Trehalose

Background: Aging is associated with chronic diseases and increased oxidative stress, particularly affecting liver function. Aging is linked to chronic diseases and heightened oxidative stress, particularly impacting liver function. Recent research has demonstrated that oral administration of trehalose offers multiple benefits for various tissues and organs.Methods: This study investigated the effects of oral trehalose (2% in water) on the gene expression of key markers linked to liver oxidative stress and inflammation in 4-month-old adult and 24-month-old Wistar rats. Thirty-two male Wistar rats (n = 8) were randomly assigned into four groups: adult control, aged control, adult trehalose (2% in water), and aged trehalose, over a treatment period of one month. Following treatment, liver tissues were analyzed using real-time PCR for genes related to oxidative stress (PGC-1α, NRF2, and SOD) and inflammation (NF-κB, IL-1β, TNF-α, and TGF-β).Results: Our findings revealed a significant up-regulation of PGC-1α, NRF2, and SOD in aged trehalose group compared to the aged control (P < 0.001); however, SOD expression increased by trehalose administration in aged rats compared to other 3 groups. Inflammatory markers (NF-κB, IL-1β, TNF-α) were significantly reduced by trehalose, and TGF-β expression, involved in fibrosis, was attenuated exclusively in aged rats compared with controls (P < 0.05).Conclusion: These results suggest that trehalose has a protective effect on hepatic function, particularly in the aging population, and highlight its potential therapeutic role in age-associated liver dysfunction.

As the fourth-largest global food crop, the quality and functional characteristics of processed potato products are closely linked to endogenous sugar metabolism in tubers, with the trehalose–sucrose metabolism playing a key role in processing adaptability. This study analyzed 333 accessions from a tetraploid potato natural population. The trehalose and sucrose content of potato tubers at harvest was quantified using the high-performance liquid chromatography (HPLC) method. Combined with whole-genome resequencing, a genome-wide association study (GWAS) was conducted to map regulatory loci and identify candidate genes. The results showed that relative trehalose content in tubers was 20.38–24.78, while relative sucrose content was 10.32–19.50. Frequency histograms for both sugars exhibited normal distributions characteristic of quantitative traits, and a positive correlation was observed between them. GWAS for trehalose identified 111 significant SNP loci, mainly on chromosomes 10 and 12, leading to the identification of 88 candidate genes. Kyoto encyclopedia of genes and genomes analysis (KEGG) revealed that trehalose-related genes were primarily involved in pathways such as ABC transporters, tricarboxylic acid (TCA) cycle, and cysteine and methionine metabolism. Candidate genes potentially regulating tuber trehalose content included GH10, GH28, GH127, UXS, UGT, PMEI, and MYB108. For sucrose, GWAS identified 279 significant SNP loci, mainly on chromosomes 5, 6, and 12, resulting in 111 candidate genes. KEGG enrichment analysis showed that sucrose-related genes were enriched in pathways including starch and sucrose metabolism, cyanoamino acid metabolism, and phenylpropanoid biosynthesis. Candidate genes potentially regulating tuber sucrose content included GH17, GH31,GH47, GH9A4, SPP1, BGLU12, GSA1, TPS8, cwINV4, HXK, UST, MYB5, MYB14, and WRKY11. Therefore, this study provides marker loci for trehalose and sucrose metabolism research, aiming to clarify their regulatory mechanisms and support potato variety improvement and superior germplasm development.

Mucopolysaccharidosis type II (MPS II) is caused by a deficiency in iduronate-2-sulfatase (Ids), an enzyme that catabolizes glycosaminoglycan (GAG). Ids insufficiency results in the accumulation of GAG in various organs, ultimately resulting in multisystemic disease. Trehalose, a non-reducing disaccharide, has shown protective effects against various diseases. However, its potential utility through oral administration in MPS II has not yet been explored. In the present study, to investigate the efficacy of oral trehalose in Ids-knock-out (KO) mice, Ids-KO and wild type (WT) mice were treated with 2% trehalose dissolved in distilled water ad libitum for 24&nbsp;weeks. Histological analysis revealed that almost all tissues from Ids-KO mice exhibited abnormal changes, including large vacuolization, inflammatory cell infiltration, and GAG deposition. However, oral administration of trehalose significantly suppressed GAG levels, vacuolization, inflammation and apoptosis in the spleen and brain. Additionally, oral trehalose considerably improved cognitive functions, such as short-term spatial learning and working memory, alongside limited improvements in walking capacity in Ids-KO mice. These results suggest that oral trehalose can reduce GAG accumulation, vacuolization and the number of apoptotic and inflammatory cells in pathological tissues including the brain, ultimately considerably improving spontaneous alteration behavior and could be a promising treatment option for MPS II.

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic lipid deposition, is one of the most prevalent chronic metabolic disorders globally, and its pharmaceutical treatments are still limited. Excessive lipid accumulation triggers endoplasmic reticulum (ER) stress and autophagy flux dysf …

Nonalcoholic fatty liver disease (NAFLD), characterized by hepatic lipid deposition, is one of the most prevalent chronic metabolic disorders globally, and its pharmaceutical treatments are still limited. Excessive lipid accumulation triggers endoplasmic reticulum (ER) stress and autophagy flux dysfunction, which are important mechanisms for NAFLD. Trehalose (Tre), a natural disaccharide, has been identified to reduce hepatic steatosis and glucose intolerance. However, its underlying mechanisms for NAFLD remain unclear. In this study, a high-fat-diet (HFD)-induced mouse NAFLD model and a saturated fatty acid palmitic acid (PA)-stimulated cell model were constructed. The results indicated that Tre supplementation ameliorated hepatocyte lipid deposition in vitro, as well as hepatic steatosis and hyperlipidemia in vivo. Mechanistically, Tre alleviated both autophagy flux dysfunction and endoplasmic reticulum (ER) stress. Under the stimulation of HFD or PA, Tre remarkably increased the expression and nucleic translocation of the lysosomal master protein transcription factor EB (TFEB), while decreasing the accumulation of p62 and also decreasing the ER stress markers (inositol-requiring enzyme 1 (IRE1α), XBP-1, CHOP, and BIP). Similar results were observed in an ER stressor tunicamycin (TM)-induced in vivo and in vitro models. In addition, the transcriptomic analysis of NAFLD patients revealed significant differences in ER stress-related and autophagy-related biomarkers, including TFEB, ATG7, IRE1α, and CHOP. Molecular docking results demonstrated a strong affinity between Tre and both IRE1α and TFEB. Overall, Tre protected hepatocytes from lipotoxicity-related ER stress and autophagy dysfunction, and its regulatory effect on the IRE1α–TFEB signaling pathway may be a critical mechanism. These findings suggest that Tre, as a bioactive substance with significant medicinal potential, holds considerable promise for drug development and clinical application in treating NAFLD.

For over forty years, a sugar of rare configuration known as trehalose (two molecules of glucose linked at their 1-carbons), has been recognised for m…

Background: Osteoporosis, a prevalent bone metabolic disease, often requires long-term drug treatments that may lead to serious side effects. Trehalose, a natural disaccharide found in various organisms, has been shown to have a promoting effect on autophagy. However, whether trehalose can improve bone mass recovery in ovariectomized rats and its underlying mechanisms remains unclear. In this study, trehalose was administered to ovariectomized rats to evaluate its therapeutic potential for osteoporosis following ovariectomy. Methods: Micro-computed tomography (Micro-CT), hematoxylin and eosin (HE) and immunohistochemical staining techniques were utilized to evaluate the impact of trehalose on osteoporosis induced by ovariectomy (OVX) in mice, both in imaging and histological dimensions. Furthermore, the influence of trehalose on osteoblastogenesis and functional activity was quantified through Alizarin Red S (ARS) staining and immunoblotting assays. Results: Trehalose effectively mitigated bone loss, elevated autophagy and suppressed pyroptosis in ovariectomized rats. Furthermore, 3-methyladenine diminished the protective effects of trehalose, particularly in promoting autophagy and inhibiting pyroptosis. Conclusions: Trehalose demonstrates significant potential in treating osteoporosis by suppressing NLRP3 inflammasome-driven pyroptosis, primarily through autophagy promotion. This suggests that trehalose could be a promising, safer alternative treatment for osteoporosis.

Trehalose (α-d-glucopyranosyl-(1-1)-α-D-glucopyranoside) has found applications in diverse food products as a sweetener, stabilizer, and humectant. Recent attention has focused on trehalose due to its contradictory effects on the virulence of Clostridium difficile. In this study, we investigate the …

Improvements in health-related quality of life and serum biomarkers (GAGs, liver aminotransferase levels, antioxidant status), as well as liver and spleen size, were found following 3 months of trehalose administration in patients with MPS IIIA and MPS IIIB.

Trehalose (α-d-glucopyranosyl-(1–1)-α-D-glucopyranoside) has found applications in diverse food products as a sweetener, stabilizer, and humectant. Re…

Trehalose, a remarkable substance, holds great importance in biomedicine for its anti-inflammatory properties and its capacity to hinder scar formatio…

Trehalose metabolism variants are common in C. difficile. Increases in total dietary trehalose during the early-mid 2000s C. difficile epidemic were likely relatively minimal. Alternative explanations are required to explain why ribotype-027, ribotype-078 and ribotype-017 have been successful.

Abstract. In a case–control study of patients with Clostridium difficile infection, we found no statistically significant association between the presence of tr

Myocardial ischemia/reperfusion (I/R) injury is a pathological damage secondary to myocardial ischemia that can further aggravate tissue and organ injuries. Therefore, there is an urgent need to develop an effective approach for alleviating myocardial I/R injury. Trehalose (TRE) is a natural bioacti …

Introduction: Atherosclerosis is a chronic inflammatory disease caused by the deposition of lipids within the artery wall. During atherogenesis, efficient autophagy is needed to facilitate efferocytosis and cholesterol efflux, limit inflammation and lipid droplet buildup, and eliminate defective mitochondria and protein aggregates. Central to the regulation of autophagy is the transcription factor EB (TFEB), which coordinates the expression of lysosomal biogenesis and autophagy genes. In recent years, trehalose has been shown to promote TFEB activation and protect against atherogenesis. Here, we sought to investigate the role of autophagy activation during atherosclerosis regression. Methods and Results: Atherosclerosis was established in C57BL/6N mice by injecting AAV-PCSK9 and 16 weeks of Western diet feeding, followed by switching to a chow diet to induce atherosclerosis regression. During the regression period, mice were either injected with trehalose concomitant with trehalose supplementation in their drinking water or injected with saline for 6 weeks. Female mice receiving trehalose had reduced atherosclerosis burden, as evidenced by reduced plaque lipid content, macrophage numbers and IL-1b content in parallel with increased plaque collagen deposition, which was not observed in their male counterparts. In addition, trehalose-treated female mice had lower levels of circulating leukocytes, including inflammatory monocytes and CD4 + T cells. Lastly, we found that autop...

TBI is a major global health issue due to its high morbidity and mortality rates. Persistent neurodegeneration following secondary brain injuries is a…

Atherosclerosis, cholesterol-driven plaque formation in arteries, is a complex multicellular disease which is a leading cause of vascular diseases. During the progression of atherosclerosis, the autophagic function is impaired, resulting in lipid accumulation-mediated foam cell formation. The stimulation of autophagy is crucial for the recovery of cellular recycling process. One of the potential autophagy inducers is trehalose, a naturally occurring non-reducing disaccharide. However, trehalose has poor bioavailability due to its hydrophilic nature which results in poor penetration through cell membranes. To enhance its bioavailability, we developed trehalose-releasing nanogels (TNG) for the treatment of atherosclerosis. The nanogels were fabricated through copolymerization of 6-O-acryloyl-trehalose with the selected acrylamide-type monomers affording a high trehalose conjugation (~ 58%, w/w). TNG showed a relatively small hydrodynamic diameter (dH, 67 nm) and a uniform spherical shape and were characterized by negative ζ potential (-18 mV). Thanks to the trehalose-rich content, TNG demonstrated excellent colloidal stability in biological media containing serum and were non-hemolytic to red blood cells. In vitro study confirmed that TNG could stimulate autophagy in foam cells and enhance lipid efflux and in vivo study in ApoE−/− mice indicated a significant reduction in atherosclerotic plaques, while increasing autophagic markers. In conclusion, TNG hold great promise as a trehalose delivery system to restore impaired autophagy-mediated lipid efflux in atherosclerosis and subsequently reduce atherosclerotic plaques. Graphical abstract

Saccharides are a popular group of stabilizers in liquid, frozen and freeze dried protein formulations. The current work reviewed the stabilization me…

Trehalose (Tre) is a non-reducing disaccharide found in many species, including bacteria, fungi, invertebrates, yeast, and even plants, where it acts …

Ralstonia solanacearum causes bacterial wilt disease, leading to severe crop losses. Xylem sap from R. solanacearum-infected tomato is enriched in the disaccharide trehalose. Water-stressed plants also accumulate trehalose, which increases drought tolerance via abscisic acid (ABA) signaling. Because R. solanacearum-infected plants suffer reduced water flow, we hypothesized that bacterial wilt physiologically mimics drought stress, which trehalose could mitigate. We found that R. solanacearum-infected plants differentially expressed drought-associated genes, including those involved in ABA and trehalose metabolism, and had more ABA in xylem sap. Consistent with this, treating tomato roots with ABA reduced both stomatal conductance and stem colonization by R. solanacearum. Treating roots with trehalose increased xylem sap ABA and reduced plant water use by lowering stomatal conductance and temporarily improving water use efficiency. Trehalose treatment also upregulated expression of salicylic acid (SA)-dependent tomato defense genes; increased xylem sap levels of SA and other antimicrobial compounds; and increased bacterial wilt resistance of SA-insensitive NahG tomato plants. Additionally, trehalose treatment increased xylem concentrations of jasmonic acid and related oxylipins. Finally, trehalose-treated plants were substantially more resistant to bacterial wilt disease. Together, these data show that exogenous trehalose reduced both water stress and bacterial wilt disease and triggered systemic disease resistance, possibly through a Damage Associated Molecular Pattern (DAMP) response pathway. This suite of responses revealed unexpected linkages between plant responses to biotic and abiotic stress and suggested that R. solanacearum-infected plants increase trehalose to improve water use efficiency and increase wilt disease resistance. The pathogen may degrade trehalose to counter these efforts. Together, these results suggest that treating tomatoes with exogenous trehalose could be a practical strategy for bacterial wilt management.

From the Department of Medico-Surgical Sciences and Biotechnologies, Sapienza University of Rome, Latina, Italy (G.F., S.S.)

Clostridioides difficile , the leading cause of antibiotic-associated diarrhoea worldwide, is a genetically diverse species which can metabolise a number of nutrient sources upon colonising a dysbiotic gut environment. Trehalose, a disaccharide sugar consisting of two glucose molecules bonded by an α 1,1-glycosidic bond, has been hypothesised to be involved in the emergence of C. difficile hypervirulence due to its increased utilisation by the RT027 and RT078 strains. Here, growth in trehalose as the sole carbon source was shown to be non-uniform across representative C. difficile strains, even though the genes for its metabolism were induced. Growth in trehalose reduced the expression of genes associated with toxin production and sporulation in the C. difficile R20291 (RT027) and M120 (RT078) strains in vitro, suggesting an inhibitory effect on virulence factors. Interestingly, the R20291 TreR transcriptional regulatory protein appeared to possess an activator function as its DNA-binding ability was increased in the presence of its effector, trehalose-6-phosphate. Using RNA-sequencing analysis, we report the identification of a putative trehalose metabolism pathway which is induced during growth in trehalose: this has not been previously described within the C. difficile species. These data demonstrate the metabolic diversity exhibited by C. difficile which warrants further investigation to elucidate the molecular basis of trehalose metabolism within this important gut pathogen.

DARU Journal of Pharmaceutical Sciences - Trehalose is a non-reducing disaccharide synthesized by lower organisms. It has recently received special attention because of its neuroprotective...

Trehalose significantly abates myocardial hypertrophy and pressure overload-induced cardiomyocyte apoptosis in mice. The cardioprotective effect of trehalose on enhanced autophagy is attributed, at least in part, to the promotion of autophagic degradation of GATA4.