Sucrose Intake Research Articles

Excessive sucrose exacerbates high fat diet-induced hepatic inflammation and fibrosis promoting osteoarthritis in mice model

Osteoarthritis (OA) is marked by chronic low-grade systemic inflammation and cartilage destruction. High fat diet causes obesity and increases the risk of knee OA-development. However, the impact of high dietary sugar intake on OA pathogenesis has not been elucidated yet. Therefore, we investigated the effects of a high-fat and high-sucrose (HF+HS) diet in experimental OA mouse models. Eight-week-old male C57BL/6J mice were fed a standard chow (n=6), high-fat (HF) (n=5), or HF+HS (n=7) diets for 12 weeks; thereafter, the mice underwent surgical destabilization of the medial meniscus (DMM) and received the same experimental diets for an additional 8 weeks. The pathogenesis of knee OA, obesogenic parameters, and inflammation levels in the liver and adipose tissue were investigated. HF+HS diet induced severe cartilage erosion with osteophyte development and subchondral bone plate thickening, indicating that HF+HS diet exacerbated OA. Despite marginal differences in metabolic parameters, hepatic free cholesterol accumulation increased in mice with DMM-induced OA fed on HF+HS diet than in those fed HF diet. Notably, the levels of inflammatory cytokines and fibrosis markers were greater in the livers of mice with DMM-induced OA, fed on HF+HS diet than those in the control group. However, adipose tissue remodeling was not affected by the HF+HS diet. These findings indicate that excess sucrose intake along with a HF diet triggers hepatic inflammation and fibrosis, thereby, contributing to OA pathogenesis.

Sucrose Consumption during Late Adolescence Impairs Adult Neurogenesis of the Ventral Dentate Gyrus without Inducing an Anxiety-like Behavior.

Sucrose consumption impairs behavioral and cognitive functions that correlate with decreased neurogenesis in animal models. When consumed during early adolescence, this disaccharide promotes anxious and depressive behaviors, along with a reduction in the generation of new neurons in the dentate gyrus of the hippocampus. Data concerning sucrose consumption during late adolescence are lacking, and the effect of sucrose intake on the ventral dentate gyrus of the hippocampus (which modulates anxiety and depression) remains elusive. Here, we tested whether sucrose intake during late adolescence causes anxiety or impaired neurogenesis in the ventral dentate gyrus. Rats did not display anxiety-like behaviors neither at the light-dark box test nor at the open field exploration. However, there was a significant increase in proliferative cells in the subgranular zone of the ventral dentate gyrus in rats exposed to sucrose (p < 0.05). This increased proliferation corresponded to neural stem cells (Radial Type 1 cells) in the group exposed to sucrose until adulthood but was not present in rats exposed to sucrose only during late adolescence. Remarkably, the phosphorylation of ERK1/2 kinases was increased in the hippocampi of rats exposed to sucrose only during late adolescence, suggesting that the increased proliferation in this group could be mediated by the MAPK pathway. On the other hand, although no differences were found in the number of immature granular neurons, we observed more immature granular neurons with impaired dendritic orientation in both groups exposed to sucrose. Finally, GAD65/67 and BCL2 levels did not change between groups, suggesting an unaltered hippocampal GABAergic system and similar apoptosis, respectively. This information provides the first piece of evidence of how sucrose intake, starting in late adolescence, impacts ventral dentate gyrus neurogenesis and contributes to a better understanding of the effects of this carbohydrate on the brain at postnatal stages.

ODP321 Impact of a Maternal High-Sucrose Diet in Rats on Fetal Physiology and the Placenta

Abstract Consumption of sucrose (table sugar) is high in much of the world. The effects of maternal sucrose intake on the placenta and fetal brain remain unknown. In rats, maternal consumption of sucrose at a human-relevant level alters the mother's physiology and steroids, as well as the adult offspring's brain and behavior. Effects in mothers are impaired glucose tolerance, increased liver lipids, increased adipose inflammation, and decreased corticosterone levels in the blood but not in the brain. In contrast, in adult female offspring, maternal sucrose intake increases corticosterone levels in the blood and the brain. In adult male offspring, maternal sucrose intake increases preference for high-sucrose and high-fat diets as well as motivation for sugar rewards in a progressive ratio task. In this study, we investigate the underlying mechanisms of the observed behavioral and endocrine effects in the adult offspring. We examine anti-inflammatory steroids, steroidogenic enzymes and cytokines in the placenta, amniotic fluid, fetal blood and brain. In our model, we feed rat dams either a high-sucrose diet (26% of kCal) or an isocaloric, matched, control diet (1% sucrose) 10 weeks prior to and during gestation. At embryonic day 19 (E19), we collected maternal serum, placenta, amniotic fluid, fetal blood, and fetal brain. We used Palkovits punch to microdissect the placenta and fetal brain. Next, we used liquid chromatography-tandem mass spectrometry (LC-MS/MS), which is highly sensitive and specific, to measure multiple steroids (e. g. corticosterone, estrone, allopregnanolone). We examined multiple regions of the fetal brain (e. g. prefrontal cortex, nucleus accumbens, hypothalamus, hippocampus). We will also examine neuronal proliferation, microglia and tyrosine hydroxylase immunoreactivity in the fetal brain. Maternal high-sucrose diet increased 11-dehydrocorticosterone (inactive metabolite of corticosterone) and aldosterone in maternal serum and amniotic fluid. Testosterone and androstenedione were significantly higher in the amniotic fluid of male fetuses than female fetuses. Placental steroidogenic enzymes 3β-HSD and CYP19 were not affected by maternal diet or fetal sex; however, 3β-HSD activity was higher in the decidua than in the fetal part of the placenta. Steroid and cytokine data from the placenta, fetal blood and fetal brain are currently being analyzed. Ongoing analyses examine how a maternal high-sucrose diet affects brain development possibly by increasing inflammation. Presentation: No date and time listed

18β-Glycyrrhetinic Acid Ameliorates Neuroinflammation Linked Depressive Behavior Instigated by Chronic Unpredictable Mild Stress via Triggering BDNF/TrkB Signaling Pathway in Rats.

Evidence shows that inflammatory responses may encompass the onset of severe depressive illness. Traditionally used licorice contains 18β-glycyrrhetinic acid (18βGA), which has been demonstrated to reduce inflammation and oxidative stress. This study investigates the antidepressant effects of 18βGA and the underlying mechanism in rats exposed to chronic unpredictable mild stress (CUMS). Wistar rats were exposed to CUMS for 36 consecutive days to establish depression. 18βGA (10, 20, and 50mg/kg) or fluoxetine was given once daily (from day 30 to day 36). Thereafter, behavior parameters (sucrose preference test, forced-swimming test, open-field test, body weight), pro-inflammatory cytokines, neurotransmitters, adrenocorticotropic hormone (ACTH), corticosterone (CORT), and liver biomarkers were studied. Immunohistochemistry and western blot analyses were conducted to investigate the protein's expression. 18βGA (20 and 50mg/kg) treatment increased sucrose intake, locomotion in the open-field test, decreased immobility time in the forced swim test, and improved body weight in CUMS-exposed rats. The therapy of 18βGAdramatically declined cytokines, ACTH and CORT and improved 5HT and norepinephrine in CUMS rats. Furthermore, BDNF and TrkB proteins were down-regulated in CUMS group, which was increased to varying degrees by 18βGA at doses of 20 and 50mg/kg. Therefore, 18βGA ameliorates depressive-like behavior persuaded by chronic unpredictable mild stress, decreases neuroinflammation, liver biomarkers, stress hormones, and improves body weight, brain neurotransmitter concentration via activating on BDNF/TrkB signaling pathway in both PFC and hippocampus in rats.

The effects of sugar in drinking water on Streptococcus pyogenes colonisation in a murine nasopharyngeal infection model

The number of sugar-sweetened beverages consumed per day has been associated with an increased risk of acute rheumatic fever, an autoimmune disease triggered by superficial Streptococcus pyogenes infection. To explore if there could be a biological basis for this association, we used a mouse model of S. pyogenes nasopharyngeal colonisation combined with a dietary intervention. We observed an increased bacterial load in the nasopharynx of mice receiving sucrose drinking water post-infection, suggesting that high sucrose intake promotes S. pyogenes growth and/or survival. This provides new insight into the potential biological basis behind the association seen in humans.

Delayed feeding of a high-sucrose diet led to increased body weight by affecting the circadian rhythm of body temperature and hepatic lipid-metabolism genes in rats

Skipping breakfast is an irregular feeding behavior, typically in young people. In our previous study, we established a 4 h-delayed feeding protocol for rats as a breakfast-skipping model and showed that the 4 h-delayed feeding of a high-fat diet led to body weight gain in rats. Excess sucrose induces metabolic syndrome and fatty liver. Recently, excess sucrose intake has received increased attention. Young people generally consume more sugar than adults do. In the present study, we investigated whether a 4 h-delayed feeding promoted high-sucrose diet-induced abnormalities in lipid metabolism, such as fatty liver and obesity in rats. The 4 h-delayed feeding rats showed increased body weight gain, although it did not induce fatty liver and hyperlipidemia compared to normal feeding rats. Serum insulin concentration during the feeding period was higher than in the control rats, suggesting that slight insulin resistance was induced by the 4 h-delayed feeding. The surge in body temperature was also delayed by 4 h in response to the 4 h-delayed feeding. This delay would result in less energy expenditure to increase body weight. The oscillations of hepatic lipid and glucose metabolism-related gene expression were delayed by almost 2–4 h, and the clock genes were delayed by approximately 2 h. The 4 h-delayed feeding induced weight gain by affecting body temperature, insulin resistance, and circadian oscillation of lipid metabolism-related genes in rats fed a high-sucrose diet, suggesting that a high sucrose intake with breakfast skipping leads to obesity.

Oral Supplementation with the Polyamine Spermidine Affects Hepatic but Not Pulmonary Lipid Metabolism in Lean but Not Obese Mice.

The polyamine spermidine is discussed as a caloric restriction mimetic and therapeutic option for obesity and related comorbidities. This study tested oral spermidine supplementation with regard to the systemic, hepatic and pulmonary lipid metabolism under different diet conditions. Male C57BL/6 mice were fed a purified control (CD), high sucrose (HSD) or high fat (HFD) diet with (-S) or without spermidine for 30 weeks. In CD-fed mice, spermidine decreased body and adipose tissue weights and reduced hepatic lipid content. The HSD induced hepatic lipid synthesis and accumulation and hypercholesterolemia. This was not affected by spermidine supplementation, but body weight and blood glucose were lower in HSD-S compared to HSD. HFD-fed mice showed higher body and fat depot weights, prediabetes, hypercholesterolemia and severe liver steatosis, which were not altered by spermidine. Within the liver, spermidine diminished hepatic expression of lipogenic transcription factors SREBF1 and 2 under HSD and HFD and affected the expression of other lipid-related enzymes. In contrast, diet and spermidine exerted only minor effects on pulmonary parameters. Thus, oral spermidine supplementation affects lipid metabolism in a diet-dependent manner, with significant reductions in body fat and weight under physiological nutrition and positive effects on weight and blood glucose under high sucrose intake, but no impact on dietary fat-related parameters.

Chronic intake of high dietary sucrose induces sexually dimorphic metabolic adaptations in mouse liver and adipose tissue

Almost all effective treatments for non-alcoholic fatty liver disease (NAFLD) involve reduction of adiposity, which suggests the metabolic axis between liver and adipose tissue is essential to NAFLD development. Since excessive dietary sugar intake may be an initiating factor for NAFLD, we have characterized the metabolic effects of liquid sucrose intake at concentrations relevant to typical human consumption in mice. We report that sucrose intake induces sexually dimorphic effects in liver, adipose tissue, and the microbiome; differences concordant with steatosis severity. We show that when steatosis is decoupled from impairments in insulin responsiveness, sex is a moderating factor that influences sucrose-driven lipid storage and the contribution of de novo fatty acid synthesis to the overall hepatic triglyceride pool. Our findings provide physiologic insight into how sex influences the regulation of adipose-liver crosstalk and highlight the importance of extrahepatic metabolism in the pathogenesis of diet-induced steatosis and NAFLD.

Fibroblast growth factor 21 and dietary macronutrient intake in female mice

Fibroblast growth factor- 21 (FGF21) is a metabolic stress hormone that is released from the liver in response to various nutritional challenges. Because of its notable effects to improve metabolic health, including body fat loss, glucose control, and hepatosteatosis, several pharmaceutical analogs of FGF21 are in development for the treatment of metabolic disease. In addition, a small but developing literature clearly demonstrates that FGF21 also controls feeding behavior. Pharmacological administration of FGF21 reduces the consumption of simple sugars and other sweet tastants, and it increases the consumption of dietary proteins in males, suggesting another potential mechanism by which FGF21-treatment could improve metabolic health— by promoting healthy eating. Despite that sex is a key biological variable influencing feeding behavior and macronutrient selection, the current literature to date primarily on males. In this study, we investigated the effect of FGF21 on sucrose intake and macronutrient selection in female mice. Similar to our previous findings in male mice, we report that FGF21 administration decreases the consumption of sucrose solution by females, and that this is offset by increased chow intake. Also in agreement with our previous findings in males, we report that FGF21 increases the consumption of dietary protein by female mice, and this is offset by either reduced carbohydrate or by reduced fat intake. Lastly, we find that the effect of FGF21 to direct macronutrient intake in females depends on its actions in neurons. Overall, our data support a role for FGF21 to direct macronutrient intake in a similar manner in female and male mice.

Paeoniflorin Ameliorates Colonic Fibrosis in Rats with Postinfectious Irritable Bowel Syndrome by Inhibiting the Leptin/LepRb Pathway.

Postinfectious irritable bowel syndrome (PI-IBS) is a highly prevalent gastrointestinal disorder associated with immune dysregulation and depression- and anxiety-like behaviors. Through traditional medicine, the active ingredient of Paeoniae Radix called paeoniflorin (PF) was previously found to prevent the symptoms of PI-IBS. However, there is limited information on the effects of PF on intestinal function and depression- and anxiety-like symptoms in PI-IBS animal models. Here, we aimed to determine the effects of PF treatment on the symptoms of PI-IBS in a rat model. The PI-IBS rat model was established via early postnatal sibling deprivation (EPSD), trinitrobenzenesulfonic acid (TNBS), and chronic unpredictable mild stress (CUMS) stimulation and then treated with different dosages of PF (10, 20, and 40 mg/kg) and leptin (1 and 10 mg/kg). The fecal water content and body weight were measured to evaluate the intestinal function, while the two-bottle test for sucrose intake, open field test (OFT), and elevated plus maze test (EMT) were performed to assess behavioral changes. The serum leptin levels were also measured using an enzyme-linked immunosorbent assay. Furthermore, the expressions of leptin and its receptor, LepRb, were detected in colonic mucosal tissues through an immunohistochemical assay. The activation of the PI3K/AKT signaling pathway and the expression of brain-derived neurotrophic factor (BDNF) were also detected via western blotting. After the experimental period, the PI-IBS rats presented decreased body weight and increased fecal water content, which coincided with elevated leptin levels and heightened depression- and anxiety-like behaviors (e.g., low sucrose intake, less frequency in the center areas during OFT, and fewer activities in the open arms during EMT). However, the PF treatment ameliorated these observed symptoms. Furthermore, PF not only inhibited leptin/LepRb expression but also reduced the PI3K/AKT phosphorylation and BDNF expression in PI-IBS rats. Notably, cotreatment with leptin (10 mg/kg) reduced the effects of PF (20 mg/kg) on colonic fibrosis, leptin/LepRb expression, and PI3K/AKT activation. Therefore, our findings suggest that leptin is targeted by PF via the leptin/LepRb pathway, consequently ameliorating the symptoms of PI-IBS. Our study also contributes novel insights for elucidating the pharmacological action of PF on gastrointestinal disorders and may be used for the clinical treatment of PI-IBS in the future.

The Influence of Unlimited Sucrose Intake on Body Weight and Behavior-Findings from a Mouse Model.

A potential relationship between unrestricted sucrose intake (USI), overweight, and emotional/behavioral control has not been well documented. We examined the influence of USI and having less sweetness than expected on body weight (BW), motor/exploratory, anxiety-like, and social dominant behavior in adult C57BL/6J male mice. Animals had free access to water (group 1) or 32% sucrose and water (sucrose groups 2–5) for 10 days. Then, group 2 remained with 32% sucrose while groups 3–5 were subjected to the downshift (24 h access to 4%, 8%, or 16% sucrose). All experimental groups were weighed and tested in the novel-open arena (NA), elevated plus maze (EPM), and tube tests to assess BW, motor/exploratory, anxiety-like, and social dominance behavior, respectively. USI did not influence animals’ BW but produced hyperactivity and anxiolytic-like behavior, which was evident in EPM but not in NA; the outcomes of the downshift were comparable. USI did not influence successes/wins in the tube test but altered emotions that drive the winning, favoring a less anxious behavioral phenotype; this was not evident in the downshifted groups. Observed findings suggest that USI promotes sensation-seeking and motivates dominance, without changing BW, while blunted emotional base of social dominance might be an early mark of the downshift.

Effects of Chronic Mild Stress on Cardiac Autonomic Activity, Cardiac Structure and Renin-Angiotensin-Aldosterone System in Male Rats.

Simple SummaryStress can cause heart disease by changing cardiac structure and/or function as assessed by heart rate variability; however, this may or may not happen when exposed to daily stress. Therefore, this study was conducted to investigate alterations in cardiac structure and cardiac control through autonomic activity, and in the renin–angiotensin–aldosterone system in male rats after exposure to 4-week chronic mild stress as an animal model for daily stress exposure in humans. The results showed that chronic mild stress increased both sympathetic and parasympathetic autonomic activities without affecting their balance. The renin–angiotensin–aldosterone system, which was partly responsible for changes in cardiac structure, was also affected. These data suggest that cardiac autonomic control and cardiac structure were affected by 4-week mild stress; however, this effect was probably in an adaptable period as the sympathetic and parasympathetic activities were in balance.Stress is associated with cardiovascular disease. One accepted mechanism is autonomic imbalance. In this study, we investigated the effects of chronic mild stress (CMS) on cardiac autonomic control, cardiac structure and renin–angiotensin–aldosterone system (RAAS) activity in adult male Sprague Dawley rats. The CMS model provides a more realistic simulation of daily stress. The animals were divided into control and CMS, and were exposed to 4-week mild stressors. The electrocardiogram recording, sucrose intake and parameters related to stress, cardiac alterations and RAAS were determined. The results showed that CMS had lower body weight and higher sucrose intake. The heart rate variability (HRV) revealed that CMS increased autonomic activity without affecting its balance. The increased RAAS activity with upregulated angiotensin type 1 receptor mRNA expression was shown in CMS. The increased sympathetic activity or RAAS was correlated with stress. Moreover, the altered cardiac structure (i.e., heart weight and cardiomyocyte cross-sectional area) were correlated with stress-, sympathetic- and RAAS-related parameters. These indicated that CMS-induced cardiac hypertrophy was the result of both sympathetic and RAAS activation. Therefore, it could be concluded that 4-week CMS in male rats induced negative emotion as shown by increased sucrose intake, and increased cardiac autonomic and RAAS activities, which may be responsible for mild cardiac hypertrophy. The cardiac hypertrophy herein was possibly in an adaptive, not pathological, stage, and the cardiac autonomic function was preserved as the autonomic activities were in balance.

Ca:Mg ratio, medium-chain fatty acids, and the gut microbiome

Ketogenic medium-chain fatty acids (MCFAs) with profound health benefits are commonly found in dairy products, palm kernel oil and coconut oil. We hypothesize that magnesium (Mg) supplementation leads to enhanced gut microbial production of MCFAs and, in turn, increased circulating MCFAs levels. We tested this hypothesis in the Personalized Prevention of Colorectal Cancer Trial (PPCCT) (NCT01105169), a double-blind 2×2 factorial randomized controlled trial enrolling 240 participants. Six 24-hdietary recalls were performed for all participants at the baseline and during the intervention period. Based on the baseline 24-hdietary recalls, the Mg treatment used a personalized dose of Mg supplementation that would reduce the calcium (Ca): Mg intake ratio to around 2.3. We measured plasma MCFAs, sugars, ketone bodies and tricarboxylic acid cycle (TCA cycle) metabolites using the Metabolon's global Precision Metabolomics™ LC-MS platform. Whole-genome shotgun metagenomics (WGS) sequencing was performed to assess microbiota in stool samples, rectal swabs, and rectal biopsies. Personalized Mg treatment (mean dose 205.58mg/day with a range from 77.25to 389.55mg/day) significantly increased the plasma levels of C7:0, C8:0, and combined C7:0 and C8:0 by 18.45%, 25.28%, and 24.20%, respectively, compared to 14.15%, 10.12%, and 12.62% decreases in the placebo arm. The effects remain significant after adjusting for age, sex, race and baseline level (P=0.0126, P=0.0162, and P=0.0031, respectively) and FDR correction at 0.05 (q=0.0324 for both C7:0 and C8:0). Mg treatment significantly reduced the plasma level of sucrose compared to the placebo arm (P=0.0036 for multivariable-adjusted and P=0.0216 for additional FDR correction model) whereas alterations in daily intakes of sucrose, fructose, glucose, maltose and C8:0 from baseline to the end of trial did not differ between two arms. Mediation analysis showed that combined C7:0 and C8:0 partially mediated the effects of Mg treatment on total and individual ketone bodies (P for indirect effect=0.0045, 0.0043, and 0.03, respectively). The changes in plasma levels of C7:0 and C8:0 were significantly and positively correlated with the alterations in stool microbiome α diversity (r=0.51, p=0.0023 and r=0.34, p=0.0497, respectively) as well as in stool abundance for the signatures of MCFAs-related microbiota with acyl-ACP thioesterase gene producing C7:0 (r=0.46, p=0.0067) and C8:0 (r=0.49, p=0.003), respectively, following Mg treatment. Optimizing Ca:Mg intake ratios to around 2.3 through 12-week personalized Mg supplementation leads to increased circulating levels of MCFAs (i.e. C7:0 and C8:0), which is attributed to enhanced production from gut microbial fermentation and, maybe, sucrose consumption.

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day

Sucrose intake by rats affected by both intraperitoneal oxytocin administration and time of day

Peroxisome Proliferator-Activated Receptor α Has a Protective Effect on Fatty Liver Caused by Excessive Sucrose Intake.

Sterol regulatory element binding protein (SREBP)-1c is a transcription factor that regulates lipid synthesis from glucose in the liver. It is activated by sucrose, which activates the fatty acid synthesis pathway. On the other hand, peroxisome proliferator-activated receptor (PPAR) α regulates the transcription of several genes encoding enzymes involved in fatty acid β-oxidation in the liver. To evaluate the beneficial effects of PPARα on fatty liver caused by excessive sucrose intake, we investigated the molecular mechanisms related to the development of fatty liver in PPARα-deficient mice that were fed a high-sucrose diet (Suc). The SREBP-1c target gene expression was increased by sucrose intake, leading to the development of fatty liver. Furthermore, PPARα−/− mice developed severe fatty liver. Male and female PPARα−/− mice fed Suc showed 3.7- and 3.1-fold higher liver fat content than Suc-fed male and female wild-type mice, respectively. Thus, PPARα may work to prevent the development of fatty liver caused by excessive sucrose intake. Liver TG accumulation differed between male and female PPARα−/− mice. A possible explanation is that male mice show the increased expression of Pparγ, which usually contributes to triglyceride synthesis in the liver, to compensate for Pparα deficiency. In contrast, female wild-type mice inherently have low Pparα levels. Thus, Pparα deficiency has less pronounced effects in female mice. A diet that activates PPARα may be effective for preventing the development of fatty liver due to excessive sucrose intake.

Plasma Nesfatin Responses Following a Single Session of Interval Exercise in Young Men: Effects of Glucose, Sucrose and Fructose Intake

Plasma Nesfatin Responses Following a Single Session of Interval Exercise in Young Men: Effects of Glucose, Sucrose and Fructose Intake

Responses Of Adipocytokines And Insulin Following A High-dose Sucrose Intake And Exercise

Responses Of Adipocytokines And Insulin Following A High-dose Sucrose Intake And Exercise

Metabolic Fate and Expectation of Health Benefits of [U-<sup>14</sup>C]-Sucrose Inhibited from Digestion Using <i>Morus alba</i> Leaf Extract

Morus alba leaf extract (MLE), a strong inhibitor of sucrase, suppresses blood glucose elevation following sucrose ingestion. To investigate that sucrose inhibited from digestion using MLE is utilized through gut microbiota, [U-14C]-sucrose solutions with or without MLE were administered orally to conventional and antibiotic-treated rats, and the excretion of 14CO2 and H2 produced by gut microbiota was measured for 24 h. After an administration of [U-14C]-sucrose to conventional rats, the unit excreted 14CO2 peaked at 4 h, and the cumulative 14CO2 excreted over 24 h was approximately 60% of the radioactivity administered. No H2 was excreted. Following an administration of [U-14C]-sucrose and MLE in conventional rats, the unit excreted 14CO2 peaked later, at 8 h, and was significantly lower (p<0.05). The cumulative 14CO2 excreted over 24 h was equal in both groups, although there was a time lag of 2-3 h in rats given [U-14C]-sucrose and MLE. The amount of H2 excreted by these rats peaked 8 h after administration. Following the administration of [U-14C]-sucrose and MLE to antibiotic-treated rats, the unit excreted 14CO2 peaked lower, and the cumulative 14CO2 excretion over 24 h was approximately 40%. In this group, H2 was minimally excreted. H2 and 14CO2 produced by gut microbiota were excreted simultaneously. In conclusion, sucrose inhibited from digestion using MLE was fermented spontaneously by gut microbiota and was not excreted into feces. In addition, it confirmed that H2 excretion could be used directly to indicate the degree of fermentation of nondigestible carbohydrates.

Stress resilience-associated behaviors following predator scent stress are accompanied by upregulated nucleus accumbens mGlu5 transcription in female Sprague Dawley rats

Despite the higher prevalence of post-traumatic stress disorder (PTSD) in women, the majority of preclinical research has been conducted utilizing male subjects. We have found that male rats exposed to the predator scent 2,4,5-trimethyl-3-thiazoline (TMT) show heterogenous long-term anxiety-like behavior and conditioned fear to the TMT environment. Stress-Resilient males exhibit increased mGlu5 mRNA expression in the basolateral amygdala (BLA) and prefrontal cortex (PFC). Here we sought to determine whether the same behavioral and genetic responses would be observed in female rats exposed to TMT. Female Sprague-Dawley rats were exposed to TMT for ten minutes, while Controls were exposed to an unscented environment. Anxiety and anhedonia were assessed 7–14 days later with elevated plus maze (EPM), acoustic startle response, light-dark box, and sucrose preference test (SPT). TMT-exposed females spent less time in the EPM open arms, exhibited greater startle amplitude, and reduced sucrose intake compared to Controls. Median split analyses conducted on EPM and SPT data yielded stress-Susceptible and -Resilient phenotypes that displayed behavior in the light-dark box consistent with EPM and SPT behavior. Susceptible females displayed greater BLA mGlu5 mRNA expression than Resilient and Control rats and did not show conditioned fear, in contrast to previous results in males. Resilient females displayed greater mGlu5 mRNA expression in the nucleus accumbens. These data indicate that the predator scent stress model of PTSD produces distinct stress-Susceptible and Resilient phenotypes in female rats that are associated with changes in mGlu5 mRNA expression in several brain regions.

Effects of chronic psychosocial stress on ‘binge-like’ sucrose intake in mice

Binge eating episodes are persistent and are essential features of numerous eating disorders (EDs). Susceptibility to EDs is largely presumed to be associated with early life stress. In fact, converging evidence from preclinical animal studies have implicated stress as a driver of binge eating. Still, literature examination indicates that vulnerability to EDs may depend on factors such as severity, time, and the type of stressor. Therefore, we aimed at exploring the link between chronic psychosocial stress and ‘binge-like’ sucrose intake in adolescent mice. To this aim, intruders' experimental mice were exposed to the chronic subordinate colony (CSC) housing, in the presence of a resident aggressive mouse for 2 weeks. At the end of the stress period, mice were tested for anxiety-like behavior then assessed for ‘binge-like’ intake of sucrose using a long-term drinking in the dark (DID) method that successfully replicates binge eating in humans. As expected, and compared to single housed colony controls (SHC), CSC exposure elicited an anxiogenic-like response in the open field (OF) and elevated-plus maze (EPM) tests and reduced weight gain. Most importantly, we report here for the first time, that mice exposed to chronic psychosocial stress displayed a ‘binge-like’ consumption of sucrose. However, neither quinine (bitter) nor saccharin (sweet) intakes were affected by CSC exposure. Finally, using Pearson's correlation, results showed a strong correlation between anxiety-like behavior parameters and sucrose intake. Overall these findings support the validity of our chronic psychosocial stress to model binge EDs and establish the long-term consequences of stress on ‘binge-like’ eating in male mice. These data suggest that chronic psychosocial stress is a risk factor for developing anxiety-associated EDs.