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Physiology & Behavior Sep 2023Physical exercise training has been positioned as a behavioral strategy to prevent or alleviate obesity via promotion of energy expenditure as well as modulation of...
Physical exercise training has been positioned as a behavioral strategy to prevent or alleviate obesity via promotion of energy expenditure as well as modulation of energy intake resulting from changes in dietary preference. Brain adaptations underlying the latter process are incompletely understood. Voluntary wheel running (VWR) is a self-reinforcing rodent paradigm that mimics aspects of human physical exercise training. Behavioral and mechanistic insight from such fundamental studies can help optimize therapies that improve body weight and metabolic health based on physical exercise training in humans. To assess the effects of VWR on dietary self-selection, male Wistar rats were given access to a two-component "no-choice" control diet (CD; consisting of prefabricated nutritionally complete pellets and a bottle with tap water) or a four-component free-choice high-fat high-sucrose diet (fc-HFHSD; consisting of a container with prefabricated nutritionally complete pellets, a dish with beef tallow, a bottle with tap water, and a bottle with 30% sucrose solution). Metabolic parameters and baseline dietary self-selection behavior during sedentary (SED) housing were measured for 21 days, after which half of the animals were allowed to run on a vertical running wheel (VWR) for another 30 days. This resulted in four experimental groups (SED, SED, VWR, and VWR). Gene expression of opioid and dopamine neurotransmission components, which are associated with dietary self-selection, was assessed in the lateral hypothalamus (LH) and nucleus accumbens (NAc), two brain regions involved in reward-related behavior, following 51 and 30 days of diet consumption and VWR, respectively. Compared to CD controls, consumption of fc-HFHSD before and during VWR did not alter total running distances. VWR and fc-HFHSD had opposite effects on body weight gain and terminal fat mass. VWR transiently lowered caloric intake and increased and decreased terminal adrenal and thymus mass, respectively, independent of diet. VWR during fc-HFHSD consumption consistently increased CD self-selection, had an acute negative effect on fat self-selection, and a delayed negative effect on sucrose solution self-selection compared to SED controls. Gene expression of opioid and dopamine neurotransmission components in LH and NAc were unaltered by fc-HFHSD or VWR. We conclude that VWR modulates fc-HFHSD component self-selection in a time-dependent manner in male Wistar rats.
Topics: Rats; Animals; Cattle; Male; Humans; Rats, Wistar; Motor Activity; Analgesics, Opioid; Dopamine; Diet, High-Fat; Body Weight; Sucrose
PubMed: 37196819
DOI: 10.1016/j.physbeh.2023.114239 -
Aryl-functionalised α,α'-Trehalose 6,6'-Glycolipid Induces Mincle-independent Pyroptotic Cell Death.Inflammation Aug 2023α,α'-Trehalose 6,6'-glycolipids have long been known for their immunostimulatory properties. The adjuvanticity of α,α'-trehalose 6,6'-glycolipids is mediated by...
α,α'-Trehalose 6,6'-glycolipids have long been known for their immunostimulatory properties. The adjuvanticity of α,α'-trehalose 6,6'-glycolipids is mediated by signalling through the macrophage inducible C-type lectin (Mincle) and the induction of an inflammatory response. Herein, we present an aryl-functionalised trehalose glycolipid, AF-2, that leads to the release of cytokines and chemokines, including IL-6, MIP-2 and TNF-α, in a Mincle-dependent manner. Furthermore, plate-coated AF-2 also leads to the Mincle-independent production of IL-1β, which is unprecedented for this class of glycolipid. Upon investigation into the mode of action of plate-coated AF-2, it was observed that the treatment of WT and Mincle bone marrow derived macrophages (BMDM), murine RAW264.7 cells, and human monocytes with AF-2 led to lytic cell death, as evidenced using Sytox Green and lactate dehydrogenase assays, and confocal and scanning electron microscopy. The requirement for functional Gasdermin D and Caspase-1 for IL-1β production and cell death by AF-2 confirmed pyroptosis as the mode of action of AF-2. The inhibition of NLRP3 and K efflux reduced AF-2 mediated IL-1β production and cell death, and allowed us to conclude that AF-2 leads to Capase-1 dependent NLRP3 inflammasome-mediated cell death. The unique mode of action of plate-coated AF-2 was surprising and highlights how the physical presentation of Mincle ligands can lead to dramatically different immunological outcomes.
Topics: Mice; Animals; Humans; Glycolipids; Pyroptosis; Trehalose; NLR Family, Pyrin Domain-Containing 3 Protein; Furylfuramide; Lectins, C-Type
PubMed: 37140682
DOI: 10.1007/s10753-023-01814-5 -
Frontiers in Endocrinology 2024A high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or...
INTRODUCTION
A high-fat/high-sucrose diet leads to adverse metabolic changes that affect insulin sensitivity, function, and secretion. The source of fat in the diet might inhibit or increase this adverse effect. Fish oil and cocoa butter are a significant part of our diets. Yet comparisons of these commonly used fat sources with high sucrose on pancreas morphology and function are not made. This study investigated the comparative effects of a fish oil-based high-fat/high-sucrose diet (Fish-HFDS) versus a cocoa butter-based high-fat/high-sucrose diet (Cocoa-HFDS) on endocrine pancreas morphology and function in mice.
METHODS
C57BL/6 male mice (n=12) were randomly assigned to dietary intervention either Fish-HFDS (n=6) or Cocoa-HFDS (n=6) for 22 weeks. Intraperitoneal glucose and insulin tolerance tests (IP-GTT and IP-ITT) were performed after 20-21 weeks of dietary intervention. Plasma concentrations of c-peptide, insulin, glucagon, GLP-1, and leptin were measured by Milliplex kit. Pancreatic tissues were collected for immunohistochemistry to measure islet number and composition. Tissues were multi-labelled with antibodies against insulin and glucagon, also including expression on Pdx1-positive cells.
RESULTS AND DISCUSSION
Fish-HFDS-fed mice showed significantly reduced food intake and body weight gain compared to Cocoa-HFDS-fed mice. Fish-HFDS group had lower fasting blood glucose concentration and area under the curve (AUC) for both GTT and ITT. Plasma c-peptide, insulin, glucagon, and GLP-1 concentrations were increased in the Fish-HFDS group. Interestingly, mice fed the Fish-HFDS diet displayed higher plasma leptin concentration. Histochemical analysis revealed a significant increase in endocrine pancreas β-cells and islet numbers in mice fed Fish-HFDS compared to the Cocoa-HFDS group. Taken together, these findings suggest that in a high-fat/high-sucrose dietary setting, the source of the fat, especially fish oil, can ameliorate the effect of sucrose on glucose homeostasis and endocrine pancreas morphology and function.
Topics: Male; Mice; Animals; Leptin; Glucagon; Sucrose; Fish Oils; C-Peptide; Mice, Inbred C57BL; Islets of Langerhans; Insulin; Glucose; Glucagon-Like Peptide 1; Dietary Fats
PubMed: 38414818
DOI: 10.3389/fendo.2024.1265799 -
BMC Microbiology Aug 2023The ascomycetous heterothallic yeast Wickerhamomyces anomalus (WA) has received considerable attention and has been widely reported in the winemaking industry for its...
BACKGROUND
The ascomycetous heterothallic yeast Wickerhamomyces anomalus (WA) has received considerable attention and has been widely reported in the winemaking industry for its distinctive physiological traits and metabolic attributes. An increased concentration of ethanol during ethanol fermentation, however, causes ethanol stress (ES) on the yeast cells. Trehalose has been implicated in improving survival under various stress conditions in microorganisms. Herein, we determined the effects of trehalose supplementation on the survival, differentially expressed genes (DEGs), cellular morphology, and oxidative stress tolerance of WA in response to ES.
RESULTS
The results indicated that trehalose improved the survival and anomalous surface and ultrastructural morphology of WA. Additionally, trehalose improved redox homeostasis by reducing the levels of reactive oxygen species (ROS) and inducing the activities of antioxidant enzymes. In addition, DEGs affected by the application of trehalose were enriched in these categories including in gene expression, protein synthesis, energy metabolism, and cell cycle pathways. Additionally, trehalose increased the content of intracellular malondialdehyde (MDA) and adenosine triphosphate.
CONCLUSIONS
These results reveal the protective role of trehalose in ES mitigation and strengthen the possible uses of WA in the wine fermentation sector.
Topics: Trehalose; Saccharomycetales; Adenosine Triphosphate; Ethanol
PubMed: 37644381
DOI: 10.1186/s12866-023-02982-y -
EBioMedicine Apr 2024Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about... (Randomized Controlled Trial)
Randomized Controlled Trial
Acute and two-week effects of neotame, stevia rebaudioside M and sucrose-sweetened biscuits on postprandial appetite and endocrine response in adults with overweight/obesity-a randomised crossover trial from the SWEET consortium.
BACKGROUND
Sweeteners and sweetness enhancers (S&SE) are used to replace energy yielding sugars and maintain sweet taste in a wide range of products, but controversy exists about their effects on appetite and endocrine responses in reduced or no added sugar solid foods. The aim of the current study was to evaluate the acute (1 day) and repeated (two-week daily) ingestive effects of 2 S&SE vs. sucrose formulations of biscuit with fruit filling on appetite and endocrine responses in adults with overweight and obesity.
METHODS
In a randomised crossover trial, 53 healthy adults (33 female, 20 male) with overweight/obesity in England and France consumed biscuits with fruit filling containing 1) sucrose, or reformulated with either 2) Stevia Rebaudioside M (StRebM) or 3) Neotame daily during three, two-week intervention periods with a two-week washout. The primary outcome was composite appetite score defined as [desire to eat + hunger + (100 - fullness) + prospective consumption]/4.
FINDINGS
Each formulation elicited a similar reduction in appetite sensations (3-h postprandial net iAUC). Postprandial insulin (2-h iAUC) was lower after Neotame (95% CI (0.093, 0.166); p < 0.001; d = -0.71) and StRebM (95% CI (0.133, 0.205); p < 0.001; d = -1.01) compared to sucrose, and glucose was lower after StRebM (95% CI (0.023, 0.171); p < 0.05; d = -0.39) but not after Neotame (95% CI (-0.007, 0.145); p = 0.074; d = -0.25) compared to sucrose. There were no differences between S&SE or sucrose formulations on ghrelin, glucagon-like peptide 1 or pancreatic polypeptide iAUCs. No clinically meaningful differences between acute vs. two-weeks of daily consumption were found.
INTERPRETATION
In conclusion, biscuits reformulated to replace sugar using StRebM or Neotame showed no differences in appetite or endocrine responses, acutely or after a two-week exposure, but can reduce postprandial insulin and glucose response in adults with overweight or obesity.
FUNDING
The present study was funded by the Horizon 2020 program: Sweeteners and sweetness enhancers: Impact on health, obesity, safety and sustainability (acronym: SWEET, grant no: 774293).
Topics: Adult; Male; Humans; Female; Appetite; Sucrose; Overweight; Stevia; Taste; Cross-Over Studies; Prospective Studies; Blood Glucose; Obesity; Sweetening Agents; Glucose; Insulin; Sugars; Dipeptides; Trisaccharides; Diterpenes, Kaurane
PubMed: 38553262
DOI: 10.1016/j.ebiom.2024.105005 -
Journal of Dairy Science Dec 2023β-galactosidase (enzymatic class 3.2.1.23) is one of the dairy industry's most important and widely used enzymes. The enzyme is part of a large family known to catalyze... (Review)
Review
β-galactosidase (enzymatic class 3.2.1.23) is one of the dairy industry's most important and widely used enzymes. The enzyme is part of a large family known to catalyze hydrolysis and transglycosylation reactions. Its hydrolytic activity is commonly used to decrease lactose content in dairy products, while its transglycosylase activity has recently been used to synthesize galacto-oligosaccharides (GOS). During the past couple of years, researchers have focused on studying β-galactosidase isolated and purified from lactic acid bacteria. This review will focus on β-galactosidase purified and characterized from what used to be the Lactobacillus genera. Furthermore, particular emphasis is given to its kinetics, biochemical characteristics, GOS production, market, and utilization by Lactobacilllaceae species.
Topics: Animals; Lactobacillaceae; Oligosaccharides; Lactose; Catalysis; beta-Galactosidase; Galactose
PubMed: 37678769
DOI: 10.3168/jds.2023-23392 -
PloS One 2023Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol...
Lysosomes play important roles in catabolism, nutrient sensing, metabolic signaling, and homeostasis. NPC1 deficiency disrupts lysosomal function by inducing cholesterol accumulation that leads to early neurodegeneration in Niemann-Pick type C (NPC) disease. Mitochondria pathology and deficits in NPC1 deficient cells are associated with impaired lysosomal proteolysis and metabolic signaling. It is thought that activation of the transcription factor TFEB, an inducer of lysosome biogenesis, restores lysosomal-autophagy activity in lysosomal storage disorders. Here, we investigated the effect of trehalose, a TFEB activator, in the mitochondria pathology of NPC1 mutant fibroblasts in vitro and in mouse developmental Purkinje cells ex vivo. We found that in NPC1 mutant fibroblasts, serum starvation or/and trehalose treatment, both activators of TFEB, reversed mitochondria fragmentation to a more tubular mitochondrion. Trehalose treatment also decreased the accumulation of Filipin+ cholesterol in NPC1 mutant fibroblasts. However, trehalose treatment in cerebellar organotypic slices (COSCs) from wild-type and Npc1nmf164 mice caused mitochondria fragmentation and lack of dendritic growth and degeneration in developmental Purkinje cells. Our data suggest, that although trehalose successfully restores mitochondria length and decreases cholesterol accumulation in NPC1 mutant fibroblasts, in COSCs, Purkinje cells mitochondria and dendritic growth are negatively affected possibly through the overactivation of the TFEB-lysosomal-autophagy pathway.
Topics: Animals; Humans; Mice; Cholesterol; Fibroblasts; Intracellular Signaling Peptides and Proteins; Lysosomes; Mitochondria; Niemann-Pick C1 Protein; Niemann-Pick Disease, Type C; Purkinje Cells; Trehalose
PubMed: 38033125
DOI: 10.1371/journal.pone.0294312 -
Bioengineered Dec 2023The versatility of a well-known fibrous crop, (kenaf) is still relatively new to many. Kenaf's potential applications, which can be extended even into critical...
The versatility of a well-known fibrous crop, (kenaf) is still relatively new to many. Kenaf's potential applications, which can be extended even into critical industries such as pharmaceutical and food industries, have always been overshadowed by its traditionally grown fiber. Therefore, this study aimed to venture into the biotechnological approach in reaping the benefits of kenaf through plant cell suspension culture to maximize the production of kenaf callus biomass (KCB) and exopolysaccharide (EPS), which is deemed to be more sustainable. A growth curve was established which indicates that cultivating kenaf callus in suspension culture for 22 days gives the highest KCB (9.09 ± 1.2 g/L) and EPS (1.1 ± 0.02 g/L). Using response surface methodology (RSM), it was found that sucrose concentration, agitation speed, and naphthalene acetic acid (NAA) concentration can affect the production of KCB and EPS significantly ( < 0.05) while 2,4-dichlorophenoxy acetic acid (2,4-D) was deemed insignificant. To maximize the final yield of KCB and EPS, the final optimized variables are 50 g/L sucrose, 147.02 rpm, and 2 mg/L of NAA. To conclude, the optimized parameters for the cell suspension culture of kenaf callus serve as the blueprint for any sustainable large-scale production in the future and provide an alternative cultivating method to kenaf traditional farming.
Topics: Hibiscus; Biomass; Cell Culture Techniques; Sucrose; Acetates
PubMed: 37791464
DOI: 10.1080/21655979.2023.2262203 -
Scientific Reports Sep 2023The development of an efficient, safe, and environment-friendly technique to terminate tuber dormancy in potatoes (Solanum tuberosum L.) is of great concern due to the...
The development of an efficient, safe, and environment-friendly technique to terminate tuber dormancy in potatoes (Solanum tuberosum L.) is of great concern due to the immense scope of multiple cropping all over the globe. The breakage of tuber dormancy has been associated with numerous physiological changes, including a decline in the level of starch and an increase in the levels of sugars during storage of freshly harvested seed potatoes, although their consistency across genotypes and various dormancy-breaking techniques have not yet been fully elucidated. The purpose of the present research is to assess the efficacy of four different dormancy-breaking techniques, such as soaking in 90, 60, or 30 mg L solutions of benzyl amino purine (BAP) and 30, 20, or 10 mg L gibberellic acid (GA3) alone and in the combination of optimized concentrations; cold pre-treatment at 6, 4, or 2 °C; electric shock at 80, 60, 40, or 20 Vs; and irradiation at 3.5, 3, 2.5, 2, 1.5, or 1 kGy on the tuber dormancy period and sprout length of six genotypes. Furthermore, the changes that occurred in tuber weight and endogenous starch, sucrose, fructose, and glucose contents in experimental genotypes following the application of these techniques were also examined. Overall, the most effective technique to terminate tuber dormancy and hasten spout growth was the combined application of BAP and GA, which reduced the length of dormancy by 9.6 days compared to the untreated control, following 6.7 days of electric current, 4.4 days of cold pre-treatment, and finally irradiation (3.3 days). The 60 mg L solution of BAP greatly reduced the dormancy period in all genotypes but did not affect the sprout length at all. The genotypes showed a weak negative correlation (r = - 0.4) (P < 0.05) of endogenous starch contents with dormancy breakage and weight loss or a moderate (r = - 0.5) correlation with sprout length, but a strong positive correlation (r = 0.8) of tuber glucose, fructose, and sucrose contents with dormancy breakage and weight loss. During 3 weeks of storage, sprouting commencement and significant weight loss occurred as tuber dormancy advanced towards breakage due to a reduction in starch and an increase in the sucrose, fructose, and glucose contents of the tubers. These findings could be advantageous for postponing or accelerating seed potato storage as well as investigating related physiological research in the future.
Topics: Sugars; Solanum tuberosum; Glucose; Death; Fructose; Genotype; Starch; Sucrose
PubMed: 37684294
DOI: 10.1038/s41598-023-37711-y -
Translational Psychiatry Jan 2024Impaired motivational drive is a key feature of depression. Chronic stress is a known antecedent to the development of depression in humans and depressive-like states in...
Impaired motivational drive is a key feature of depression. Chronic stress is a known antecedent to the development of depression in humans and depressive-like states in animals. Whilst there is a clear relationship between stress and motivational drive, the mechanisms underpinning this association remain unclear. One hypothesis is that the endocrine system, via corticotropin-releasing hormone (CRH) in the paraventricular nucleus of the hypothalamus (PVN; PVN), initiates a hormonal cascade resulting in glucocorticoid release, and that excessive glucocorticoids change brain circuit function to produce depression-related symptoms. Another mostly unexplored hypothesis is that the direct activity of PVN neurons and their input to other stress- and reward-related brain regions drives these behaviors. To further understand the direct involvement of PVN neurons in motivation, we used optogenetic stimulation to activate these neurons 1 h/day for 5 consecutive days and showed increased acute stress-related behaviors and long-lasting deficits in the motivational drive for sucrose. This was associated with increased Fos-protein expression in the lateral hypothalamus (LH). Direct stimulation of the PVN inputs in the LH produced a similar pattern of effects on sucrose motivation. Together, these data suggest that PVN neuronal activity may be directly responsible for changes in motivational drive and that these behavioral changes may, in part, be driven by PVN synaptic projections to the LH.
Topics: Animals; Humans; Corticotropin-Releasing Hormone; Adrenocorticotropic Hormone; Motivation; Pituitary Hormone-Releasing Hormones; Optogenetics; Hypothalamus; Glucocorticoids; Neurons; Sucrose
PubMed: 38191479
DOI: 10.1038/s41398-023-02710-0