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Nutrients Jun 2024High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and...
BACKGROUND
High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated. The aim of the study was to test whether the sucrose-free cocoa butter-based high-fat diet (C-HFD) feeding in mice leads to gut dysbiosis that associates with a pathologic phenotype marked by hepatic steatosis, low-grade inflammation, perturbed glucose homeostasis, and insulin resistance, compared with control mice fed the fish oil based high-fat diet (F-HFD).
RESULTS
C57BL/6 mice (5-6 mice/group) were fed two types of high fat diets (C-HFD and F-HFD) for 24 weeks. No significant difference was found in the liver weight or total body weight between the two groups. The 16S rRNA sequencing of gut bacterial samples displayed gut dysbiosis in C-HFD group, with differentially-altered microbial diversity or relative abundances. , and were highly abundant in C-HFD group, while the , (TM7), , and were more abundant in F-HFD group. Other taxa in C-HFD group included the (AF12), and An increased Firmicutes/Bacteroidetes (F/B) ratio in C-HFD group, compared with F-HFD group, indicated the gut dysbiosis. These gut bacterial changes in C-HFD group had predicted associations with fatty liver disease and with lipogenic, inflammatory, glucose metabolic, and insulin signaling pathways. Consistent with its microbiome shift, the C-HFD group showed hepatic inflammation and steatosis, high fasting blood glucose, insulin resistance, increased hepatic de novo lipogenesis (Acetyl CoA carboxylases 1 (), Fatty acid synthase (), Stearoyl-CoA desaturase-1 (), Elongation of long-chain fatty acids family member 6 (), Peroxisome proliferator-activated receptor-gamma () and cholesterol synthesis (β-(hydroxy β-methylglutaryl-CoA reductase (). Non-significant differences were observed regarding fatty acid uptake (Cluster of differentiation 36 (), Fatty acid binding protein-1 () and efflux (ATP-binding cassette G1 (), Microsomal TG transfer protein () in C-HFD group, compared with F-HFD group. The C-HFD group also displayed increased gene expression of inflammatory markers including Tumor necrosis factor alpha (), C-C motif chemokine ligand 2 (), and Interleukin-12 (), as well as a tendency for liver fibrosis.
CONCLUSION
These findings suggest that the sucrose-free C-HFD feeding in mice induces gut dysbiosis which associates with liver inflammation, steatosis, glucose intolerance and insulin resistance.
Topics: Animals; Dysbiosis; Gastrointestinal Microbiome; Insulin Resistance; Diet, High-Fat; Mice, Inbred C57BL; Male; Mice; Fatty Liver; Liver; Dietary Fats; Sucrose
PubMed: 38931284
DOI: 10.3390/nu16121929 -
Microorganisms Jun 2024The enzymatic hydrolysis of the non-reducing disaccharide trehalose in yeasts is carried out by trehalase, a highly specific α-glucosidase. Two types of such trehalase...
The enzymatic hydrolysis of the non-reducing disaccharide trehalose in yeasts is carried out by trehalase, a highly specific α-glucosidase. Two types of such trehalase activity are present in yeasts, and are referred to as neutral and acid enzymes. They are encoded by distinct genes ( and , respectively) and exhibit strong differences in their biochemical and physiological properties as well as different subcellular location and regulatory mechanisms. Whereas a single gene codes for acid trehalase, the genome of some yeasts appears to predict the existence of a second redundant neutral trehalase, encoded by the gene, a paralog of . In the corresponding two proteins share 77% amino acid identity, leading to the suggestion that codes for a functional trehalase activity. However, Nth2p lacks any measurable neutral trehalase activity and disruption of gene has no effect on this activity compared to a parental strain. Likewise, single nth1Δ and double nth1Δ/nth2Δ null mutants display no detectable neutral activity. Furthermore, disruption of does not cause any apparent phenotype apart from a slight involvement in thermotolerance. To date, no evidence of a duplicated NTH gene has been recorded in other archetypical yeasts, like or , and a possible regulatory mechanism of Nth2p remains unknown. Therefore, although genomic analysis points to the existence, in some yeasts, of two distinct genes encoding trehalase activities, the large body of biochemical and physiological evidence gathered from gene does not support this proposal. Indeed, much more experimental evidence would be necessary to firmly validate this hypothesis.
PubMed: 38930613
DOI: 10.3390/microorganisms12061232 -
Children (Basel, Switzerland) Jun 2024Bothersome gastrointestinal (GI) signs/symptoms, including abdominal pain, distension, nausea, and flatulence, are common in children. A diet low in fermentable...
Bothersome gastrointestinal (GI) signs/symptoms, including abdominal pain, distension, nausea, and flatulence, are common in children. A diet low in fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) is frequently recommended for children with GI symptoms. Currently, there are no studies on the effect of FODMAPs in healthy schoolchildren. In this cross-sectional study, schoolchildren reported an association between FODMAPs and GI symptoms through a standardized questionnaire and images of 20 common staples known to be rich in FODMAPs. A total of 208 schoolchildren aged 8-18 years old participated. A proportion of 38.0% of children reported GI symptoms, with abdominal pain (33%) being the most common complaint followed by abdominal distension (24%) and nausea (23%). The majority of children who reported intolerances to FODMAP-containing foods were intolerant to less than two food groups (76%). While vegetables and legumes (26%), particularly black beans (11%) and onions (7%), emerged as the most common group of triggers, milk (12%) stood out as the single food most frequently associated with GI symptoms. In conclusion, there was a high prevalence of FODMAPs intolerance among schoolchildren. Larger studies are recommended to confirm these findings and to inform possible dietary interventions to reduce the effect of FODMAPs on schoolchildren.
PubMed: 38929321
DOI: 10.3390/children11060742 -
International Journal of Molecular... Jun 2024The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), to various cell surface glycoproteins and has been...
The beta-galactoside-binding mammalian lectin galectin-1 can bind, via its carbohydrate recognition domain (CRD), to various cell surface glycoproteins and has been implicated in a range of cancers. As a consequence of binding to sugar residues on cell surface receptors, it has been shown to have a pleiotropic effect across many cell types and mechanisms, resulting in immune system modulation and cancer progression. As a result, it has started to become a therapeutic target for both small and large molecules. In previous studies, we used fluorescence polarization (FP) assays to determine values to screen and triage small molecule glycomimetics that bind to the galectin-1 CRD. In this study, surface plasmon resonance (SPR) was used to compare human and mouse galectin-1 affinity measures with FP, as SPR has not been applied for compound screening against this galectin. Binding affinities for a selection of mono- and di-saccharides covering a 1000-fold range correlated well between FP and SPR assay formats for both human and mouse galectin-1. It was shown that slower dissociation drove the increased affinity at human galectin-1, whilst faster association was responsible for the effects in mouse galectin-1. This study demonstrates that SPR is a sound alternative to FP for early drug discovery screening and determining affinity estimates. Consequently, it also allows association and dissociation constants to be measured in a high-throughput manner for small molecule galectin-1 inhibitors.
Topics: Galectin 1; Surface Plasmon Resonance; Humans; Animals; Mice; Kinetics; Protein Binding; Small Molecule Libraries; Fluorescence Polarization
PubMed: 38928409
DOI: 10.3390/ijms25126704 -
International Journal of Molecular... Jun 2024Hydrogen sulfide (HS) is a novel gasotransmitter. Sucrose (SUC) is a source of cellular energy and a signaling molecule. Maize is the third most common food crop...
Hydrogen sulfide (HS) is a novel gasotransmitter. Sucrose (SUC) is a source of cellular energy and a signaling molecule. Maize is the third most common food crop worldwide. However, the interaction of HS and SUC in maize thermotolerance is not widely known. In this study, using maize seedlings as materials, the metabolic and functional interactions of HS and SUC in maize thermotolerance were investigated. The data show that under heat stress, the survival rate and tissue viability were increased by exogenous SUC, while the malondialdehyde content and electrolyte leakage were reduced by SUC, indicating SUC could increase maize thermotolerance. Also, SUC-promoted thermotolerance was enhanced by HS, while separately weakened by an inhibitor (propargylglycine) and a scavenger (hypotaurine) of HS and a SUC-transport inhibitor (N-ethylmaleimide), suggesting the interaction of HS and SUC in the development of maize thermotolerance. To establish the underlying mechanism of HS-SUC interaction-promoted thermotolerance, redox parameters in mesocotyls of maize seedlings were measured before and after heat stress. The data indicate that the activity and gene expression of HS-metabolizing enzymes were up-regulated by SUC, whereas HS had no significant effect on the activity and gene expression of SUC-metabolizing enzymes. In addition, the activity and gene expression of catalase, glutathione reductase, ascorbate peroxidase, peroxidase, dehydroascorbate reductase, monodehydroascorbate reductase, and superoxide dismutase were reinforced by HS, SUC, and their combination under non-heat and heat conditions to varying degrees. Similarly, the content of ascorbic acid, flavone, carotenoid, and polyphenol was increased by HS, SUC, and their combination, whereas the production of superoxide radicals and the hydrogen peroxide level were impaired by these treatments to different extents. These results imply that the metabolic and functional interactions of HS and sucrose signaling exist in the formation of maize thermotolerance through redox homeodynamics. This finding lays the theoretical basis for developing climate-resistant maize crops and improving food security.
Topics: Zea mays; Hydrogen Sulfide; Oxidation-Reduction; Thermotolerance; Sucrose; Gene Expression Regulation, Plant; Heat-Shock Response; Seedlings; Plant Proteins
PubMed: 38928304
DOI: 10.3390/ijms25126598 -
Biomolecules Jun 2024Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the...
Resveratrol, a phenylpropanoid compound, exhibits diverse pharmacological properties, making it a valuable candidate for health and disease management. However, the demand for resveratrol exceeds the capacity of plant extraction methods, necessitating alternative production strategies. Microbial synthesis offers several advantages over plant-based approaches and presents a promising alternative. stands out among microbial hosts due to its safe nature, abundant acetyl-CoA and malonyl-CoA availability, and robust pentose phosphate pathway. This study aimed to engineer for resveratrol production. The resveratrol biosynthetic pathway was integrated into by adding genes encoding tyrosine ammonia lyase from , 4-coumarate CoA ligase from , and stilbene synthase from . This resulted in the production of 14.3 mg/L resveratrol. A combination of endogenous and exogenous malonyl-CoA biosynthetic modules was introduced to enhance malonyl-CoA availability. This included genes encoding acetyl-CoA carboxylase 2 from , malonyl-CoA synthase, and a malonate transporter protein from . These strategies increased resveratrol production to 51.8 mg/L. The further optimization of fermentation conditions and the utilization of sucrose as an effective carbon source in YP media enhanced the resveratrol concentration to 141 mg/L in flask fermentation. By combining these strategies, we achieved a titer of 400 mg/L resveratrol in a controlled fed-batch bioreactor. These findings demonstrate the efficacy of as a platform for the de novo production of resveratrol and highlight the importance of metabolic engineering, enhancing malonyl-CoA availability, and media optimization for improved resveratrol production.
Topics: Resveratrol; Yarrowia; Metabolic Engineering; Sucrose; Acyltransferases; Vitis; Coenzyme A Ligases; Malonyl Coenzyme A; Nicotiana; Rhodotorula; Fermentation; Arabidopsis; Ammonia-Lyases; Bacterial Proteins
PubMed: 38927115
DOI: 10.3390/biom14060712 -
Cryobiology Jun 2024Non-permeable disaccharides are widely used as cryoprotectant agents due to their low cytotoxicity, but their protective effect is insufficient when the disaccharides...
Non-permeable disaccharides are widely used as cryoprotectant agents due to their low cytotoxicity, but their protective effect is insufficient when the disaccharides are present only extracellularly. On the other hand, cryoprotectant agent (CPA)-free cryopreservation has been recently achieved by instantaneously inkjet-freezing cells as tiny droplets. However, CPA-free cryopreservation requires skilled handling operations due to instability of the vitreous water without the CPA. In this study, the effectiveness of separately adding two types of disaccharides in inkjet freezing of 3T3 cells was evaluated and the following results were obtained. First, trehalose showed the highest effect at 0.57 M, twice the plasma osmolarity, with a maximum cell viability of over 90% when freezing 70 pL droplets. However, higher concentrations of trehalose decreased cell viability due to damage caused by dehydration. Similarly, sucrose gave cell viability close to 90% at 0.57 M with 70 pL droplets, and higher concentrations decreased cell viability. Next, the relationship between minimum trehalose concentrations to prevent intracellular and extracellular ice crystal formation and droplet size was analyzed. The results indicated that trehalose of less than 0.57 M was able to inhibit intracellular ice crystal formation even in the largest droplet used in this study, 450 pL, while trehalose of nearly 0.57 M was required to inhibit extracellular ice crystal formation in the smallest droplet, 70 pL. In other words, the suppression of extracellular ice crystals by the addition of CPA was shown to be crucial in improving the viability of inkjet superflash freezing.
PubMed: 38925357
DOI: 10.1016/j.cryobiol.2024.104932 -
Medical Sciences (Basel, Switzerland) Jun 2024Insulin exerts a crucial impact on glucose control, cellular growing, function, and metabolism. It is partially modulated by nutrients, especially as a response to the... (Review)
Review
Could Insulin Be a Better Regulator of Appetite/Satiety Balance and Body Weight Maintenance in Response to Glucose Exposure Compared to Sucrose Substitutes? Unraveling Current Knowledge and Searching for More Appropriate Choices.
BACKGROUND
Insulin exerts a crucial impact on glucose control, cellular growing, function, and metabolism. It is partially modulated by nutrients, especially as a response to the intake of foods, including carbohydrates. Moreover, insulin can exert an anorexigenic effect when inserted into the hypothalamus of the brain, in which a complex network of an appetite/hunger control system occurs. The current literature review aims at thoroughly summarizing and scrutinizing whether insulin release in response to glucose exposure may be a better choice to control body weight gain and related diseases compared to the use of sucrose substitutes (SSs) in combination with a long-term, well-balanced diet.
METHODS
This is a comprehensive literature review, which was performed through searching in-depth for the most accurate scientific databases and applying effective and relevant keywords.
RESULTS
The insulin action can be inserted into the hypothalamic orexigenic/anorexigenic complex system, activating several anorexigenic peptides, increasing the hedonic aspect of food intake, and effectively controlling the human body weight. In contrast, SSs appear not to affect the orexigenic/anorexigenic complex system, resulting in more cases of uncontrolled body weight maintenance while also increasing the risk of developing related diseases.
CONCLUSIONS
Most evidence, mainly derived from in vitro and in vivo animal studies, has reinforced the insulin anorexigenic action in the hypothalamus of the brain. Simultaneously, most available clinical studies showed that SSs during a well-balanced diet either maintain or even increase body weight, which may indirectly be ascribed to the fact that they cannot cover the hedonic aspect of food intake. However, there is a strong demand for long-term longitudinal surveys to effectively specify the impact of SSs on human metabolic health.
Topics: Humans; Insulin; Glucose; Appetite; Animals; Body Weight Maintenance; Sucrose; Satiation
PubMed: 38921683
DOI: 10.3390/medsci12020029 -
Journal of Fungi (Basel, Switzerland) Jun 2024is a phytopathogenic fungus that causes anthracnose in common beans () and presents a great diversity of pathotypes with different levels of virulence against bean...
is a phytopathogenic fungus that causes anthracnose in common beans () and presents a great diversity of pathotypes with different levels of virulence against bean varieties worldwide. The purpose of this study was to establish whether pathotypic diversity is associated with differences in the mycelial growth and secretion of plant-cell-wall-degrading enzymes (PCWDEs). We evaluated growth, hemicellulase and cellulase activity, and PCWDE secretion in four pathotypes of in cultures with glucose, bean hypocotyls and green beans of , and water hyacinth (). The results showed differences in the mycelial growth, hemicellulolytic activity, and PCWDE secretion among the pathotypes. Glucose was not the preferred carbon source for the best mycelial growth in all pathotypes, each of which showed a unique PCWDE secretion profile, indicating different levels of carbon catabolite regulation (CCR). The pathotypes showed a high differential hemicellulolytic capacity to degrade host and water hyacinth tissues, suggesting CCR by pentoses and that there are differences in the absorption and metabolism of different monosaccharides and/or disaccharides. We propose that different levels of CCR could optimize growth in different host tissues and could allow for consortium behavior in interactions with bean crops.
PubMed: 38921392
DOI: 10.3390/jof10060406 -
Applied and Environmental Microbiology Jun 2024Heterotrophic marine bacteria utilize and recycle dissolved organic matter (DOM), impacting biogeochemical cycles. It is currently unclear to what extent distinct DOM...
UNLABELLED
Heterotrophic marine bacteria utilize and recycle dissolved organic matter (DOM), impacting biogeochemical cycles. It is currently unclear to what extent distinct DOM components can be used by different heterotrophic clades. Here, we ask how a natural microbial community from the Eastern Mediterranean Sea (EMS) responds to different molecular classes of DOM (peptides, amino acids, amino sugars, disaccharides, monosaccharides, and organic acids) comprising much of the biomass of living organisms. Bulk bacterial activity increased after 24 h for all treatments relative to the control, while glucose and ATP uptake decreased or remained unchanged. Moreover, while the per-cell uptake rate of glucose and ATP decreased, that of Leucin significantly increased for amino acids, reflecting their importance as common metabolic currencies in the marine environment. dominated the peptides treatment, while different strains became dominant in response to amino acids and amino sugars. grew well on organic acids, and on disaccharides. A comparison with a recent laboratory-based study reveals similar peptide preferences for , while , for example, grew well in the lab on many substrates but dominated in seawater samples only when disaccharides were added. We further demonstrate a potential correlation between the genetic capacity for degrading amino sugars and the dominance of specific clades in these treatments. These results highlight the diversity in DOM utilization among heterotrophic bacteria and complexities in the response of natural communities.
IMPORTANCE
A major goal of microbial ecology is to predict the dynamics of natural communities based on the identity of the organisms, their physiological traits, and their genomes. Our results show that several clades of heterotrophic bacteria each grow in response to one or more specific classes of organic matter. For some clades, but not others, growth in a complex community is similar to that of isolated strains in laboratory monoculture. Additionally, by measuring how the entire community responds to various classes of organic matter, we show that these results are ecologically relevant, and propose that some of these resources are utilized through common uptake pathways. Tracing the path between different resources to the specific microbes that utilize them, and identifying commonalities and differences between different natural communities and between them and lab cultures, is an important step toward understanding microbial community dynamics and predicting how communities will respond to perturbations.
PubMed: 38920365
DOI: 10.1128/aem.00256-24