, and every 7 weeks. The lens elasticity was measured at P7w and P26w by enucleation. The neonatal hyperoxia group showed a significantly larger myopic change than the neonatal normoxia group (P47d −6.56 ± 5.89 D, +4.11 ± 2.02 D, p < 0.001), whereas the changes in AL were not significantly different (P47d, 3.31 ± 0.04 mm, 3.31 ± 0.05 mm, p = 0.852). The adult hyperoxia group also showed a significantly larger myopic change (P12w, −7.20 ± 4.09 D, +7.52 ± 2.54 D, p < 0.001). The AL did not show significant difference (P12w, 3.44 ± 0.03 mm, 3.43 ± 0.01 mm, p = 0.545); however, the CR in the adult hyperoxia group was significantly smaller than the adult normoxia group (P12w, 1.44 ± 0.03 mm, 1.50 ± 0.03 mm, p = 0.003). In conclusion, hyperoxia was demonstrated to induce myopic shift both in neonatal and adult mice, which was attributed to the change in the CR rather than the AL. Elucidation of the mechanisms of hyperoxia and the application of this result to humans should be carried out in future studies.

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Ocular-component-specific miRNA expression in a murine model of lens-induced myopia

Tanaka Y., Kurihara T., Hagiwara Y., Ikeda S., Mori K., Jiang X., Torii H., Tsubota K.

International Journal of Molecular Sciences （International Journal of Molecular Sciences） 20 （ 15 ） 2019年08月

ISSN 16616596

© 2019 by the authors. Licensee MDPI, Basel, Switzerland. To identify tissues and molecules involved in refractive myopic shift and axial length elongation in a murine lens-induced myopia model, we performed a comprehensive analysis of microRNA (miRNA) expression. Three weeks after negative 30 diopter lens fixation on three-week-old C57BL/6J mice, total RNA was extracted from individual ocular components including cornea, iris, lens, retina, retinal pigment epithelium (RPE)/choroid, and sclera tissue. The miRNA expression analysis was pooled from three samples and carried out using Agilent Mouse miRNA Microarray (8 × 60 K) miRBase21.0. The expression ratio was calculated, and differentially expressed miRNAs were extracted, using GeneSpring GX 14.5. Myopic induction showed a significant myopic refractive change, axial elongation, and choroidal thinning. Through the comprehensive miRNA analysis, several upregulated miRNAs (56 in cornea tissue, 13 in iris tissue, 6 in lens tissue, 0 in retina tissue, 29 in RPE/choroid tissue, and 30 in sclera tissue) and downregulated miRNAs (7 in cornea tissue, 28 in iris tissue, 17 in lens tissue, 9 in retina tissue, 7 in RPE/choroid tissue, and 40 in sclera tissue) were observed. Overlapping expression changes in miRNAs were also found in different ocular components. Some of this miRNA dysregulation may be functionally involved in refractive myopia shift and axial length elongation.

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The effect of dietary supplementation of crocetin for myopia control in children: A randomized clinical trial

Mori K., Torii H., Fujimoto S., Jiang X., Ikeda S.I., Yotsukura E., Koh S., Kurihara T., Nishida K., Tsubota K.

Journal of Clinical Medicine （Journal of Clinical Medicine） 8 （ 8 ） 2019年08月

The prevalence of myopia has been increasing in recent years. The natural carotenoid crocetin has been reported to suppress experimental myopia in mice. We evaluated the effects of crocetin on myopia suppression in children. A multicenter randomized double-blind placebo-controlled clinical trial was performed with 69 participants aged 6 to 12 years, whose cycloplegic spherical equivalent refractions (SER) were between −1.5 and −4.5 diopter (D). The participants were randomized to receive either a placebo or crocetin and followed up for 24 weeks. Axial length (AL) elongation and changes in SER were evaluated for 24 weeks. Both written informed assent from the participants and written informed consent from legal guardians were obtained in this study because the selection criteria of this trial included children aged between 6 and 12 years old. This trial was approved by the institutional review boards. A mixed-effects model was used for analysis, using both eyes. Two participants dropped out and 67 children completed this trial. The change in SER in the placebo group, −0.41 ± 0.05 D (mean ± standard deviation), was significantly more myopic compared to that in the crocetin group, −0.33 ± 0.05 D (p = 0.049). The AL elongation in the placebo group, 0.21 ± 0.02 mm, was significantly bigger than that in the crocetin group, 0.18 ± 0.02 mm (p = 0.046). In conclusion, dietary crocetin may have a suppressive effect on myopia progression in children, but large-scale studies are required in order to confirm this effect.

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バイオレットライトを使用した前向き研究における成人強度近視2症例の眼軸長伸長量

鳥居秀成, 戸田郁子, 大野綾香, 近藤眞一郎, 四倉絵里沙, 森紀和子, 小橋英長, 姜効炎, 池田真一, 栗原俊英, 坪田一男

日本眼科学会雑誌（(公財)日本眼科学会） 123 （臨増） 182 - 182 2019年03月

ISSN 0029-0203

マウス近視モデルにおけるバイオレットライト(VL)近視抑制効果の波長特異性

姜效炎, 栗原俊英, 池田真一, 森紀和子, 鳥居秀成, 坪田一男

日本眼科学会雑誌（(公財)日本眼科学会） 123 （臨増） 304 - 304 2019年03月

ISSN 0029-0203

マウス近視モデルにおけるクロセチンの近視抑制効果

森紀和子, 栗原俊英, 石田文子, 姜效炎, 池田真一, 鳥居秀成, 坪田一男

日本眼科学会雑誌（(公財)日本眼科学会） 123 （臨増） 305 - 305 2019年03月

ISSN 0029-0203

ブラジル赤道部付近における学童の1年間の屈折値変化量と眼軸長変化量

四倉絵里沙, 鳥居秀成, 内野美樹, 白石哲郎, 岡直幸, 森紀和子, 姜効炎, 池田真一, 栗原俊英, 根岸一乃, 坪田一男

日本眼科学会雑誌（(公財)日本眼科学会） 123 （臨増） 183 - 183 2019年03月

ISSN 0029-0203

Inducement and evaluation of a murine model of experimental myopia

Jiang X., Kurihara T., Ikeda S., Kunimi H., Mori K., Torii H., Tsubota K.

Journal of Visualized Experiments （Journal of Visualized Experiments） 2019 （ 143 ） 2019年01月

ISSN 1940087X

© 2019 Journal of Visualized Experiments. Murine model of myopia can be a powerful tool for myopia research because of the comparatively easy genetic manipulation. One way to induce myopia in animals is to put clear minus lenses in front of eyes for weeks (lens-induced myopia, LIM). However, extant protocols for inducement and evaluation vary from laboratory to laboratory. Here, we described a highly practical and reproducible method to induce LIM in mice using newly designed eyeglasses. The method fixes the lens stably in front of the mouse eye while allows the lens to be taken off for cleaning or topical drug administration. The phenotype is robust and efficient, and the variance is small. The method described here can be applied to mice right after weaning which extends the possible duration for experiments. We also gave technical advises for achieving reproducible results in refraction and axial length measurements. We hope the step-by-step protocol described here and the detailed article can help researchers perform myopia experiments with myopia more smoothly and make the data comparable across laboratories.

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Current Prevalence of Myopia and Association of Myopia with Environmental Factors among Schoolchildren in Japan

Yotsukura E., Torii H., Inokuchi M., Tokumura M., Uchino M., Nakamura K., Hyodo M., Mori K., Jiang X., Ikeda S., Kondo S., Negishi K., Kurihara T., Tsubota K.

JAMA Ophthalmology （JAMA Ophthalmology） 137 （ 11 ） 1233 - 1239 2019年

ISSN 21686165

© 2019 American Medical Association. All rights reserved. Importance: Given the estimates of increasing prevalence of myopia, especially in Asia, it is important to determine the current prevalence of myopia among populations of schoolchildren in Japan. Objective: To investigate the current prevalence rate of myopia and the association between environmental factors and myopia in Japanese schoolchildren. Design, Setting, and Participants: This cross-sectional study assessed 1478 participants, including 726 elementary school students and 752 junior high school students, at 2 schools in Tokyo, Japan, who underwent eye examinations from April 1 to May 31, 2017, that included measurement of the refractive errors by autorefractometry with noncycloplegic refraction and ocular biometric factors. After excluding those who had been treated with atropine or orthokeratology (n = 11), had a history of eye disease (n = 2), had no parental consent (n = 41), and were absent (n = 8), 1416 schoolchildren were analyzed. Main Outcomes and Measures: The primary outcome was the prevalence of myopia and high myopia. Secondary outcomes were environmental factors that were associated with myopia. Results: A total of 1416 schoolchildren (mean [SD] age, 10.8 [2.7] years; 792 [55.9%] male) were studied. The prevalence rates of myopia (spherical equivalent ≤-0.5 diopters [D]) were 76.5% (95% CI, 73.4%-79.7%) among the elementary school students and 94.9% (95% CI, 93.3%-96.5%) among the junior high school students. The prevalence rates of high myopia (spherical equivalent ≤-6.0 D) were 4.0% (95% CI, 2.5%-5.4%) among the elementary school students and 11.3% (95% CI, 8.8%-13.7%) among the junior high school students. The prevalence rates of high myopia classified based on axial length of 26.0 mm or longer were 1.2% (95% CI, 0.4%-2.0%) among elementary school students and 15.2% (95% CI, 12.5%-17.8%) among junior high school students. Multiple regression analysis showed that higher-order aberrations and dry eye disease were associated with refractive error in elementary school students (spherical aberration: β = 6.152; 95% CI, 3.161-9.143; P <.001; dry eye disease: β = -0.626; 95% CI, -1.189 to -0.063; P =.03) and with axial length in junior high school students (spherical-like aberration: β = 26.546; 95% CI, 18.708-34.385; P <.001; dry eye disease: β = 0.354; 95% CI, 0.131-0.578; P <.002). Conclusions and Relevance: Although the use of noncycloplegic autorefraction with a cutoff of -0.50 D could lead to overestimation of results, these findings suggest that the current prevalence rates of myopia among elementary and junior high school students in Asia are high, especially if the results from these 2 schools are generalizable to all schoolchildren in Japan and Asia..

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A highly efficient murine model of experimental myopia

Jiang X., Kurihara T., Kunimi H., Miyauchi M., Ikeda S., Mori K., Tsubota K., Torii H., Tsubota K.

Scientific Reports （Scientific Reports） 8 （ 1 ） 2018年12月

ISSN 2045-2322

© 2018 The Author(s). Despite the global pandemic of myopia, the precise molecular mechanism of the onset of myopia remains largely unknown. This is partially because of the lack of efficient murine myopic models that allow genetic manipulation at low cost. Here we report a highly practical and reproducible lens-induced myopia model by specially designed frames and lenses for mice. A lens power dependent myopic induction in mice was shown until minus 30 diopter lenses. The phenotype was significantly stronger than form-deprivation myopia. We presented the protocol for precise evaluations of the state of myopia, including refraction, corneal curvature and axial length using up-to-date devices. We also found that myopic mouse eyes showed decreased visual acuity on optokinetic response examination. Finally, we confirmed the anti-myopic effect of 1% atropine using this model, which showed its potential in drug screening. The strong phenotype, stable evaluation and the potential for gene manipulation utilizing the presented method in mice will accelerate the translational research of myopia.

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Exercise-induced increase in IL-6 level enhances GLUT4 expression and insulin sensitivity in mouse skeletal muscle

8. Shin-ichi Ikeda, Yoshifumi Tamura, Saori Kakehi, Kageumi Takeno, Yoshio Fujitani, Ryuzo Kawamori and Hirotaka Watada

Biochemical and Biophysical Research Communication （Biochemical and Biophysical Research Communication） 473 （ 4 ） 947 - 952 2016年05月

ISSN 0006-291X

A single bout of exercise is known to increase the insulin sensitivity of skeletal muscle; however, the underlying mechanism of this phenomenon is not fully understood. Because a single bout of exercise induces a transient increase in blood interleukin-6 (IL-6) level, we hypothesized that the enhancement of insulin sensitivity after a single bout of exercise in skeletal muscle is mediated at least in part through IL-6-dependent mechanisms. To test this hypothesis, C57BL6J mice were intravenously injected with normal IgG or an IL-6 neutralizing antibody before exercise. Twenty-four hours after a single bout of exercise, the plantaris muscle was harvested to measure insulin sensitivity and glucose transporter (GLUT)-4 expression levels by ex-vivo insulin-stimulated 2-deoxyglucose (2-DG) uptake and Western blotting, respectively. Compared with sedentary mice, mice that performed exercise showed enhanced IL-6 concentration, insulin-stimulated 2-DG uptake, and GLUT-4 expression in the plantaris muscle. The enhanced insulin sensitivity and GLUT4 expression were canceled by injection of the IL-6 neutralizing antibody before exercise. In addition, IL-6 injection increased GLUT4 expression, both in the plantaris muscle and the soleus muscle in C57BL6J mice. Furthermore, a short period of incubation with IL-6 increased GLUT4 expression in differentiated C2C12 myotubes. In summary, these results suggested that IL-6 increased GLUT4 expression in muscle and that this phenomenon may play a role in the post-exercise enhancement of insulin sensitivity in skeletal muscle. (C) 2016 Elsevier Inc. All rights reserved.

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Increased intramyocellular lipid/impaired insulin sensitivity is associated with altered lipid metabolic genes in muscle of high responders to a high fat diet

Saori Kakehi, Yoshifumi Tamura, Kageumi Takeno, Yuko Sakurai, Minako Kawaguchi, Takashi Watanabe, Takashi Funayama, Fumihiko Sato, Shin-ichi Ikeda, Akio Kanazawa, Yoshio Fujitani, Ryuzo Kawamori, Hirotaka Watada

American Journal of Physiology-Endocrinology and Metabolism （American Physiological Society） 310 （ 1 ） 32 - 40 2016年01月

査読有り, ISSN 0193-1849

The accumulation of intramyocellular lipid (IMCL) is recognized as an important determinant of insulin resistance, and is increased by a high-fat diet (HFD). However, the effects of HFD on IMCL and insulin sensitivity are highly variable. The aim of this study was to identify the genes in muscle that are related to this inter-individual variation. Fifty healthy men were recruited for this study. Before and after HFD for 3 days, IMCL levels in the tibialis anterior were measured by H-1 magnetic resonance spectroscopy, and peripheral insulin sensitivity was evaluated by glucose infusion rate (GIR) during the euglycemic-hyperinsulinemic clamp. Subjects who showed a large increase in IMCL and a large decrease in GIR by HFD were classified as high responders (HRs), and subjects who showed a small increase in IMCL and a small decrease in GIR were classified as low responders (LRs). In five subjects from each group, the gene expression profile of the vastus lateralis muscle was analyzed by DNA microarray analysis. Before HFD, gene expression profiles related to lipid metabolism were comparable between the two groups. Gene Set Enrichment Analysis demonstrated that five gene sets related to lipid metabolism were upregulated by HFD in the HR group but not in the LR group. Changes in gene expression patterns were confirmed by qRT-PCR using more samples (LR, n = 9; HR, n = 11). These results suggest that IMCL accumulation/impaired insulin sensitivity after HFD is closely associated with changes in the expression of genes related to lipid metabolism in muscle.

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Telogen elongation in the hair cycle of ob/ob mice

Natsumi Tasaki, Takeo Minematsu, Shin-ichi Ikeda, Yuko Mugita, Gojiro Nakagami, Hiromi Sanada

Bioscience, Biotechnology, and Biochemistry （Bioscience, Biotechnology, and Biochemistry） 4 （ 1 ） 1 - 6 2015年08月

査読有り

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Pseudomonas aeruginosa quorum-sensing signaling molecule N-3-oxododecanoyl homoserine lactone induces matrix metalloproteinase 9 expression via the AP1 pathway in rat fibroblasts

Gojiro Nakagami, Takeo Minematsu, Tomohiro Morohoshi, Takumi Yamane, Toshiki Kanazawa, Lijuan Huang, Mayumi Asada, Takashi Nagase, Shin-ichi Ikeda, Tsukasa Ikeda, Hiromi Sanada

Bioscience, Biotechnology, and Biochemistry （Bioscience, Biotechnology, and Biochemistry） 22 （ 10 ） 1 - 5 2015年06月

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Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver

Takahiro Watanabe, Yoshifumi Tamura, Saori Kakehi, Takashi Funayama, Amalia Gastaldelli, Kageumi Takeno, Minako Kawaguchi, Risako Yamamoto, Fumihiko Sato, Shin-ichi Ikeda, Hikari Taka, Tsutomu Fujimura, Yoshio Fujitani, Ryuzo Kawamori and Hirotaka Watada

Journal of Diabetes Investigation （Journal of Diabetes Investigation） 6 （ 2 ） 164 - 172 2015年03月

査読有り

Effects of sitagliptin on ectopic fat contents and glucose metabolism in type 2 diabetic patients with fatty liver: A pilot study

JOURNAL OF DIABETES INVESTIGATION （WILEY-BLACKWELL） 6 （ 2 ） 164 - 172 2015年03月

査読有り, ISSN 2040-1116

Aims/IntroductionRecent data have shown that ectopic fat accumulation in the liver worsens hepatic glucose metabolism, suggesting that fatty liver in patients with type2 diabetes is a therapeutic target. Glucagon-like peptide (GLP)-1 improves fatty liver, but the effect of dipeptidyl peptidase-4 inhibitor on fatty liver is still unclear. The present pilot study determined the effects of 12-week treatment with sitagliptin, a dipeptidyl peptidase-4 inhibitor, on liver fat content in type 2 diabetes with fatty liver. We also evaluated intramyocellular lipid (IMCL) and glucose kinetics during oral glucose tolerance test (OGTT) before and after the treatment.
Materials and MethodsThe study participants were seven type 2 diabetes patients with fatty liver who were studied at baseline and 12weeks after sitagliptin treatment. Intrahepatic lipid (IHL) and IMCL were assessed by H-1 magnetic resonance spectroscopy. Glucose kinetics was assessed during double-tracer OGTT (U-[C-13]-glucose orally and 6,6-[H-2(2)]-glucose intravenously).
ResultsSitagliptin significantly reduced glycated hemoglobin (from 7.10.2 to 6.5 +/- 0.3%, P<0.005), but had no effects on IHL and IMCL. The glucose level diminished, whereas GLP-1 concentration increased during OGTT at the end of treatment. These changes were not accompanied by significant changes in insulin or glucagon levels. However, long-term sitagliptin treatment partially decreased the rate of appearance of oral glucose during OGTT, but did not affect endogenous glucose production or the rate of disappearance.
ConclusionsIt was found that 12-week sitagliptin treatment improved glycated hemoglobin and glucose excursion during OGTT in type 2 diabetes with fatty liver, independent of changes in lipid accumulation in the liver. This trial was registered with the Japan Clinical Trials Registry (UMIN-CTR000005666).

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A treadmill exercise reactivates the signaling of the mammalian target of rapamycin (mTor) in the skeletal muscles of starved mice

Dong-mei Zheng, Zehua Bian, Norihiko Furuya, Mitsue Takeda-Ezaki, Juan Alejandro Oliva Trejo, Katsuyuki Takahashi, Yuka Hiraoka, Reiko Mineki, Hikari Taka, Shin-ichi Ikeda, Masaaki Komatsu, Tsutomu Fujimura, Takashi Ueno and Junji Ezaki

Biochemical and Biophysical Research Communications （Biochemical and Biophysical Research Communications） 456 （ 1 ） 519 - 526 2015年01月

査読有り, ISSN 0006-291X

It has been well established that a starvation-induced decrease in insulin/IGF-I and serum amino acids effectively suppresses the mammalian target of rapamycin (mTor) signaling to induce autophagy, which is a major degradative cellular pathway in skeletal muscles. In this study, we investigated the systematic effects of exercise on the mTor signaling of skeletal muscles. Wild type C57BL/6J mice were starved for 24 h under synchronous autophagy induction conditions. Under these conditions, endogenous LC3-II increased, while both S6-kinse and S6 ribosomal protein were dephosphorylated in the skeletal muscles, which indicated mTor inactivation. Using GFP-LC3 transgenic mice, it was also confirmed that fluorescent GFP-LC3 dots in the skeletal muscles increased, including soleus, plantaris, and gastrocnemius, which clearly showed autophagosomal induction. These starved mice were then subjected to a single bout of running on a treadmill (12 m/min, 2 h, with a lean of 10 degrees). Surprisingly, biochemical analyses revealed that the exercise elicited a decrease in the LC3-II/LC3-I ratio as well as an inversion from the dephosphorylated state to the rephosphorylated state of S6-kinase and ribosomal S6 in these skeletal muscles. Consistently, the GFP-LC3 dots of the skeletal muscles were diminished immediately after the exercise. These results indicated that exercise suppressed starvation-induced autophagy through a reactivation of mTor signaling in the skeletal muscles of these starved mice. (C) 2014 Elsevier Inc. All rights reserved.

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Association between expression of FABPpm in skeletal muscle and insulin sensitivity in intramyocellular-lipid-accumulated non-obese men

Minako Kawaguchi, Yoshifumi Tamura, Saori Kakehi, Kageumi Takeno, Yuko Sakurai, Takahiro Watanabe, Takashi Funayama, Fumihiko Sato, Shin-ichi Ikeda, Yuji Ogura, Norio Saga, Hisashi Naito, Yoshio Fujitani, Akio Kanazawa, Ryuzo Kawamori, and Hirotaka Watada

The Journal of Clinical Endocrinology & Metabolism （The Journal of Clinical Endocrinology & Metabolism） 99 （ 9 ） 3343 - 3352 2014年09月

査読有り, ISSN 0021-972X

Context: Intramyocellular lipid (IMCL) accumulation is observed in both insulin-resistant subjects and insulin-sensitive endurance athletes (athlete's paradox). We hypothesized that the expression pattern of fatty acid transporters may influence oxidative capacity and determine the association between IMCL and insulin resistance.
Objective: The objective of the study was to investigate the muscle expression of fatty acid transporters and their function related to insulin sensitivity in IMCL-accumulated subjects.
Design and Setting: The study subjects were 36 nonobese healthy men. Their IMCL levels were measured by H-1-magnetic resonance spectroscopy, and their insulin sensitivity was evaluated by steady-state glucose infusion rate (GIR) during a euglycemic-hyperinsulinemic clamp. Gene expression levels in the vastus lateralis were evaluated by quantitative RT-PCR. We compared the clinical phenotypes and the expression levels of genes involved in lipid metabolism in skeletal muscle between IMCL-accumulated high-GIR (H-GIR) subjects (n = 8) and low-GIR subjects (n = 9). The functions of candidate fatty acid transporters were determined by in vitro analyses.
Results: Compared with the low-GIR group, body fat was lower and maximum oxygen uptake was higher in the H-GIR group. Several lipid oxidation genes in muscle were up-regulated in the H-GIR group, and this was associated with increased expression of higher plasma membrane-associated fatty acid-binding protein (FABPpm) and decreased expression of fatty acid transport protein (FATP)-1. Overexpression of FABPpm in C2C12 myotubes increased fatty acid oxidation coupled with the elevated expression of genes related to fatty acid oxidation. These changes were not observed in FATP1-overexpressed myotubes.
Conclusions: Differences in the gene expression of fatty acid transporters may, at least in part, affect insulin sensitivity in IMCL-accumulated nonobese men.

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PARK2/Parkin-mediated mitochondrial clearance contributes to the proteasome activation during slow-twitch muscle atrophy via NFE2L1 nuclear translocation

Norihiko Furuya, Shin-Ichi Ikeda, Shigeto Sato, Sanae Soma, Junji Ezaki, Juan Alejandro Oliva Trejo, Mitsue Takeda-Ezaki, Tsutomu Fujimura, Eri Arikawa-Hirasawa, Norihiro Tada, Masaaki Komatsu, Keiji Tanaka, Eiki Kominami, Nobutaka Hattori and Takashi Ueno

Autophagy （Autophagy） 10 （ 4 ） 631 - 641 2014年04月

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