Aspartame, as an artificial sweetener, does not affect renal function and antioxidative states in mice.

BACKGROUND AND OBJECTIVE: Aspartame (L-aspartyl L-phenylalanine methyl ester) is an artificial sweetener widely used as a sugar substitute. There are concerns regarding the effects of high aspartame doses on the kidney owing to oxidative stress; however, whether the maximum allowed dose of aspartame in humans affects the kidneys remains unknown. Therefore, in this study, we investigated whether the maximum allowed dose of aspartame in humans affects the kidneys. METHODS: In this study, animals were fed a folate-deficient diet to mimic human aspartame metabolism. Eight-week-old ICR mice were divided into control (CTL), 40 mg/kg/day of aspartame-administered (ASP), folate-deficient diet (FD), and 40 mg/kg/day of aspartame-administered with a folate-deficient diet (FD + ASP) groups. Aspartame was administered orally for eight weeks. Thereafter, we evaluated aspartame's effect on kidneys via histological analysis. RESULTS: There were no differences in serum creatinine and blood urea nitrogen levels between the CTL and ASP groups or between the FD and FD + ASP groups. There was no histological change in the kidneys in any group. The expression of superoxide dismutase and 4-hydroxy-2-nonenal in the kidney did not differ between the CTL and ASP groups or the FD and FD + ASP groups. CONCLUSION: Our findings indicate that the allowed doses of aspartame in humans may not affect kidney function or oxidative states.

Neural responses to oral administration of erythritol vs. sucrose and sucralose explain differences in subjective liking ratings.

INTRODUCTION: High sugar intake is associated with many chronic diseases. However, non-caloric sweeteners (NCSs) might fail to successfully replace sucrose due to the mismatch between their rewarding sweet taste and lack of caloric content. The natural NCS erythritol has been proposed as a sugar substitute due to its satiating properties despite being non-caloric. We aimed to compare brain responses to erythritol vs. sucrose and the artificial NCS sucralose in a priori taste, homeostatic, and reward brain regions of interest (ROIs). METHODS: We performed a within-subject, single-blind, counterbalanced fMRI study in 30 healthy men (mean ± SEM age:24.3 ± 0.8 years, BMI:22.3 ± 0.3 kg/m2). Before scanning, we individually matched the concentrations of both NCSs to the perceived sweetness intensity of a 10% sucrose solution. During scanning, participants received 1 mL sips of the individually titrated equisweet solutions of sucrose, erythritol, and sucralose, as well as water. After each sip, they rated subjective sweetness liking. RESULTS: Liking ratings were significantly higher for sucrose and sucralose vs. erythritol (both pHolm = 0.0037); water ratings were neutral. General Linear Model (GLM) analyses of brain blood oxygen level-depended (BOLD) responses at qFDR<0.05 showed no differences between any of the sweeteners in a priori ROIs, but distinct differences were found between the individual sweeteners and water. These results were confirmed by Bayesian GLM and machine learning-based models. However, several brain response patterns mediating the differences in liking ratings between the sweeteners were found in whole-brain multivariate mediation analyses. Both subjective and neural responses showed large inter-subject variability. CONCLUSION: We found lower liking ratings in response to oral administration of erythritol vs. sucrose and sucralose, but no differences in neural responses between any of the sweeteners in a priori ROIs. However, differences in liking ratings between erythritol vs. sucrose or sucralose are mediated by multiple whole-brain response patterns.

Glucose appetition in C57BL/6J mice: Influence of nonnutritive sweetener experience, food deprivation state and sex differences.

In addition to its sweet taste, glucose has potent and rapid postoral actions (appetition) that enhance its reward value. This has been demonstrated by the experience-induced preference for glucose over initially preferred nonnutritive sweetener solutions in 24-h choice tests. However, some sweetener solutions (e.g., 0.8% sucralose) have inhibitory postoral actions that may exaggerate glucose appetition whereas others (e.g., 0.1% sucralose + 0.1% saccharin, S+S) do not. Experiment 1 revealed that food-restricted (FR) male C57BL/6J mice displayed similar rapid glucose appetition effects (stimulation of glucose licking within minutes) and conditioned flavor preferences following 1-h experience with flavored 0.8% sucralose or 0.1% S+S and 8% glucose solutions. Thus, the inhibitory effects of 0.8% sucralose observed in 24-h tests were not apparent in 1-h tests. Experiment 2 evaluated the effects of food deprivation state and sweetener concentration on glucose appetition in female mice. Unlike FR mice tested with 0.1% S+S and 8% glucose, ad libitum (AL) fed mice displayed no stimulation of 8% glucose licking in the 1-h tests. A second ad libitum group (AL) tested with 0.2% S+S and 16% glucose solutions displayed stimulation of 16% glucose licking by the third 1-h test. Both AL groups, like the FR group, developed a preference for the glucose-paired flavor over the S+S paired flavor. Thus, food restriction promotes increased glucose licking but is not required for a conditioned preference. The FR male mice (Exp. 1) and FR female mice (Exp. 2) showed similar appetition responses (licking stimulation and flavor preference) to 8% glucose.

Daytime aspartame intake results in larger influences on body weight, serum corticosterone level, serum/cerebral cytokines levels and depressive-like behaviors in mice than nighttime intake.

Aspartame (APM) is one of the most widely used artificial sweeteners worldwide. Studies have revealed that consuming APM may negatively affect the body, causing oxidative stress damage to multiple organs and leading to various neurophysiological symptoms. However, it's still unclear if consuming APM and one's daily biological rhythm have an interactive effect on health. In this study, healthy adult C57BL/6 mice were randomly divided into four groups: Control group (CON), oral gavage sham group (OGS), daytime APM intragastric group (DAI) and nighttime APM intragastric group (NAI). DAI and NAI groups were given 80 mg/kg body weight daily for 4 weeks. We found that DAI and NAI groups had significantly increased mean body weight, higher serum corticosterone levels, up-regulated pro-inflammatory responses in serum and brain, and exacerbated depressive-like behaviors than the CON and the two APM intake groups. Moreover, all these changes induced by APM intake were more significant in the DAI group than in the NAI group. The present study, for the first time, revealed that the intake of APM and daily biological rhythm have an interactive effect on health. This suggests that more attention should be paid to the timing of APM intake in human beings, and this study also provides an intriguing clue to the circadian rhythms of experimental animals that researchers should consider more when conducting animal experiments.

Assessing the relationship between low-calorie sweetener use and quality of life measures in adults with type 1 diabetes.

BACKGROUND: To evaluate use of low-calorie sweeteners (LCS) among adults with type 1 diabetes (T1D) and its impact on quality of life (QOL). METHODS: In this single center, cross-sectional survey study with 532 adults with T1D, Food related QOL (FRQOL), LCS specific questionnaire (LCSSQ), Diabetes Self-Management Questionnaire (DSMQ), Food Frequency Questionnaire (FFQ), Audit of Diabetes-Dependent QOL (AddQOL), Type 1 Diabetes and Life (T1DAL) questionnaires were administered through RedCAP, a secure, HIPAA-compliant web-based application. Demographics and scores of adults who used LCS in last month (recent users) and others (non-users) were compared. Results were adjusted for age, sex, diabetes duration and other parameters. RESULTS: Of 532 participants (mean age 36 ± 13, 69% female), 99% heard LCS before, 68% used them in the last month, 73% reported better glucose control with LCS use and 63% reported no health concerns about LCS use. Recent LCS users were older and had a longer diabetes duration and more complications (hypertension, or any complication) than non-users. However, A1c, AddQOL, T1DAL, FRQOL scores did not differ significantly between recent LCS users and non-users. DSMQ scores, DSMQ management, diet, health care scores did not differ between two groups; however, recent LCS users had lower physical activity score than non-users (p = 0.001). CONCLUSIONS: Most of the adults with T1D have used LCS and perceived that LCS use improved their QOL and glycemic control; however, these were not verified with questionnaires. There was no difference in QOL questionnaires except DSMQ physical activity between recent LCS users and not users with T1D. However, more patients in need to increase their QOL may be using LCS; therefore, associations between the exposure and outcome can be bi-directional.

The dietary sweetener sucralose is a negative modulator of T cell-mediated responses.

Artificial sweeteners are used as calorie-free sugar substitutes in many food products and their consumption has increased substantially over the past years1. Although generally regarded as safe, some concerns have been raised about the long-term safety of the consumption of certain sweeteners2-5. In this study, we show that the intake of high doses of sucralose in mice results in immunomodulatory effects by limiting T cell proliferation and T cell differentiation. Mechanistically, sucralose affects the membrane order of T cells, accompanied by a reduced efficiency of T cell receptor signalling and intracellular calcium mobilization. Mice given sucralose show decreased CD8+ T cell antigen-specific responses in subcutaneous cancer models and bacterial infection models, and reduced T cell function in models of T cell-mediated autoimmunity. Overall, these findings suggest that a high intake of sucralose can dampen T cell-mediated responses, an effect that could be used in therapy to mitigate T cell-dependent autoimmune disorders.

Rapid fluctuations in brain oxygenation during glucose-drinking behavior in trained rats.

Proper inflow of oxygen into brain tissue is essential for maintaining normal neural functions. Although oxygen levels in the brain's extracellular space depend upon a balance between its delivery from arterial blood and its metabolic consumption, the use of high-speed electrochemical detection revealed rapid increases in brain oxygen levels elicited by various salient sensory stimuli. These stimuli also increase intrabrain heat production, an index of metabolic neural activation, but these changes are slower and more prolonged than changes in oxygen levels. Therefore, under physiological conditions, the oxygen inflow into brain tissue exceeds its loss due to consumption, thus preventing any metabolic deficit. Here, we used oxygen sensors coupled with amperometry to examine the pattern of real-time oxygen fluctuations in the nucleus accumbens during glucose-drinking behavior in trained rats. Following the exposure to a glucose-containing cup, oxygen levels rapidly increased, peaked when the rat initiated drinking, and relatively decreased during consumption. Similar oxygen changes but more episodic drinking occurred when Stevia, a calorie-free sweet substance, was substituted for glucose. When water was substituted for glucose, rats tested the water but refused to consume all of it. Although the basic pattern of oxygen changes during this water test was similar to that with glucose drinking, the increases were larger. Finally, oxygen increases were significantly larger when rats were exposed to concealed glucose and made multiple unsuccessful attempts to obtain and consume it. Based on these data, we discuss the mechanisms underlying behavior-related brain oxygen fluctuations and their functional significance.NEW & NOTEWORTHY Oxygen sensors coupled with high-speed amperometry were used to examine brain oxygen fluctuations during glucose-drinking behavior in trained rats. Oxygen levels rapidly increased following presentation of a glucose-contained cup, peaking at the initiation of glucose drinking, and relatively decreasing during drinking. Oxygen increases were larger when rats were exposed to concealed glucose and made multiple attempts to obtain it. We discuss the mechanisms underlying behavior-related brain oxygen fluctuations and their functional significance.

Low- and no-calorie sweetener intakes in the Brazilian population estimated using added sugar substitution modelling.

This research examined the intakes of six low- and no-calorie sweeteners (LNCS) (acesulfame-K, aspartame, cyclamate, saccharin, steviol glycosides, and sucralose) by the Brazilian population using an added sugar substitution approach. Detailed exposure modelling requires the use of proprietary concentration data, which can be difficult to obtain. Two exposure models were conducted using nationally representative food consumption data. The first model ('per person') estimated added sugar intakes on an individual person basis, replacing 50% of added sugar intakes >10% total energy with each LNCS considering sucrose sweetness equivalence. The second model ('per food') replaced 50% of the added sugar content in foods and beverages with each LNCS, incorporating sucrose sweetness equivalence and Brazilian tonnage data. Both models predicted that intakes would be below the JECFA ADI for five of the six LNCS in all population groups examined (≥10 years) for average and heavy consumers. For cyclamate, exceedance of the ADI was determined for all age groups amongst heavy consumers in the 'per person' model, while estimated intakes in the 'per food' model were below or reached the ADI for the cohort. Additional research is needed for younger age groups to confirm whether these findings are applicable to the entire Brazilian population.

Hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada: a population-based retrospective cohort study.

BACKGROUND: People with diabetes mellitus commonly experience hypoglycemia, but they may not necessarily present to hospital after severe hypoglycemia requiring paramedic assistance. We sought to describe the incidence and characteristics of calls for hypoglycemia requiring paramedic assistance among adults in southwestern Ontario, Canada, and to determine predictors of hospital transport. METHODS: This population-based retrospective cohort study used data extracted from ambulance call reports (ACRs) of 8 paramedic services of the Southwest Ontario Regional Base Hospital Program from January 2008 to June 2014. We described calls in which treatment for hypoglycemia was administered, summarized the incidence of hypoglycemia calls and performed logistic regression to determine predictors of hospital transport. RESULTS: Out of 470 467 ACRs during the study period, 9185 paramedic calls occurred in which hypoglycemia treatment was administered to an adult (mean age 60.2 yr, 56.8% male, 81.1% with documented diabetes). Refusal of hospital transport occurred in 2243 (24.4%) of calls. Documented diabetes diagnosis (adjusted odds ratio [OR] 0.82, 95% confidence interval [CI] 0.69-0.96), higher capillary blood glucose (adjusted OR 0.31, 95% CI 0.22-0.44) and overnight calls (adjusted OR 0.80, 95% CI 0.72-0.91) were associated with lower odds of hospital transport. Higher-acuity calls (adjusted OR 2.05, 95% CI 1.58-2.66) were associated with higher odds of transport. The estimated annual incidence rate of hypoglycemia requiring paramedic assistance was 108 per 10 000 people with diabetes per year. INTERPRETATION: Hypoglycemia requiring paramedic assistance in southwestern Ontario is common, and close to 25% of calls do not result in hospital transport. Physicians managing diabetes care may be unaware of patients' hypoglycemia requiring paramedic care, suggesting a potential gap in follow-up care; we suggest that paramedics play an important role in identifying those at high recurrence risk and communicating with their care providers.

Association between Sugar-Sweetened Beverage Consumption and Executive Function in Children.

The association between sugar-sweetened beverages (SSB) and executive function among children has been less investigated. We aimed to explore this topic. We randomly recruited 6387 children aged 6-12 years from five elementary schools in Guangzhou, China in 2019. Information on frequency and servings of children's SSB consumption was assessed using a questionnaire. Children's executive function was evaluated using parents' ratings of the Behavioral Rating Inventory of Executive Function (BRIEF), which comprises eight subscales-including inhibit, shift, emotional control, initiate, working memory, plan/organize, organization of materials and monitor, as well as three composite indexes including behavioral regulation index (BRI), metacognition index (MI), and global executive index (GEC). SSB consumption was positively associated with all subscales and composite scores of BRIEF as well as higher risks of elevated executive difficulties, indicating poorer executive function. For example, children who drank SSB ≥2 times/week were related to higher scores of GEC (estimates, 95% confidence interval (CI): 2.44, 1.79 to 3.09) compared with those who never drank SSB. The odds ratio of elevated GEC associated with SSB consumption ≥2 times/week was 1.62 (95% CI: 1.34, 1.96) than non-consumers. The results of this study indicated that SSB consumption was associated with poorer executive function in children.

Assessment of Glycemic Response to Model Breakfasts Varying in Glycemic Index (GI) in 5-7-Year-Old School Children.

Reduced Glycemic Index (GI) of breakfast has been linked to improved cognitive performance in both children and adult populations across the morning. However, few studies have profiled the post-prandial glycemic response (PPGR) in younger children. The aim of this study was to assess PPGR to breakfast interventions differing in GI in healthy children aged 5-7 years. Eleven subjects completed an open-label, randomized, cross-over trial, receiving three equicaloric test beverages (260 kcal) consisting of 125 mL semi-skimmed milk and 50 g sugar (either glucose, sucrose, or isomaltulose). On a fourth occasion, the sucrose beverage was delivered as intermittent supply. PPGR was measured over 180 min using Continuous Glucose Monitoring (CGM). The incremental area under the curve (3h-iAUC) was highest for the glucose beverage, followed by intermittent sucrose (-21%, p = 0.288), sucrose (-27%, p = 0.139), and isomaltulose (-48%, p = 0.018). The isomaltulose beverage induced the smallest Cmax (7.8 mmol/L vs. >9.2 mmol/L for others) and the longest duration with moderate glucose level, between baseline value and 7.8 mmol/L (150 vs. <115 min for others). These results confirm that substituting mid-high GI sugars (e.g., sucrose and glucose) with low GI sugars (e.g., isomaltulose) during breakfast are a viable strategy for sustained energy release and glycemic response during the morning even in younger children.

Acute Metabolic Responses to Glucose and Fructose Supplementation in Healthy Individuals: A Double-Blind Randomized Crossover Placebo-Controlled Trial.

The aim of this study was to investigate the impact of glucose (Glu), fructose (Fru), glucose and fructose (GluFru) and sucralose on blood glucose response in healthy individuals. Fifteen healthy individuals (five females, age of 25.4 ± 2.5 years, BMI of 23.7 ± 1.7 kg/m2 with a body mass (BM) of 76.3 ± 12.3 kg) participated in this double-blind randomized crossover placebo-controlled trial. Participants received a mixture of 300 mL of water with 1 g/kg BM of Glu, 1 g/kg BM of Fru, 0.5 g/kg BM of GluFru (each), and 0.2 g sucralose as a placebo. Peak BG values Glu were reached after 40 ± 13 min (peak BG: 141 ± 20 mg/dL), for Fru after 36 ± 22 min (peak BG: 98 ± 7 mg/dL), for GluFru after 29 ± 8 min (BG 128 ± 18 mg/dL), and sucralose after 34 ± 27 min (peak BG: 83 ± 5 mg/dL). Significant differences regarding the time until peak BG were found only between Glu and GluFru supplementation (p = 0.02). Peak blood glucose levels were significantly lower following the ingestion of Fru compared to the supplementation of Glu and GluFru (p < 0.0001) while Glu and GluFru supplementation showed no difference in peak values (p = 0.23). All conditions led to a significantly higher peak BG value compared to sucralose (p < 0.0001). Blood lactate increased in Glu (p = 0.002), Fru and GluFru (both p < 0.0001), whereas sucralose did not increase compared to the baseline (p = 0.051). Insulin levels were significantly higher in all conditions at peak compared to sucralose (p < 0.0001). The findings of this study prove the feasibility of combined carbohydrate supplementations for many applications in diabetic or healthy exercise cohorts.

Maternal sucralose exposure induces Paneth cell defects and exacerbates gut dysbiosis of progeny mice.

Research has shown that maternal sucralose (MS) exposure alters the gut microbiota of offspring at weaning and predisposes the offspring to developing obesity, non-alcoholic fatty liver disease and metabolic syndrome later in life. However, the underlying mechanism remains unclear. Paneth cells are thought to critically influence the gut microbiota. This study aimed to investigate whether MS exposure induced Paneth cell defects and exacerbated gut dysbiosis of offspring. Female C57BL/6 mice were divided into the MS and control (water) groups during pregnancy and lactation. Progeny mice were fed a normal sucralose-free diet after weaning until adulthood. MS inhibited intestinal development and increased the expression of proinflammatory cytokines in the small intestines of 3-week-old progeny mice. MS increased the proportions of abnormal granule secretion by Paneth cells. The number of Paneth cells and mRNA expression of AMPs such as cryptdins and lysozyme were reduced in the MS group. MS disturbed the gut microbiota composition and diversity in the 3-week-old offspring mice. The relative abundances of pro-inflammatory bacteria, such as Desulfovibrionales, Helicobacter, Pasteurellales and Campylobacterales were significantly increased in the MS group, while anti-inflammatory bacteria, including Clostridium XI, were decreased. This dysbiosis continued into adulthood. These findings showed that MS exposure induced Paneth cell defects and exacerbated gut dysbiosis in offspring mice. Sucralose should be consumed with caution, especially during pregnancy and in early life.

Management of asymptomatic hypoglycemia with 40% oral dextrose gel in near term at-risk infants to reduce intensive care need and promote breastfeeding.

BACKGROUND: Neonatal hypoglycemia is a common disorder especially in at-risk infants and it can be associated with poor long-term neurological outcomes. Several therapeutic interventions are suggested, from the implementation of breastfeeding to the glucose intravenous administration. Oral dextrose gel massaged into the infant's inner cheek is a recent treatment option of asymptomatic hypoglycemia, after which oral feeding is encouraged. This approach seems to reduce the admission of infants to neonatal intensive care unit (NICU) so favouring maternal bonding and breastfeeding success at discharge. METHODS: In our ward, we prospectively compared a group of near-term neonates, (Gr2, n = 308) at risk for hypoglycemia, treated with an innovative protocol based on the addition of 40% oral dextrose gel (Destrogel, Orsana®,Italy) administered by massaging gums and cheek with historical matching newborns (Gr1, n = 389) treated with a formerly used protocol, as control group. The primary outcome was occurrence of NICU admission and the requirement of intravenous glucose administration; while discharge with full breastfeeding was the secondary outcome. RESULTS: In Gr1, 39/389 (10%) infants presented with asymptomatic hypoglycemia, 19/39 were transferred to the NICU, and 14/39 required intravenous glucose treatment. In Gr2, among the 30/308 infants with asymptomatic hypoglycemia managed according to the new protocol, 3/30 were transferred to the NICU and received intravenous glucose infusion. The mean duration of hospitalization respectively was 6.43 (± 6.36) and 3.73 ± 1.53 days (p <  0.001). At discharge, 7.7% of the infants in Gr1 and 30% of the infants in Gr2 were exclusively breastfed (p = 0.02). Considering Gr1 vs Gr2, the number of patients that were transferred to NICU was 19 (48.7%) vs 3 (10%) (p = 0.001) and the number of infants that needed intravenous glucose infusion was 14 (35.9%) vs 3 (10%) (p = 0.01), respectively. CONCLUSIONS: In our population of near term infants, the introduction of 40% oral dextrose gel to the protocol, helped in the safe management of asymptomatic hypoglycemia and, at the same time, implemented breastfeeding.

Analysis of Caloric and Noncaloric Sweeteners Present in Dairy Products Aimed at the School Market and Their Possible Effects on Health.

Over the past decades, Mexico has become one of the main sweetener-consuming countries in the world. Large amounts of these sweeteners are in dairy products aimed at the children's market in various presentations such as yogurt, flavored milk, flan, and cheeses. Although numerous studies have shown the impact of sweeteners in adults, the current evidence for children is insufficient and discordant to determine if these substances have any risk or benefit on their well-being. Therefore, this study aimed to describe the sweeteners present in 15 dairy products belonging to the school-age children's market in Mexico and their impact on health. These dairy products were selected through a couple of surveys directed at parents of school-age children. After that, the list of ingredients of each product was analyzed to identify their sweetener content. From there, exhaustive bibliographic research on sweeteners and their possible health effects was carried out, which included 109 articles and 18 studies. The results showed that at a neurological, endocrinological, cardiovascular, metabolic, osseous, renal, hepatic, dental, reticular, carcinogenic, and gut microbiota level; sucrose, fructose, high-fructose corn syrup, maltodextrins, sucralose, and acesulfame K, have a negative effect. While maltodextrins, stevia, polydextrose, and modified starch have a positive one. For these reasons, it is necessary to evaluate the advantages and disadvantages that the consumption of each sweetener entails, as well as a determination of the appropriate acceptable daily intake (ADI).

Short-Term High Fructose Intake Impairs Diurnal Oscillations in the Murine Cornea.

Purpose: Endogenous and exogenous stressors, including nutritional challenges, may alter circadian rhythms in the cornea. This study aimed to determine the effects of high fructose intake (HFI) on circadian homeostasis in murine cornea. Methods: Corneas of male C57BL/6J mice subjected to 10 days of HFI (15% fructose in drinking water) were collected at 3-hour intervals over a 24-hour circadian cycle. Total extracted RNA was subjected to high-throughput RNA sequencing. Rhythmic transcriptional data were analyzed to determine the phase, rhythmicity, unique signature, metabolic pathways, and cell signaling pathways of transcripts with temporally coordinated expression. Corneas of HFI mice were collected for whole-mounted techniques after immunofluorescent staining to quantify mitotic cell number in the epithelium and trafficking of neutrophils and γδ-T cells to the limbal region over a circadian cycle. Results: HFI significantly reprogrammed the circadian transcriptomic profiles of the normal cornea and reorganized unique temporal and clustering enrichment pathways, but did not affect core-clock machinery. HFI altered the distribution pattern and number of corneal epithelial mitotic cells and enhanced recruitment of neutrophils and γδ-T cell immune cells to the limbus across a circadian cycle. Cell cycle, immune function, metabolic processes, and neuronal-related transcription and associated pathways were altered in the corneas of HFI mice. Conclusions: HFI significantly reprograms diurnal oscillations in the cornea based on temporal and spatial distributions of epithelial mitosis, immune cell trafficking, and cell signaling pathways. Our findings reveal novel molecular targets for treating pathologic alterations in the cornea after HFI.

Disruption of lateral hypothalamic calorie detection by a free choice high fat diet.

During the last few decades, the consumption of low-calorie sweeteners, as a substitute for caloric sweeteners, has sharply increased. Although research shows that caloric versus low-calorie sweeteners can have differential effects on the brain, it is unknown which neuronal populations are responsible for detecting the difference between the two types of sweeteners. Using in vivo two-photon calcium imaging, we investigated how drinking sucrose or sucralose (a low-calorie sweetener) affects the activity of glutamatergic neurons in the lateral hypothalamus. Furthermore, we explored the consequences of consuming a free-choice high fat diet on the calorie detection abilities of these glutamatergic neurons. We found that glutamatergic neurons indeed can discriminate sucrose from water and sucralose, and that consumption of a free-choice high fat diet shifts the glutamatergic neuronal response from sucrose-specific to sucralose-specific, thereby disrupting calorie detection. These results highlight the disruptive effects of a diet high in saturated fat on calorie detection in the lateral hypothalamus.

Inactivation of posterior but not anterior dorsomedial caudate-putamen impedes learning with self-administered nicotine stimulus in male rats.

The rodent caudate-putamen is a large heterogeneous neural structure with distinct anatomical connections that differ in their control of learning processes. Previous research suggests that the anterior and posterior dorsomedial caudate-putamen (a- and p-dmCPu) differentially regulate associative learning with a non-contingent nicotine stimulus. The current study used bilateral NMDA-induced excitotoxic lesions to the a-dmCPu and p-dmCPu to determine the functional involvement of a-dmCPu and p-dmCPu in appetitive learning with contingent nicotine stimulus. Rats with a-dmCPu, p-dmCPu, or sham lesions were trained to lever-press for intravenous nicotine (0.03 mg/kg/inf) followed by access to sucrose 30 s later. After 1, 3, 9, and 20 nicotine-sucrose training sessions, appetitive learning in the form of a goal-tracking response was assessed using a non-contingent nicotine-alone test. All rats acquired nicotine self-administration and learned to retrieve sucrose from a receptacle at equal rates. However, rats with lesions to p-dmCPu demonstrated blunted learning of the nicotine-sucrose association. Our primary findings show that rats with lesions to p-dmCPu had a blunted goal-tracking response to a non-contingent nicotine administration after 20 consecutive days of nicotine-sucrose pairing. Our findings extend previous reports to a contingent model of nicotine self-administration and show that p-dmCPu is involved in associative learning with nicotine stimulus using a paradigm where rats voluntarily self-administer nicotine infusions that are paired with access to sucrose-a paradigm that closely resembles learning processes observed in humans.

Pancreastatin mediated regulation of UCP-1 and energy expenditure in high fructose fed perimenopausal rats.

AIMS: Pancreastatin (PST) is a crucial bioactive peptide derived from chromogranin A (CHGA) proprotein that exhibits an anti-insulin effect on adipocytes. Herein, we investigated the effects of PST on brown adipose tissues (BAT) and white adipose tissue (WAT) in connection with uncoupling protein-1 (UCP-1) regulated energy expenditure in high fructose diet (HFrD) fed and vinylcyclohexenediepoxide (VCD) induced perimenopausal rats. MATERIAL AND METHODS: We administered VCD in rats for 17 consecutive days and fed HFrd for 12 weeks. After 12 weeks estradiol and progesterone levels were detected. Furthermore, detection of glucose tolerance, insulin sensitivity, and body composition revealed impaired glucose homeostasis and enhanced PST levels. Effects of enhanced PST on UCP-1 level in BAT and WAT of perimenopausal rats were further investigated. KEY FINDINGS: Reduced serum estradiol, progesterone, and attenuated insulin response confirmed perimenopausal model development. Furthermore, enhanced PST serum level and its increased expression in BAT and WAT downregulated the UCP-1 expression. Subsequently, impaired ATP level, NADP/NADPH ratio, citrate synthase activity, enhanced mitochondrial reactive oxygen species (ROS) generation and perturbed mitochondrial membrane potential, further exacerbated mitochondrial dysfunction, cellular ROS production, and promoted apoptosis. Interestingly, PST inhibition by PST inhibitor peptide-8 (PSTi8) displayed a favorable impact on UCP-1 and energy expenditure. SIGNIFICANCE: The aforementioned outcomes indicated the substantial role of PST in altering the UCP-1 expression and associated energy homeostasis. Hence our results corroborate novel avenues to unravel the quest deciphering PST's role in energy homeostasis and its association with perimenopause.