FOOD - Biological functions and unique features on health

Daily consumption of one teaspoon of trehalose can help maintain glucose homeostasis: a double-blind, randomized controlled trial conducted in healthy volunteers

Chiyo Yoshizane, Akiko Mizote, Chikako Arai, Norie Arai, Rieko Ogawa, Shin Endo, Hitoshi Mitsuzumi & Shimpei Ushio

Background Trehalose is a natural disaccharide that is widely distributed. A previous study has shown that daily consumption of 10 g of trehalose improves glucose tolerance in individuals with signs of metabolic syndrome. In the present study, we determined whether a lower dose (3.3 g/day) of trehalose improves glucose tolerance in healthy Japanese volunteers. This was a randomized, double-blind, placebo-controlled study of healthy Japanese participants (n = 50). Each consumed 3.3 g ...

Nutr. J. 2020;19:68.

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Microglial autophagy–associated phagocytosis is essential for recovery from neuroinflammation

Rasmus Berglund, Andre Ortlieb Guerreiro-Cacais, Milena Z. Adzemovic, Manuel Zeitelhofer, Harald Lund, Ewoud Ewing, Sabrina Ruhrmann, Erik Nutma, Roham Parsa, Melanie Thessen-Hedreul, Sandra Amor, Robert A. Harris, Tomas Olsson and Maja Jagodic

Multiple sclerosis (MS) is a leading cause of incurable progressive disability in young adults caused by inflammation and neurodegeneration in the central nervous system (CNS). The capacity of microglia to clear tissue debris is essential for maintaining and restoring CNS homeostasis. This capacity diminishes with age, and age strongly associates with MS disease progression, although the underlying mechanisms are still largely elusive. Here, we demonstrate that the recovery ...

Sci. Immunol. 2020;5:eabb5077.

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CD8+ regulatory T cells are critical in prevention of autoimmune-mediated diabetes

Chikako Shimokawa, Tamotsu Kato, Tadashi Takeuchi, Noriyasu Ohshima, Takao Furuki, Yoshiaki Ohtsu, Kazutomo Suzue, Takashi Imai, Seiji Obi, Alex Olia, Takashi Izumi, Minoru Sakurai, Hirokazu Arakawa, Hiroshi Ohno & Hajime Hisaeda

Type 1 diabetes (T1D) is an autoimmune disease in which insulin-producing pancreatic β-cells are destroyed. Intestinal helminths can cause asymptomatic chronic and immunosuppressive infections and suppress disease in rodent models of T1D. However, the underlying regulatory mechanisms for this protection are unclear. Here, we report that CD8+ regulatory T (Treg) cells prevent the onset of streptozotocin -induced diabetes by a rodent intestinal nematode. Trehalose derived from nematodes affects the ...

Nat. Commun. 2020;11:1922.

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Trehalose itself plays a critical role on lipid metabolism: Trehalose increases jejunum cytoplasmic lipid droplets which negatively correlated with mesenteric adipocyte size in both HFD-fed trehalase KO and WT mice

Chikako Arai, Aki Suyama, Shigeyuki Arai, Norie Arai, Chiyo Yoshizane, Satomi Koya-Miyata, Akiko Mizote, Shin Endo, Toshio Ariyasu, Hitoshi Mitsuzumi & Shimpei Ushio

Background Trehalose is a functional disaccharide that has anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Trehalase hydrolyzes trehalose in the small intestine into two glucose molecules. In this study, we investigated whether trehalose can suppress adipocyte hypertrophy in mice in the presence or absence of trehalase. Trehalase knockout (KO) mice and wild-type (WT) mice were fed ...

Nutr. Metab. 2020;17:22.

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Continuous intake of Trehalose induces white adipose tissue Browning and Enhances energy metabolism

Chikako Arai, Norie Arai, Shigeyuki Arai, Chiyo Yoshizane, Satomi Miyata, Akiko Mizote, Aki Suyama, Shin Endo, Toshio Ariyasu, Hitoshi Mitsuzumi & Shimpei Ushio

Background Trehalose is well known as a functional disaccharide with anti-metabolic activities such as suppression of adipocyte hypertrophy in mice and alleviation of impaired glucose tolerance in humans. Recently, a new type of adipocyte beige cells, involved in so-called white adipocyte tissue (WAT) browning, has received much attention as a target for adaptive thermogenesis. To clarify the relationship between adipocyte hypertrophy suppression and beige cells involved in thermogenesis, ...

Nutr. Metab. 2020;16:45.

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Trehalose attenuates development of nonalcoholic steatohepatitis associated with type 2 diabetes in TSOD mouse

Kazutoshi Murotomi, Shigeyuki Arai, Aki Suyama, Akira Harashima, Yoshihiro Nakajima

Trehalose, a non-reducing disaccharide, induces autophagy. Trehalose mitigates insulin resistance and adipocyte hypertrophy in obese mice; however, its effect on the development of nonalcoholic steatohepatitis (NASH) associated with type 2 diabetes remains unknown. In this study, we investigated the effect of trehalose on the development of NASH in the Tsumura Suzuki Obese Diabetes (TSOD) mouse, a metabolic syndrome model characterized by obesity, type 2 diabetes, and NASH. We ...

J. Funct. Foods. 2019;56:303-311.

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The Influence of Trehalose on Atherosclerosis and Hepatic Steatosis in Apolipoprotein E Knockout Mice

Aneta Stachowicz, Anna Wiśniewska, Katarzyna Kuś, Anna Kiepura, Anna Gębska, Mariusz Gajda, Magdalena Białas, Justyna Totoń-Żurańska, Kamila Stachyra, Maciej Suski, Jacek Jawień, Ryszard Korbut and Rafał Olszanecki

Atherosclerosis and nonalcoholic fatty liver disease (NAFLD) are frequent causes of death in the Western countries. Recently, it has been shown that autophagy dysfunction plays an important role in the pathogenesis of both atherosclerosis and NAFLD; thus, activators of autophagy might be useful for novel therapeutic interventions. Trehalose—a naturally occuring disaccharide present in plants, bacteria, fungi, insects, and certain types of shrimps—is a known inducer of autophagy. However, ...

Int. J. Mol. Sci. 2019;20:1552.

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Trehalose Improves Cognition in the Transgenic Tg2576 Mouse Model of Alzheimer’s Disease

Portbury, Stuart D., Hare, Dominic J., Sgambelloni, Charlotte, Perronnes, Kali, Portbury, Ashley J., Finkelstein, David I. & Adlard, Paul A.

This study assessed the therapeutic utility of the autophagy enhancing stable disaccharide trehalose in the Tg2576 transgenic mouse model of Alzheimer’s disease (AD) via an oral gavage of a 2% trehalose solution for 31 days. Furthermore, as AD is a neurodegenerative condition in which the transition metals, iron, copper, and zinc, are understood to be intricately involved in the cellular cascades leading to the defining pathologies of the ...

J. Alzheimers Dis. 2017;60:549–560.

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Exploiting macrophage autophagy-lysosomal biogenesis as a therapy for atherosclerosis

Ismail Sergin, Trent D. Evans, Xiangyu Zhang, Somashubhra Bhattacharya, Carl J. Stokes, Eric Song, Sahl Ali, Babak Dehestani, Karyn B. Holloway, Paul S. Micevych, Ali Javaheri, Jan R. Crowley, Andrea Ballabio, Joel D. Schilling, Slava Epelman, Conrad C. Weihl, Abhinav Diwan, Daping Fan, Mohamed A. Zayed & Babak Razani

Macrophages specialize in removing lipids and debris present in the atherosclerotic plaque. However, plaque progression renders macrophages unable to degrade exogenous atherogenic material and endogenous cargo including dysfunctional proteins and organelles. Here we show that a decline in the autophagy–lysosome system contributes to this as evidenced by a derangement in key autophagy markers in both mouse and human atherosclerotic plaques. By augmenting macrophage TFEB, the master transcriptional regulator ...

Nat. Commun. 2017;8:15750.

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Glycemic, insulinemic and incretin responses after oral trehalose ingestion in healthy subjects

Chiyo Yoshizane, Akiko Mizote, Mika Yamada, Norie Arai, Shigeyuki Arai, Kazuhiko Maruta, Hitoshi Mitsuzumi, Toshio Ariyasu, Shimpei Ushio & Shigeharu Fukuda

Background Trehalose is hydrolyzed by a specific intestinal brush-border disaccharidase (trehalase) into two glucose molecules. In animal studies, trehalose has been shown to prevent adipocyte hypertrophy and mitigate insulin resistance in mice fed a high-fat diet. Recently, we found that trehalose improved glucose tolerance in human subjects. However, the underlying metabolic responses after trehalose ingestion in humans are not well understood. Therefore, we examined the glycemic, insulinemic and ...

Nutr. J. 2017;16:9.

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Oral trehalose supplementation improves resistance artery endothelial function in healthy middle-aged and older adults

Rachelle E. Kaplon, Sierra D. Hill, Nina Z. Bispham, Jessica R. Santos-Parker, Molly J. Nowlan, Laura L. Snyder, Michel Chonchol, Thomas J. LaRocca, Matthew B. McQueen, Douglas R. Seals

We hypothesized that supplementation with trehalose, a disaccharide that reverses arterial aging in mice, would improve vascular function in middle-aged and older (MA/O) men and women. Thirty-two healthy adults aged 50-77 years consumed 100 g/day of trehalose (n=15) or maltose (n=17, isocaloric control) for 12 weeks (randomized, double-blind). In subjects with Δbody mass<2.3kg (5 lb.), resistance artery endothelial function, assessed by forearm blood flow to brachial artery infusion ...

Aging. 2016;8:1167-1183.

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