Project description:In the present study, we investigated the consequences of trehalose intake on brain metabolism in mice drinking for 0, 1, and 10 days. Microarray analyses were performed to identify the molecular targets involved in the brain metabolism of trehalose intake.
Project description:The melanocortin system is a brain circuit that influences energy balance by regulating energy intake and expenditure. In addition, the brain-melanocortin system controls adipose tissue metabolism to optimize fuel mobilization and storage. Specifically, increased brain-melanocortin signaling or negative energy balance promotes lipid mobilization by increasing Sympathetic Nervous input to adipose tissue. In contrast, calorie-independent mechanisms favoring energy storage are less understood. Here we demonstrate that obesogenic signals, including reduction of brain-melanocortin signaling or high-fat feeding, actively promote fat mass gain independently of caloric intake via efferent nerve fibers conveyed by the common hepatic branch of the vagus nerve. These signals promote adipose tissue expansion by activating lipogenic program and adipocyte and endothelial cell proliferation independently of insulin action or the sympathetic tone to adipose tissue. These data reveal a novel physiological mechanism whereby the brain controls energy stores that may contribute to increased susceptibility to obesity.
Project description: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. 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.
Project description:Grapevine is an important economic fruit tree, and European grape (Vitis vinifera L.) has been widely used in fresh food, drying, winemaking and grape seed extract. However, most European grapes have low resistance to low temperature, drought and salt stress, and these abiotic stresses will limit the growth and development of grapes, thereby affecting the grape quality and yield. Many reports have shown that exogenous or endogenous trehalose can help improve plant stress resistance. Therefore, in order to investigate the function and molecular mechanism of trehalose metabolism in grape response to stress, this project was conducted.
Project description:Trehalose is the nonreducing disaccharide of glucose, evolutionarily conserved in invertebrates. The living skin equivalent (LSE) is an organotypic coculture containing keratinocytes cultivated on fibroblast-populated dermal substitutes. We demonstrated that human primary fibroblasts treated with highly concentrated trehalose promote significantly extensive spread of the epidermal layer of LSE without any deleterious effects. The RNA-seq analysis of trehalose-treated 2D and 3D fibroblasts at early time points revealed the involvement of the CDKN1A pathway, the knockdown of which significantly suppressed the upregulation of DPT, ANGPT2, VEGFA, EREG, and FGF2. The trehalose-treated fibroblasts were positive for senescence-associated β-galactosidase. Finally, transplantation of the dermal substitute with trehalose-treated fibroblasts accelerated wound closure and increased capillary formation significantly in the experimental mouse wounds in vivo, which was canceled by the CDKN1A knockdown. These data indicate that high-concentration trehalose can induce the senescence-like state in fibroblasts via CDKN1A/p21, which may be therapeutically useful for optimal wound repair.
Project description:Quantitative mass spectrometry reveals food intake-induced neuropeptide level change in rat brain and functional assessment of selected neuropeptides as feeding regulators
Project description:When mice of accelerated senescence prone 10 (SAMP10) were psychosocially stressed using male mouse’s territorial imperative, the mice exhibited higher cerebral atrophy and cognitive dysfunction than same-aged group-housing mice. The brain atrophy was examined using MRI. The volumes of various brain areas were decreased at the time of one month after confrontational housing. However, in SAMP10 mice ingesting theanine, the main amino acid in tea leaves, brain atrophy was suppressed even under confrontational housing. To investigate the function of theanine, the early response against stress was examined at the third day of confrontational housing. The level of transcription factor Npas4 that plays a role in the development of inhibitory synapses for regulating the balance between excitation and suppression was significantly increased by theanine intake. Actually, the levels of glutamate and γ-aminobutyric acid (GABA), excitatory and inhibitory neurotransmitters, were balanced in the mice ingested theanine under confrontational housing. These data suggest that theanine suppresses stress-induced damage in the brain via increased expression of Npas4 and regulation of excitement/suppression balance. In addition, SAMP10 is a useful model of stress vulnerability.
Project description:The otsB2 gene encoding trehalose-6-phosphate phosphatase is essential for in vitro growth of Mycobacterium tuberculosis and required to establish an acute infection in mice. Essentiality of otsB2 is due to direct or indirect toxic effects associated with the substrate trehalose-6-phosphate that accumulates when OtsB2 gene expression is impaired. In order to gain insight into the molecular basis of trehalose-6-phosphate mediated toxic effects, whole genome transcriptome profiling was done using RNA-seq. A conditional otsB2 mutant of Mycobacterium tuberculosis was generated by inserting an anhydrotetracycline-inducible promoter cassette upstream of the otsB2 start codon,and the transcriptome profile of a fully induced mutant resembling the wildtype phenotype was compared to that of a partially silenced mutant under conditions where 30% residual growth relative to the fully induced mutant was observed.
Project description:Streptococcus mutans, the organism most frequently associated with the development of dental caries, is able to utilize a diverse array of carbohydrates for energy metabolism. One such molecule is trehalose, a disaccharide common in human foods, which has recently been implicated in enhancing the virulence of epidemic strains of the pathogen, Clostridium difficile. In this study, deletion mutants of all three genes in the putative S. mutans trehalose utilization operon were characterized and shown to be required for wild-type levels of growth when trehalose was the only carbohydrate source provided. Interestingly, the TreR transcriptional regulator appeared to be critical for responding to oxidative stress, and for mounting a protective stress tolerance response following growth at moderately acidic pH. RNAseq of a treR deletion mutant suggested that in S. mutans, TreR acts as a trehalose-sensing activator of transcription of the tre operon, rather than a repressor, as described in other species. In addition, deletion of treR caused the down-regulation of a number of genes involved in genetic competence and bacteriocin production, supporting results of a recent study linking trehalose and the S. mutans competence pathways. Finally, deletion of treR compromised the ability of S. mutans to inhibit the growth of the competing species, Streptococcus gordonii and Lactococcus lactis. Taken together, this study solidifies the role of the S. mutans tre operon in trehalose utilization and suggests novel functions for the TreR regulator, including roles in stress response and competitive fitness.