Faculty Profiles - HIGASHIDA Kazuhiko

Papers - HIGASHIDA Kazuhiko

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Interaction Between Sarcopenic Obesity and Nonlocomotive Physical Activity on the Risk of Depressive Symptoms in Community-Dwelling Older Adult Japanese Women Reviewed

Yu Osugi, Aiko Imai, Toshiyuki Kurihara, Keiko Kishigami, Kazuhiko Higashida, Kiyoshi Sanada

Journal of Aging and Physical Activity 17 1 - 17 2023.1

Inhibition of the mitochondrial respiratory chain reduces catecholamine‑stimulated lipolysis via increasing lactate production in 3T3‑L1 adipocytes Reviewed

Nodoka Takeuchi, Kazuhiko Higashida, Naoya Nakai

2023

Intermittent fasting reduces mouse body fat while maintaining muscle mass by regulating protein synthesis and autophagy Reviewed

Rikako Yoshii, Kazuhiko Higashida, Naoya Nakai

Nutrition 2023

Low-carbohydrate, high-fat diet, and running exercise influence bone parameters in old mice. International journal

Yuki Aikawa, Takenori Yamashita, Naoya Nakai, Kazuhiko Higashida

Journal of applied physiology (Bethesda, Md. : 1985) 132 ( 5 ) 1204 - 1212 2022.5

Language：English Publishing type：Research paper (scientific journal)

We examined the effects and interactions of a low-carbohydrate, high-fat (LCHF) diet and voluntary running exercise on bone in older mice. Male 19-mo-old mice were divided into four groups by diet (control vs. LCHF) and exercise (sedentary vs. voluntary running). The control diet was 55% carbohydrate, 23% protein, and 22% fat, and the LCHF diet was 10% carbohydrate, 33% protein, and 57% fat as percentages of calories. The experiment ended when the mice reached 24 mo old. Statistical analysis was conducted using two-way analysis of variance with diet and exercise. The LCHF diet decreased bone mineral content (BMC), bone mineral density, bone volume fraction, and trabecular number. There was no significant interaction between diet and exercise on many bone parameters. However, there were significant diet and exercise interactions on lumbar BMC and tibial trabecular total tissue volume and average cortical thickness. The LCHF diet attenuated the benefit of running exercise on lumbar BMC and caused running to have a negative effect on tibial trabecular total tissue volume. Our study suggests that the LCHF diet impairs bone mass and some trabecular microstructure and reduces the benefit of exercise on lumbar BMC in old mice.NEW & NOTEWORTHY An LCHF diet is used in treatment and prevention of diseases or improving exercise performance. However, some studies have shown that an LCHF diet diminishes bone in young rodents. Our study demonstrates that an LCHF diet impairs bone mass and some trabecular microstructure in old mice, which are similar to the previous studies using young rodents. Moreover, our study shows that an LCHF diet reduces the benefit of exercise on lumbar BMC in old mice.

DOI： 10.1152/japplphysiol.00789.2021

PubMed

BDK knockout skeletal muscle satellite cells exhibit enhanced protein translation initiation signal in response to BCAA in vitro Reviewed

Nakai N, Iida N, Kitai S, Shimomura Y, Kitaura Y, Higashida K

Biosci Biotechnol Biochem Zbac021 2022.2

c-Myc overexpression increases ribosome biogenesis and protein synthesis independent of mTORC1 activation in mouse skeletal muscle Reviewed

Mori T, Ato S, Knudsen JR, Henriquez-Olguin C, Li Z, Wakabayashi K, Suginohara T, Higashida K, Tamura Y, Nakazato K, Jensen TE, Ogasawara R.

Am J Physiol Endocrinol Metab 321 ( 4 ) 551 - 559 2021.10

Glucose enhances catecholamine-stimulated lipolysis via increased glycerol-3-phosphate synthesis in 3T3-L1 adipocytes and rat adipose tissue Reviewed

Takeuchi N, Higashida K, Li X, Nakai N.

Mol Biol Rep 48 ( 6 ) 6269 - 6276 2021.9

Basal and resistance exercise-induced increase in protein synthesis is impaired in skeletal muscle of iron-deficient rats

Kazuhiko Higashida, Sachika Inou, Nodoka Takeuchi, Satoru Ato, Riki Ogasawara, Naoya Nakai

Nutrition 111389 - 111389 2021.6

Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats Reviewed

Ogura Y, Kakehashi C, Yoshihara T, Kurosaka M, Kakigi R, Higashida K, Fujiwara SE, Akema T, Funabashi T.

Plos one 2020.10

Iron deficiency attenuates protein synthesis stimulated by branched-chain amino acids and insulin in myotubes. International journal

Kazuhiko Higashida, Sachika Inoue, Naoya Nakai

Biochemical and biophysical research communications 531 ( 2 ) 112 - 117 2020.10

Language：English Publishing type：Research paper (scientific journal)

Iron deficiency anemia indicates poor nutrition and is a public health problem. Iron deficiency is also associated with muscle weakness. However, the intracellular mechanisms by which iron deficiency induces muscle weakness are obscure. The purpose of the present study was to evaluate the effect of iron deficiency on protein synthesis in basal and branched-amino acids (BCAA)- and insulin-stimulated state in muscle cells. Differentiated C2C12 myotubes were incubated with an iron chelator, deferoxamine mesylate, and then stimulated with BCAA or insulin to activate protein synthesis. This iron deprivation resulted in a significant reduction in the abundance of iron-containing proteins, such as the mitochondrial complex 1 subunit protein, compared to control cells, but not of protein that does not contain iron, such as citrate synthase. Proteins involved in glucose utilization, such as glucose transpoter-1, hexokinase and AMP-activated protein kinase (AMPK), were upregulated under iron deficiency. Additionally, rates of BCAA- and insulin-stimulated protein synthesis, measured by puromycin incorporation, were lower in iron-deficient myotubes than in control cells. We suggest that low iron availability attenuates BCAA- and insulin-stimulated protein synthesis, possibly via activation of AMPK in myotubes. The present findings advance the understanding of the importance of iron to skeletal muscle protein synthesis and, thus, may contribute to the prevention of sarcopenia and frailty.

DOI： 10.1016/j.bbrc.2020.07.041

PubMed

Autophagy under glucose starvation enhances protein translation initiation in response to re-addition of glucose in C2C12 myotubes. International journal

Naoya Nakai, Saki Kitai, Noriko Iida, Sachika Inoue, Kazuhiko Higashida

FEBS open bio 10 ( 10 ) 2149 - 2156 2020.10

Language：English Publishing type：Research paper (scientific journal)

Proteolysis is known to play a crucial role in maintaining skeletal muscle mass and function. Autophagy is a conserved intracellular process for the bulk degradation of proteins in lysosomes. Although nutrient starvation is known to induce autophagy, the effect of nutrient repletion following starvation on the mTOR pathway-mediated protein translation remains unclear. In the present study, we examined the effect of glucose starvation on the initiation of protein translation in response to glucose re-addition in C2C12 myotubes. Glucose starvation decreased the phosphorylation of p70 S6 kinase (p70S6K), a bonafide marker for protein translation initiation. Following re-addition of glucose, phosphorylation of p70S6K markedly increased only in glucose-starved cells. Inhibiting autophagy using pharmacological inhibitors diminished the effect of glucose re-addition on the phosphorylation of p70S6K, whereas inhibition of the ubiquitin-proteasome system did not exert any effect. In conclusion, autophagy under glucose starvation partially accounts for the activation of translation initiation by re-addition of glucose.

DOI： 10.1002/2211-5463.12970

PubMed

Iron deficiency attenuates catecholamine-stimulated lipolysis via downregulation of lipolysis-related proteins and glucose utilization in 3T3-L1 adipocytes Reviewed International journal

Higashida K, Takeuchi N, Inoue N, Hashimoto T, Nakai N

Molecular Medicine Reports 2020.3

Application of Molecular Hydrogen as a Novel Antioxidant in Sports Science Reviewed

Kawamura T, Higashida K, Muraoka I

Oxidative Medicine and Cellular Longevity 2020.1

Induction of Autophagy and Changes in Cellular Metabolism in Glucose Starved C2C12 Myotubes Reviewed

Naoya Nakai, Saki Kitai, Noriko Iida, Sachika Inoue, Ken Nakata, Taro Murakami, Kazuhiko Higashida

J Nutr Sci Vitaminol (Tokyo) . 66 ( 1 ) 41 - 47 2020.1

Ketogenic diet feeding improves aerobic metabolism property in extensor digitorum longus muscle of sedentary male rats. International journal

Yuji Ogura, Chiaki Kakehashi, Toshinori Yoshihara, Mitsutoshi Kurosaka, Ryo Kakigi, Kazuhiko Higashida, Sei-Etsu Fujiwara, Tatsuo Akema, Toshiya Funabashi

PloS one 15 ( 10 ) e0241382 2020

Language：English Publishing type：Research paper (scientific journal)

Recent studies of the ketogenic diet, an extremely high-fat diet with extremely low carbohydrates, suggest that it changes the energy metabolism properties of skeletal muscle. However, ketogenic diet effects on muscle metabolic characteristics are diverse and sometimes countervailing. Furthermore, ketogenic diet effects on skeletal muscle performance are unknown. After male Wistar rats (8 weeks of age) were assigned randomly to a control group (CON) and a ketogenic diet group (KD), they were fed for 4 weeks respectively with a control diet (10% fat, 10% protein, 80% carbohydrate) and a ketogenic diet (90% fat, 10% protein, 0% carbohydrate). After the 4-week feeding period, the extensor digitorum longus (EDL) muscle was evaluated ex vivo for twitch force, tetanic force, and fatigue. We also analyzed the myosin heavy chain composition, protein expression of metabolic enzymes and regulatory factors, and citrate synthase activity. No significant difference was found between CON and KD in twitch or tetanic forces or muscle fatigue. However, the KD citrate synthase activity and the protein expression of Sema3A, citrate synthase, succinate dehydrogenase, cytochrome c oxidase subunit 4, and 3-hydroxyacyl-CoA dehydrogenase were significantly higher than those of CON. Moreover, a myosin heavy chain shift occurred from type IIb to IIx in KD. These results demonstrated that the 4-week ketogenic diet improves skeletal muscle aerobic capacity without obstructing muscle contractile function in sedentary male rats and suggest involvement of Sema3A in the myosin heavy chain shift of EDL muscle.

DOI： 10.1371/journal.pone.0241382

PubMed

A Lactate-based compound containing caffeine in addition to voluntary running exercise decreases subcutaneous fat mass and improves glucose metabolism in obese rats Reviewed

Hashimoto T, Yokokawa T, Narusawa R, Okada Y, Kawaguchi R, Higashida K

Journal of Functional Foods 56 84 - 91 2019.3

Low-carbohydrate high-protein diet diminishes the insulin response to glucose load via suppression of SGLT-1 in mice. International journal

Kazuhiko Higashida, Shin Terada, Xi Li, Sachika Inoue, Noriko Iida, Saki Kitai, Naoya Nakai

Bioscience, biotechnology, and biochemistry 83 ( 2 ) 365 - 371 2019.2

Language：English Publishing type：Research paper (scientific journal)

The purpose of this study was to examine the effects of a low-carbohydrate high-protein (LCHP) diet on the expression of glucose transporters and their relationships to glucose metabolism. Male C57BL/6 mice were fed a normal control or LCHP diet for 2 weeks. An oral glucose tolerance test and insulin tolerance test (ITT) were performed, and the expression of glucose transporters was determined in the gastrocnemius muscle, jejunum and pancreas. The increase in plasma insulin concentrations after glucose administration was reduced in the LCHP group. However, LCHP diet had no effects on peripheral insulin sensitivity or glucose transporters expression in the gastrocnemius and pancreas. Soluble glucose transporter (SGLT)-1 protein content in jejunum was lower in the LCHP group. Taken together, these results suggest that the blunted insulin response after glucose administration in LCHP diet-fed mice might be due to decreased SGLT-1 expression, but not to an increase in peripheral insulin sensitivity. Abbreviations: LCHP: low-carbohydrate high-protein; ITT: insulin tolerance test; GLUT: glucose transporter; SGLT: soluble glucose transporter; OGTT: oral glucose tolerance test; AUC: area under the curve.

DOI： 10.1080/09168451.2018.1533803

PubMed

Time Course of Decrease in Skeletal Muscle Mitochondrial Biogenesis after Discontinuation of High-Fat Diet.

Li X, Higashida K, Kawamura T, Higuchi M

J Nutr Sci Vitaminol (Tokyo) 2018.6

Effects of exhaustive exercises, with different intensities, on oxidative stress markers in rat plasma and skeletal muscle Reviewed

Kawamura T, Fujii R, Li X, Higashida K, Muraoka I

Science and Sports 33 ( 3 ) 169 - 175 2018.6

Language：English Publishing type：Research paper (scientific journal) Publisher：Elsevier Masson SAS

Objectives: The purpose of this study was to examine the effects of exhaustive exercises, with different intensities, on oxidative stress markers in rat plasma and skeletal muscle. Methods: Male Sprague-Dawley rats (n = 24) were randomly divided into the following four groups: control (CON), low-intensity exercise (LE), high-intensity interval exercise (HE) and incremental exercise (IE). The animals in the latter three groups performed exercises in which they ran until exhaustion as follows: Animals in the LE group ran at 20 m/min (6° graded)
the HE group ran at 40 m/min for 30 s (0° graded) with a rest interval of 60 s between each run
and the IE group ran at 15 m/min (6° graded), initially, with the running speed gradually increased by 5 m/min, every 10 min. Immediately following the exercise, a blood sample was drawn, and followed by the gastrocnemius muscle and liver were quickly removed. These samples were analysed for lactate concentration, oxidative stress markers, and glycogen contents. Results: Plasma oxidative stress markers in the LE and HE groups demonstrated no change, while plasma protein carbonyl (PC) levels and total antioxidant capacity (TAC) in the IE group were significantly increased compared with the CON group (P &lt
0.05). In contrast, all the oxidative stress markers, in the skeletal muscle of the three exercise groups, demonstrated no change compared with the CON group. Conclusion: Incremental exhaustive exercise elevates the plasma PC levels and TAC, but does not change skeletal muscle oxidative stress markers in rats.

DOI： 10.1016/j.scispo.2017.08.008

Scopus

Leucine supplementation after mechanical stimulation activates protein synthesis via L-type amino acid transporter 1 in vitro Reviewed International journal

Nakai N, Kawano F, Murakami T, Nakata K, Higashida K.

J Cell Biochem 119 ( 2 ) 2094 - 2101 2018.2

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Papers - HIGASHIDA Kazuhiko