Food Intake Research Articles

Subthreshold activation of the melanocortin system causes generalized sensitization to anorectic agents in mice.

The melanocortin-3 receptor (MC3R) regulates GABA release from agouti-related protein (AgRP) nerve terminals and thus tonically suppresses multiple circuits involved in feeding behavior and energy homeostasis. Here, we examined the role of the MC3R and the melanocortin system in regulating the response to various anorexigenic agents. The genetic deletion or pharmacological inhibition of the MC3R, or subthreshold doses of an MC4R agonist, improved the dose responsiveness to glucagon-like peptide 1 (GLP1) agonists, as assayed by inhibition of food intake and weight loss. An enhanced anorectic response to the acute satiety factors peptide YY (PYY3-36) and cholecystokinin (CCK) and the long-term adipostatic factor leptin demonstrated that increased sensitivity to anorectic agents was a generalized result of MC3R antagonism. We observed enhanced neuronal activation in multiple hypothalamic nuclei using Fos IHC following low-dose liraglutide in MC3R-KO mice (Mc3r-/-), supporting the hypothesis that the MC3R is a negative regulator of circuits that control multiple aspects of feeding behavior. The enhanced anorectic response in Mc3r-/- mice after administration of GLP1 analogs was also independent of the incretin effects and malaise induced by GLP1 receptor (GLP1R) analogs, suggesting that MC3R antagonists or MC4R agonists may have value in enhancing the dose-response range of obesity therapeutics.

An atlas of GPCRs in dopamine neurons: Identification of the free fatty acid receptor 4 as a regulator of food and water intake

Midbrain dopaminergic neurons (DANs) are subject to extensive metabotropic regulation, but the repertoire of G protein-coupled receptors (GPCRs) present in these neurons has not been mapped. Here, we isolate DANs from Dat-eGFP mice to generate a GPCR atlas by unbiased qPCR array expression analysis of 377 GPCRs. Combined with data mining of scRNA-seq databases, we identify multiple receptors in DAN subpopulations with 38 of these receptors representing the majority of transcripts. We identify 41 receptors expressed in midbrain DANs but not in non-DAN midbrain cells, including the free fatty acid receptor 4 (FFAR4). Functional expression of FFAR4 is validated by exvivo Ca2+ imaging, and invivo experiments support that FFAR4 negatively regulates food and water intake and bodyweight. In addition to providing a critical framework for understanding metabotropic DAN regulation, our data suggest fatty acid sensing by FFAR4 as a mechanism linking high-energy intake to the dopamine-reward pathway.

Ultra-processed food consumption and risk of diabetes: results from a population-based prospective cohort.

Understanding the impact of the overall construct of ultra-processed foods on diabetes risk can inform dietary approaches to diabetes prevention. In this study, we aimed to evaluate the association between ultra-processed food consumption and risk of diabetes in a community-based cohort of middle-aged adults in the USA. We hypothesised that a higher intake of ultra-processed foods is associated with a higher risk of incident diabetes. The study included 13,172 participants without diabetes at baseline (1987-1989) in the Atherosclerosis Risk in Communities (ARIC) study. Dietary intake was assessed with a 66-item semiquantitative food frequency questionnaire, and foods were categorised by processing level using the Nova classification system. Ultra-processed food was analysed categorically (quartiles of energy-adjusted intake) and continuously (per one additional serving/day). We used Cox regression to evaluate the association of ultra-processed food intake with risk of diabetes with adjustment for sociodemographic characteristics, total energy intake, health behaviours and clinical factors. Over a median follow-up of 21 years, there were 4539 cases of incident diabetes. Participants in the highest quartile of ultra-processed food intake (8.4 servings/day on average) had a significantly higher risk of diabetes (HR 1.13; 95% CI 1.03, 1.23) compared with participants in the lowest quartile of intake after adjustment for sociodemographic, lifestyle and clinical factors. Each additional serving of ultra-processed food consumed daily was associated with a 2% higher risk of diabetes (HR 1.02; 95% CI 1.00, 1.04). Highest quartile consumption of certain ultra-processed food groups, including sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks, was associated with a 29%, 21% and 16% higher risk of diabetes, respectively, compared with the lowest quartile. We found that a higher intake of ultra-processed food was associated with higher risk of incident diabetes, particularly sugar- and artificially sweetened beverages, ultra-processed meats and sugary snacks. Our findings suggest interventions reducing ultra-processed food consumption and specific food groups may be an effective strategy for diabetes prevention.

Elemental Diet as a Therapeutic Modality: A Comprehensive Review.

Elemental diets have been employed for the management of various diseases for over 50years, with several mechanisms mediating their beneficial effects. Yet, they are underutilized due to poor palatability, access, cost, and lack of awareness regarding their clinical efficacy. Therefore, in this review, we aimed to systematically search and review the literature to summarize the formulation variability, mechanisms of action, clinical applications, and tolerability of the elemental diets in gastrointestinal diseases. While large prospective trials are lacking, elemental diets appear to exhibit objective and subjective clinical benefit in several diseases, including eosinophilic esophagitis, eosinophilic gastroenteritis, inflammatory bowel diseases, small intestinal bacterial overgrowth,intestinal methanogen overgrowth, chemoradiotherapy-associated mucositis, and celiac disease. Although some data support the long-term use of elemental diets as an add-on supplement for chronic pancreatitis and Crohn's disease, most of the literature on exclusive elemental diets focuses on inducing remission. Therefore, subsequent treatment strategies for maintaining remission need to be adopted in chronic/relapsing diseases. Several mechanistic pathways were identified to mediate the effects of elemental diets, including food additive and allergen-free content, high passive absorption rate, and anti-inflammatory properties. High rates of intolerance up to 40% are seen in the trials where exclusive elemental diets were administered orally due to poor organoleptic acceptability; however, when tolerated, adverse events were rare. Other limitations of elemental diets are cost, access, and lifestyle/social restrictions. Moreover, judicious use is advised in presence of a concomitant restrictive food intake disorders. Elemental diets offer a potentially highly efficacious dietary intervention with minor side effects. Palatability, cost, access, and social restrictions are common barriers of use. Prospective clinical trials are needed to elucidate the role of elemental formulas in the management of individual diseases.

27-Hydroxycholesterol acts on estrogen receptor α expressed by POMC neurons in the arcuate nucleus to modulate feeding behavior.

Oxysterols are metabolites of cholesterol that regulate cholesterol homeostasis. Among these, the most abundant oxysterol is 27-hydroxycholesterol (27HC), which can cross the blood-brain barrier. Because 27HC functions as an endogenous selective estrogen receptor modulator, we hypothesize that 27HC binds to the estrogen receptor α (ERα) in the brain to regulate energy balance. Supporting this view, we found that delivering 27HC to the brain reduced food intake and activated proopiomelanocortin (POMC) neurons in the arcuate nucleus of the hypothalamus (POMCARH) in an ERα-dependent manner. In addition, we observed that inhibiting brain ERα, deleting ERα in POMC neurons, or chemogenetic inhibition of POMCARH neurons blocked the anorexigenic effects of 27HC. Mechanistically, we further revealed that 27HC stimulates POMCARH neurons by inhibiting the small conductance of the calcium-activated potassium (SK) channel. Together, our findings suggest that 27HC, through its interaction with ERα and modulation of the SK channel, inhibits food intake as a negative feedback mechanism against a surge in circulating cholesterol.

The relationship between dietary habits and menstruation problems in women: a cross-sectional study

BackgroundNutrition is important to the management and relief of the symptoms in menstrual disorders. This study aims to investigate the relationship between menstrual disorders and specific foods and nutrient intake in women.MethodsFive-hundred-nine menstruating women participated in the study. The questionnaire form was created by the researchers via Google Forms and distributed in online applications (WhatsApp, Instagram etc.). The questionnaire consists of 5 sections, including demographic data, declared anthropometric measurements (height (m or cm), weight (g or kg)), questions about eating habits, menstruation status, and 24-hour food consumption. Statistical analysis was made with SPSS 23; nutrient analysis of food consumption was made using BeBiS 9.0.ResultsIt was found that the body mass index (BMI) of healthy participants was higher than women with menstrual disorders. Women with menstrual disorders have lower intake of protein, vitamin K, vitamin B3, vitamin B5 and sodium compared with healthy women. All participants have a higher intake of vitamin B3, sodium, phosphorus, and manganese, and have a lower intake of other nutrients compared with the national adequate intake.ConclusionOur findings showed that women with menstrual disorders consume more high-sugar food/beverages and have inadequate nutrients intake.

The dual amylin and calcitonin receptor agonist KBP-336 elicits a unique combination of weight loss, antinociception and bone protection – a novel disease-modifying osteoarthritis drug

BackgroundDespite the extensive research to provide a disease-modifying osteoarthritis drug (DMOAD), there is still no approved DMOAD. Dual amylin and calcitonin receptor agonists (DACRA) can provide metabolic benefits along with antinociceptive and potential structural preserving effects. In these studies, we tested a DACRA named KBP-336 on a metabolic model of OA in meniscectomised (MNX) rats.MethodsWe evaluated KBP-336’s effect on pain-like symptoms in Sprague Dawley (SD) rats on high-fat diet (HFD) that underwent meniscectomy using the von Frey test to measure the 50% paw withdrawal threshold (PWT) and analyzed using one-way ANOVA. Short in vivo studies and in vitro cell receptor expression systems were used to illustrate receptor pharmacology.ResultsAfter 30 weeks on HFD, including an 8-week treatment, female MNX animals receiving KBP-336 4.5 nmol/Kg/72 h had lower body weight and smaller adipose tissues than their vehicle-treated counterparts. After 20 weeks on HFD, including an 8-week treatment, male rats receiving KBP-336 had lower body weight than the vehicle group. In both the female and male rats, the MNX groups on KBP-336 treatment had a higher PWT than the vehicle-treated MNX group. Aiming to identify the receptor influencing pain alleviation, KBP-336 was compared to the long-acting human calcitonin (hCTA). Single-dose studies on 12-week-old male rats showed that hCTA lowers CTX-I without affecting food intake, confirming its calcitonin receptor selectivity. On the metabolic OA model with 18 weeks of HFD, including 6-week treatment, hCTA at 100 nmol/Kg/24 h and KBP-336 at 0.5, 1.5, and 4.5 nmol/Kg/72 h produced significantly higher PWT in MNX animals compared to MNX animals on vehicle treatment. hCTA and KBP-336 at 0.5 nmol/Kg did not affect body weight and fat tissues.ConclusionOverall, KBP-336 improved the pain observed in the metabolic OA model. Calcitonin receptor activation proved to be essential in this antinociceptive effect.

Impact of replacing protein pellets with soybean grain on nutrient utilization and the rumen and blood parameters of feedlot cattle under tropical conditions.

The aim of this study was to explore the effect of replacing protein pellets with soybean grain in high-concentrate diets with or without the addition of silage, on the intake, digestibility, and rumen and blood parameters of feedlot cattle in tropical regions. Four cannulated, crossbred steers were used, 4.5 ± 0.5 years old, with an average weight of 685.55 ± 111.78kg. The steers were distributed in a 4 × 4 Latin square, in a 2 × 2 factorial scheme (two sources of protein: protein pellets or whole soybean grain, with or without added dietary bulk). There was no effect (P ≥ 0.109) from the interaction between the source of protein and the addition of silage to the diet on dry matter (DM) and nutrient intake, or the digestibility (P ≥ 0.625) of DM or crude protein (CP). However, both factors affected (P ≤ 0.052) the intake of DM, neutral detergent fiber (NDF), and non-fiber carbohydrates (NFC), as well as the independent digestibility (P ≤ 0.099) of fat, NFC, total carbohydrates (TC), and total cholesterol concentration. There was an effect (P ≤ 0.053) from the interaction between the source of protein and the addition of silage to the diet on the digestibility of NDF and total digestible nutrients (TDN), as well as on the glycose concentration (P = 0.003). Blood parameters (i.e. protein, albumin, creatinine, triglycerides, aspartate aminotransferase (AST), and alanine aminotransferase (ALT)) were not affected (P ≥ 0.139) by the source of protein, the addition of silage, or their interaction. Lastly, including 150g/kg silage DM in a high-grain diet, and using soybean grain as a source of protein in substitution of protein pellet could be a suitable nutritional strategy to ensure adequate DM and nutrient intake and digestibility, with no detrimental effects on rumen and blood parameters of feedlot cattle in the tropics.

Comparison of dietary patterns and daily food intake across kidney disease stages in England: a-posteriori cluster analysis

ObjectiveDietary patterns are rapidly becoming a major focus of medical nutrition therapy in CKD and the analysis of dietary patterns has emerged as a practical approach to evaluate qualitative as well as quantitative aspects of overall diet. In an a-posteriori data-driven approach, dietary patterns are based on the actual food intake of the population evaluated. Investigation of dietary patterns in CKD are not well described, and, to our knowledge, have not been conducted in a UK-based cohort. MethodsAdult participants with a diagnosed kidney condition (CKD 1-5 not requiring dialysis) were recruited into a multi-centre observational cross-sectional study. Dietary intake was assessed using the European Prospective Investigation of Cancer in Norfolk Food Frequency Questionnaire. Logistic Principal Components Analysis was used to identify food group clusters. Differences between groups were assessed using univariate general linear modelling. ResultsIn total, 696 patients were included. The mean age was 64.7 (±14.0) years, 61% of the cohort were male. Most participants were White British (89%). The mean eGFR was 36.6 (±20.9) ml/min/1.732. We found differences in food group intake across stages (e.g., greater intake of nuts and seeds intake in CKD 1-2 versus CKD 4) and across sex (e.g., females had a higher intake of fruit and vegetables versus males). Comparison with the reference cohort revealed that, overall, the CKD cohort had reduced intakes of food stuffs such as cereals and cereal products, but higher intakes of groups such as meat and meat products. There were limited differences in micronutrients, although Vitamin B2 and calcium were higher in earlier stages. ConclusionOverall, the findings from a novel a-posteriori approach underline the complex diversity of food patterns in CKD. The findings from our study may inform dieticians and other healthcare providers about the need to consider treatment modalities and stages when giving dietary recommendations.

Hypothalamic and hippocampal transcriptome changes in AppNL-G-F mice as a function of metabolic and inflammatory dysfunction

The progression of Alzheimer’s disease (AD) has a silent phase that predates characteristic cognitive decline and eventually leads to active cognitive deficits. Metabolism, diet, and obesity have been correlated to the development of AD but is poorly understood. The hypothalamus is a brain region that exerts homeostatic control on food intake and metabolism and has been noted to be impacted during the active phase of Alzheimer’s disease. This study, in using an amyloid overexpression AppNL-G-F mouse model under normal metabolic conditions, examines blood markers in young and old male AppNL-G-F mice (n = 5) that corresponds to the silent and active phases of AD, and bulk gene expression changes in the hypothalamus and the hippocampus. The results show a large panel of inflammatory mediators, leptin, and other proteins that may be involved in weakening the blood brain barrier, to be increased in the young AppNL-G-F mice but not in the old AppNL-G-F mice. There were also several differentially expressed genes in both the hypothalamus and the hippocampus in the young AppNL-G-F mice prior to amyloid plaque formation and cognitive decline that persisted in the old AppNL-G-F mice, including GABRa2 receptor, Wdfy1, and several pseudogenes with unknown function. These results suggests that a larger panel of inflammatory mediators may be used as blood markers to detect silent AD, and that a change in leptin and gene expression in the hypothalamus exist prior to cognitive effects, suggesting a coupling of metabolism with amyloid plaque induced cognitive decline.

Effects of Universal School-Based Parental Support for Children's Healthy Diet and Physical Activity-the Healthy School Start Plus Cluster-Randomised Controlled Trial.

Health promotion from an early age is key to preventing unhealthy weight development in childhood, and parental involvement is essential. The school-based Healthy School Start intervention aims to promote healthy dietary and activity habits in the home environment and prevent child obesity through parental support. This study evaluated the effectiveness of the third iteration of the programme on children's dietary and activity behaviours, and body composition through a cluster-randomised controlled trial. The trial included 17 schools (8 intervention) in disadvantaged areas in mid-Sweden with 353 families with 5- to 7-year-old children. The primary outcomes were intake of selected healthy and unhealthy foods and beverages measured using photography. Secondary outcomes were physical activity and sedentary time measured by accelerometry, and measured weight and height. All outcomes were assessed at baseline and post-intervention (8months). Linear multi-level regression showed significant favourable effects of the intervention for intake of sweet beverages (b = - 0.17, p = 0.04), intake of healthy foods (b = 0.11, p = 0.04), and more time in moderate to vigorous physical activity during weekdays (b = 5.68, p = 0.02). An unfavourable sub-group effect of the intervention was found for children from families with low education regarding sedentary time on weekends (b = 23.04, p = 0.05). The results align with the previous two trials of the programme, indicating that school-based parental support is a useful approach for health promotion in young children in disadvantaged areas. Trial registration: ClinicalTrials.gov: No. NCT03390725, retrospectively registered on January 4, 2018, https://clinicaltrials.gov/ct2/show/NCT03390725 .

Outcome of Severe Acute Malnutrition in Children Aged 6-59 Months Before and After the Institution of the Malnutrition Treatment Centre in the Regional Hospital Limbe, Southwest Region of Cameroon

Background: Malnutrition occurs when nutrient and energy intake do not meet, or exceed an individual’s requirements to maintain growth, immunity, and organ function. In 2020, among children 0-59 months worldwide, 21.3% (144 million) were stunted and 6.9% (47 million) were wasted. The Malnutrition Treatment Centre’s (MTC) establishment in the Regional Hospital Limbe in 2019 brought major changes in management such as free and continuous supply of therapeutic food and basic drugs, the expertise of a nutritionist and closer follow up of patients after discharge. The aim of this research was to evaluate the outcome of children with severe acute malnutrition aged 6-59 months treated at the MTC differed from those treated before the MTC’s creation. Methodology: An analytic cross sectional retrospective study was conducted from February to March 2022. The study period was from March 2016 to February 2019 (before the MTC) and March 2019 to February 2022 (after the MTC). A predesigned data extraction form was used to obtain sociodemographic data of the children and their parents, clinical findings on admission and hospital outcome. The data was entered into CDC Epi info 2.4 and analysed using SPSS. A p-value of <0.05 was considered statistically significant. Results: Out of 129 files included in the study, 35 were pre-MTC and 94 after its creation. The hospital prevalence of SAM increased from 4% to 7% after the MTC’s creation. The mean MUAC (mid-upper arm circumference) was 11.1 ± 0.98 cm. Marasmus was the most common form of SAM (90.7%). The most common admission symptoms were fever (74.4%), diarrhoea (47.2%) and vomiting (32.6%). The most common comorbidities were malaria (29.5%), gastrointestinal infection (20.9%), sepsis (18.6%) and pulmonary infection (14%). There was an increase in the recovery rate (from 71.4% to 76.6%) and the rate of weight gain (from 3.5 g/kg/day to 8.7 g/kg/day). There was also a reduction in the death rate (from 14.3% to 9.6%) and length of in-hospital admission (from 10.24 ±5.4 days to 7.3 ±3.6 days) Conclusion: The MTC led to an increase in the influx of patients with SAM at the RHL, marasmus was the most common form of SAM. There was an increase in the rate of weight gain, a decreased mortality rate and decreased length of hospital stay, thus revealing the pertinent relevance of the MTC in the management of SAM.

Outcome of Severe Acute Malnutrition in Children Aged 6-59 Months Before and After the Institution of the Malnutrition Treatment Centre in the Regional Hospital Limbe, Southwest Region of Cameroon

Background: Malnutrition occurs when nutrient and energy intake do not meet, or exceed an individual’s requirements to maintain growth, immunity, and organ function. In 2020, among children 0-59 months worldwide, 21.3% (144 million) were stunted and 6.9% (47 million) were wasted. The Malnutrition Treatment Centre’s (MTC) establishment in the Regional Hospital Limbe in 2019 brought major changes in management such as free and continuous supply of therapeutic food and basic drugs, the expertise of a nutritionist and closer follow up of patients after discharge. The aim of this research was to evaluate the outcome of children with severe acute malnutrition aged 6-59 months treated at the MTC differed from those treated before the MTC’s creation. Methodology: An analytic cross sectional retrospective study was conducted from February to March 2022. The study period was from March 2016 to February 2019 (before the MTC) and March 2019 to February 2022 (after the MTC). A predesigned data extraction form was used to obtain sociodemographic data of the children and their parents, clinical findings on admission and hospital outcome. The data was entered into CDC Epi info 2.4 and analysed using SPSS. A p-value of <0.05 was considered statistically significant. Results: Out of 129 files included in the study, 35 were pre-MTC and 94 after its creation. The hospital prevalence of SAM increased from 4% to 7% after the MTC’s creation. The mean MUAC (mid-upper arm circumference) was 11.1 ± 0.98 cm. Marasmus was the most common form of SAM (90.7%). The most common admission symptoms were fever (74.4%), diarrhoea (47.2%) and vomiting (32.6%). The most common comorbidities were malaria (29.5%), gastrointestinal infection (20.9%), sepsis (18.6%) and pulmonary infection (14%). There was an increase in the recovery rate (from 71.4% to 76.6%) and the rate of weight gain (from 3.5 g/kg/day to 8.7 g/kg/day). There was also a reduction in the death rate (from 14.3% to 9.6%) and length of in-hospital admission (from 10.24 ±5.4 days to 7.3 ±3.6 days) Conclusion: The MTC led to an increase in the influx of patients with SAM at the RHL, marasmus was the most common form of SAM. There was an increase in the rate of weight gain, a decreased mortality rate and decreased length of hospital stay, thus revealing the pertinent relevance of the MTC in the management of SAM.

Formative research to understand food beliefs and practices relating to pregnancy on Kei Besar Island, Eastern Indonesia

BackgroundFood-related beliefs and practices during pregnancy may contribute to the high prevalence of chronic energy deficiencies (CED) in Eastern Indonesia, particularly in Southeast Maluku regency, where 21.33% of pregnant women experience CED. Currently, little information on these issues is available. This study investigates food beliefs and practices related to pregnancy on Kei Besar Island in the Maluku province of Eastern Indonesia.MethodsA qualitative study was conducted utilizing in-depth interviews, free lists, and pile sort exercises. Data collection was conducted in January 2023 and involved married pregnant women aged 18 and above (n = 12), community health volunteers (n = 2), and traditional healers (n = 3) from 9 villages in Kei Besar District. All participants must be natives of Kei Besar Island, with community health volunteers and traditional healers being respective figures recommended by the local villagers.ResultsThe need to avoid or minimize consumption of certain foods during pregnancy, such as some kinds of fish, chili and spicy food, soda, pineapples, octopus, squid, and ice was reported by more than one-third of all participants. Consumption of prescribed foods, such as cassava leaves, papaya, coconut water, rice during early pregnancies, moringa leaves, bananas, and katok leaves was reported by five or more participants. These food proscriptions and prescriptions were due to concerns about the risks of miscarriage, adverse effects on the fetus and mother, and complications during labor. Participants also reported other practices, such as eating for two during early pregnancy and reducing food intake in late pregnancy. We found that food beliefs have shaped the dietary patterns of most participants. However, they still consumed food recommended by community health volunteers and midwives.ConclusionsFood beliefs are present and practiced in the Kei Besar community and may impact the nutritional status of women and their infants. Interventions should target training healthcare providers and community health volunteers to provide culturally appropriate health education that incorporates prescribed local ingredients and provides nutritionally adequate substitutes for the proscribed food items.Trial RegistrationNot applicable.

The effect of underlying diseases on pneumonia risk in patients with neurogenic or tumor-related dysphagia: a retrospective cohort study.

To analyze the association of neurological disorders (ND) and head and neck cancer (HNC) with dysphagia severity and aspiration pneumonia occurrence. Retrospective cohort study conducted at a university dysphagia center) for two consecutive years. Patients with ND or HNC were included if they had undergone a flexible endoscopic swallowing evaluation (FEES) at the dysphagia center, and at least one food consistency had been sampled and recorded. Outcomes of interest were swallowing safety, highest penetration-aspiration-score (PASmax), way of food intake, presence of a tracheal tube, and occurrence of pneumonia within the past two years. Of 257 consecutive patients, 199 were enrolled in the study and classified according to their underlying diagnosis into ND (120 patients) or HNC (79 patients). Forty-three HNC patients (54.4%) and 54 ND patients (45%) showed critical dysphagia in FEES (PAS ≥ 6). Binary logistic regression comparing both groups showed patients with ND to be 2.31 times more likely to develop pneumonia. However, if the 32 stroke patients were excluded from the calculation, PASmax remains the only significant variable affecting pneumonia risk in both groups. Liquids were the main challenge for ND patients, while aspirating HNC patients struggled with all consistencies. The study shows that patients with HNC and ND differ in pneumonia risk only if stroke patients are included in the ND group. If they are excluded, the PAS score is the only remaining risk factor for pneumonia. Thickening liquids may not be suitable for all dysphagic patients; individually tailored measures might be more helpful, especially for HNC patients.

Dissociable hindbrain GLP1R circuits for satiety and aversion.

The most successful obesity therapeutics, glucagon-like peptide-1 receptor (GLP1R) agonists, cause aversive responses such as nausea and vomiting1,2, effects that may contribute to their efficacy. Here, we investigated the brain circuits that link satiety to aversion, and unexpectedly discovered that the neural circuits mediating these effects are functionally separable. Systematic investigation across drug-accessible GLP1R populations revealed that only hindbrain neurons are required for the efficacy of GLP1-based obesity drugs. In vivo two-photon imaging of hindbrain GLP1R neurons demonstrated that most neurons are tuned to either nutritive or aversive stimuli, but not both. Furthermore, simultaneous imaging of hindbrain subregions indicated that area postrema (AP) GLP1R neurons are broadly responsive, whereas nucleus of the solitary tract (NTS) GLP1R neurons are biased towards nutritive stimuli. Strikingly, separate manipulation of these populations demonstrated that activation of NTSGLP1R neurons triggers satiety in the absence of aversion, whereas activation of APGLP1R neurons triggers strong aversion with food intake reduction. Anatomical and behavioural analyses revealed that NTSGLP1R and APGLP1R neurons send projections to different downstream brain regions to drive satiety and aversion, respectively. Importantly, GLP1R agonists reduce food intake even when the aversion pathway is inhibited. Overall, these findings highlight NTSGLP1R neurons as a population that could be selectively targeted to promote weight loss while avoiding the adverse side effects that limit treatment adherence.

THE EFFECT OF SUB-CLINICAL INFECTION WITH HAEMONCHUS CONTORTUS ON PRODUCTION PERFORMANCE IN THE ‎PREGNANT EWES

Fourteen Bulgarian pregnant ewes (three months of gestation), were used and divided in two groups, one group was inoculated with 500 infective larvae /kg. body weight, the other group remained non-infected control. Productive parameters, blood changes were recorded and faecal egg counts were examined weekly. Marked reduction in food intake was recorded in infected ewes, especially during prelambing period. No obvious differences were noted between both groups after lambing. Slight differences in body weight gain were recorded between both groups until labour, while after lambing, the weight losses of infected ewes were highly significant 1%. No effect of infection has been seen on fleece weight, while significant depression in the haemoglobin and packed cell volum of infected group during the pre-parturient period, and the high reduction occured at week (7). Generally the results indicated that there were variations in resistance of ewes or its susceptibility to parasitic infection.

Comparative analysis of energy homeostasis regulation at different altitudes in Hengduan Mountain of red-backed vole, Eothenomys miletus, during high-fat diet acclimation: examining gut microbial and physiological interactions

The study aimed to explore the similarities and differences in gut microorganisms and their functions in regulating body mass in Eothenomys miletus across different altitudes in the Hengduan Mountains when exposed to a high-fat diet. Eothenomys miletus specimens were gathered from Dali (DL) and Xianggelila (XGLL) in Yunnan Province, China, and categorized into control, high-fat (1 week of high-fat diet), and re-feeding groups (1 week of high-fat diet followed by 2 weeks of standard food). The analysis utilized 16S rRNA sequencing to assess the diversity and structure of intestinal microbial communities in E. miletus. The investigation focused on the impact of high-fat diet consumption and different altitudes on gut microbial diversity, structure, and physiological markers. Results revealed that a high-fat diet influenced the beta diversity of gut microorganisms in E. miletus, leading to variations in microbial community structure between the two regions with different altitudes. High-fat food significantly affected body mass, white adipose tissue mass, triglycerides, and leptin levels, but not food intake. Specific intestinal microorganisms were observed in the high-fat groups, aiding in food digestion and being enriched in particular flora. In particular, microbial genera like Lactobacillus and Hylemonella were enriched in the high-fat group of DL. The enriched microbiota in the control group was associated with plant polysaccharide and cellulose decomposition. Following a high-fat diet, gut microbiota adapted to support lipid metabolism and energy supply, while upon re-feeding, the focus shifted back to cellulose digestion. These findings suggested that alterations in gut microbial composition, alongside physiological markers, play a vital role in adaptation of E. miletus to the diverse habitats of the Hengduan Mountains at varying altitudes.

HcGr76 responds to fructose and chlorogenic acid and is involved in regulation of peptide expression in the midgut of Hyphantria cunea larvae.

Sensing dietary components in the gut is important to ensure an appropriate hormonal response and metabolic regulation after food intake. The fall webworm, Hyphantria cunea, is a major invasive pest in China and has led to significant economic losses and ecosystem disruption. The larvae's broad host range and voracious appetite for leaves make H. cunea a primary cause of serious damage to both forests and crops. To date, however, the gustatory receptors (Grs) of H. cunea and their regulatory function remain largely unknown. We identified the fall webworm gustatory receptor HcGr76 as a fructose and chlorogenic acid receptor using Ca2+ imaging and determination of intracellular Ca2+ concentration by a microplate reader. Moreover, reverse transcription-quantitative polymerase chain reaction (RT-qPCR) analysis revealed that HcGr76 is highly expressed in the anterior and middle midgut. Knockdown of HcGr76 caused a significant reduction in the expression of neuropeptide F 1 (NPF1) and CCHamide-2, and led to a decrease in carbohydrate and lipid levels in the hemolymph. Our studies provide circumstantial evidence that HcGr76 expressed in the midgut is involved in sensing dietary components, and regulates the expression of relevant peptide hormones to alter metabolism in H. cunea larvae, thus providing a promising molecular target for the development of new insect-specific control products. © 2024 Society of Chemical Industry.

MicroRNA-21 modulates brown adipose tissue adipogenesis and thermogenesis in a mouse model of polycystic ovary syndrome

BackgroundPolycystic ovary syndrome (PCOS), the most common endocrine disorder in premenopausal women, is associated with increased obesity, hyperandrogenism, and altered brown adipose tissue (BAT) thermogenesis. MicroRNAs play critical functions in brown adipocyte differentiation and maintenance. We aim to study the role of microRNA-21 (miR-21) in altered energy homeostasis and BAT thermogenesis in a PCOS mouse model of peripubertal androgen exposure.MethodsThree-week-old miR-21 knockout (miR21KO) or wild-type (WT) female mice were treated with dihydrotestosterone (DHT) or vehicle for 90 days. Body composition was determined by EchoMRI. Energy expenditure (EE), oxygen consumption (VO2), carbon dioxide production (VCO2), and respiratory exchange ratio (RER) were measured by indirect calorimetry. Androgen receptor (AR), and markers of adipogenesis, de novo lipogenesis, angiogenesis, extracellular matrix remodeling, and thermogenesis were quantified by RT-qPCR and/or Western-blot.ResultsMiR-21 ablation attenuated DHT-mediated increase in body weight while having no effect on fat or BAT mass. MiR-21 ablation attenuated DHT-mediated BAT AR upregulation. MiR-21 ablation did not alter EE; however, miR21KO DHT-treated mice have reduced VO2, VCO2, and RER. MiR-21 ablation reversed DHT-mediated decrease in food intake and increase in sleep time. MiR-21 ablation decreased some adipogenesis (Adipoq, Pparγ, and Cebpβ) and extracellular matrix remodeling (Mmp-9 and Timp-1) markers expression in DHT-treated mice. MiR-21 ablation abolished DHT-mediated increases in thermogenesis markers Cpt1a and Cpt1b, while decreasing CIDE-A expression.ConclusionsOur findings suggest that BAT miR-21 may play a role in regulating DHT-mediated thermogenic dysfunction in PCOS. Modulation of BAT miR-21 levels could be a novel therapeutic approach for the treatment of PCOS-associated metabolic derangements.