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Regulatory mechanisms of the green alga Ulva lactuca oligosaccharide via the metabolomics and gut microbiome in diabetic mice.

ABSTRACT: Type 2 diabetes (T2D) has emerged as one of the most acute public health diseases of the present time, which increases with the population ageing. This study aimed to evaluate the hypoglycaemic activity of Ulva lactuca oligosaccharide (ULO) under ageing-related diabetes conditions in an animal model. The results demonstrated that ULO can promote hypoglycaemia and delay senescence as mediated via GLP-1/GLP-1R pathway to mobilize the intercommunication between the brain and gut. In addition, twenty-six different metabolites and eight different bacteria were screened in the brain and the gut, respectively. A network relationship displayed that all-trans-retinoic acid has positive relationships with Bifidobacterium and Streptococcus, suggesting that plays a potential key role in maintaining the hypoglycaemic and anti-ageing activities of ULO. Based on these findings, ULO might be an efficient therapy for restoring blood glucose metabolism and delaying brain senescence in elderly T2D patients.

SUBMITTER: Chen Y

PROVIDER: S-EPMC9294526 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature

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Regulatory mechanisms of the green alga Ulva lactuca oligosaccharide via the metabolomics and gut microbiome in diabetic mice.

Chen Yihan Y Wu Weihao W Ni Xiaoyu X Farag Mohamed A MA Capanoglu Esra E Zhao Chao C

Current research in food science 20220714

Type 2 diabetes (T2D) has emerged as one of the most acute public health diseases of the present time, which increases with the population ageing. This study aimed to evaluate the hypoglycaemic activity of Ulva lactuca oligosaccharide (ULO) under ageing-related diabetes conditions in an animal model. The results demonstrated that ULO can promote hypoglycaemia and delay senescence as mediated via GLP-1/GLP-1R pathway to mobilize the intercommunication between the brain and gut. In a ...[more]

PMID: 35865803

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Project description:Increased amounts of reactive oxygen species (ROS) have been implicated in many pathological conditions, including cancer. The major machinery that the cell employs to neutralize excess ROS is through the activation of the antioxidant-response element (ARE) that controls the activation of many phase II detoxification enzymes. The transcription factor that recognizes the ARE, Nrf2, can be activated by a variety of small molecules, most of which contain an α,β-unsaturated carbonyl system. In the pursuit of chemopreventive agents from marine organisms, we built, fractionated, and screened a library of 30 field-collected eukaryotic algae from Florida. An edible green alga, Ulva lactuca, yielded multiple active fractions by ARE-luciferase reporter assay. We isolated three monounsaturated fatty acid (MUFA) derivatives as active components, including a new keto-type C18 fatty acid (1), the corresponding shorter chain C16 acid (2), and an amide derivative (3) of the C18 acid. Their chemical structures were elucidated by NMR and mass spectrometry. All three contain the conjugated enone motif between C7 and C9, which is thought to be responsible for the ARE activity. Subsequent biological studies focused on 1, the most active and abundant ARE activator isolated. C18 acid 1 induced the expression of ARE-regulated cytoprotective genes, including NAD(P)H:quinone oxidoreductase 1, heme oxygenase 1, thioredoxin reductase 1, both subunits of the glutamate-cysteine ligase (catalytic subunit and modifier subunit), and the cystine/glutamate exchange transporter, in IMR-32 human neuroblastoma cells. Its cellular activity requires the presence of Nrf2 and PI3K function, based on RNA interference and pharmacological inhibitor studies, respectively. Treatment with 1 led only to Nrf2 activation, and not the increase in production of NRF2 mRNA. To test its ARE activity and cytoprotective potential in vivo, we treated mice with a single dose of a U. lactuca fraction that was enriched with 1, which showed ARE-activating effects similar to those observed in vitro. This could be owing to this fraction's ability to stabilize Nrf2 through inhibition of Keap1-mediated Nrf2 ubiquitination and the subsequent accumulation and nuclear translocation of Nrf2. The induction of many ARE-driven antioxidant genes in vivo and most prominently in the heart agreed with the commonly recognized cardioprotective properties of MUFAs. A significant increase in Nqo1 transcript levels was also found in other mouse tissues such as the brain, lung, and stomach. Collectively, this study provides new insight into why consumption of dietary seaweed may have health benefits, and the identified compounds add to the list of chemopreventive dietary unsaturated fatty acids.

Project description:IntroductionDiabetic cognitive impairment(DCI) presents as a central nervous complication of diabetes especially among aging population. Melatonin (MEL) is known for its antioxidant and anti-inflammation effects in neuroprotective aspects. Recent evidence has demonstrated that the gut microbiome plays a key role in DCI by modulating cognitive function through the gut-brain crosstalk. MEL has been shown to modulate gut microbiota composition in diabetic model. However, the underlying mechanism through which the gut microbiome contributes to DCI remains unclear. This study aims to investigate the effect and mechanism of MEL in attenuating DCI in relation to regulating the gut microbiome and metabolomics.MethodsCognitive and memory function were assessed by the Morris water maze test, histopathological assessment of brain tissues, and immunoblotting of neuroinflammation and apoptosis. The levels of serum tumor necrosis factor-α (TNF-α) and Interleukin-18 (IL-18) were measured by enzyme-linked immunoassays to reflect the circulatory inflammation level.16S rRNA microbiome sequencing analysis was performed on control mice(db-m group), diabetic mice(db-db group) and MEL-treated diabetic mice(db-dbMEL group). Gut metabolites changes were characterized using liquid chromatography tandem mass spectrometry (LC-MS/MS).ResultsOur study confirmed that MEL alleviated diabetes-induced cognition and memory dysfunction. MEL protected against neuroinflammation and apoptosis in hippocampus of db-db mice. MEL corrected the increased abundance of Bacteroides and Dorea and the reduced abundance of Prevotella in db-db mice. The vast majority of differential metabolites among the three groups were lipids and lipid-like molecules. MEL significantly restored the reduced levels of pyruvate and lactic acid.DiscussionOur results supported the use of MEL as a promising therapeutic agent for DCI, in which the underlying mechanism may be associated with gut microbiome and metabolomics regulation.

Dataset Information

Regulatory mechanisms of the green alga Ulva lactuca oligosaccharide via the metabolomics and gut microbiome in diabetic mice.

Publications

Regulatory mechanisms of the green alga <i>Ulva lactuca</i> oligosaccharide via the metabolomics and gut microbiome in diabetic mice.

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