Deletion of the Clock Gene Bmal2 Leads to Alterations in Hypothalamic Clocks, Circadian Regulation of Feeding, and Energy Balance.

BMAL2 (ARNTL2) is a paralog of BMAL1 that can form heterodimers with the other circadian factors CLOCK and NPAS2 to activate transcription of clock and clock-controlled genes. To assess a possible role of Bmal2 in the circadian regulation of metabolism, we investigated daily variations of energy metabolism, feeding behavior, and locomotor behavior, as well as ability to anticipate restricted food access in male mice knock-out for Bmal2 (B2KO). While their amount of food intake and locomotor activity were normal compared with wild-type mice, B2KO mice displayed increased adiposity (1.5-fold higher) and fasted hyperinsulinemia (fourfold higher) and tended to have lower energy expenditure at night. Impairment of the master clock in the suprachiasmatic nuclei was evidenced by the shorter free-running period (-14 min/cycle) of B2KO mice compared with wild-type controls and by a loss of daily rhythmicity in expression of intracellular metabolic regulators (e.g., Lipoprotein lipase and Uncoupling protein 2). The circadian window of eating was longer in B2KO mice. The circadian patterns of food intake and meal numbers were bimodal in control mice but not in B2KO mice. In response to restricted feeding, food-anticipatory activity was almost prevented in B2KO mice, suggesting altered food clock that controls anticipation of food availability. In the mediobasal hypothalamus of B2KO mice, expression of genes coding orexigenic neuropeptides (including Neuropeptide y and Agouti-Related Peptide) was downregulated, while Lipoprotein lipase expression lost its rhythmicity. Together, these data highlight that BMAL2 has major impacts on brain regulation of metabolic rhythms, sleep-wake cycle, and food anticipation.

Activation of the G protein-coupled sulfakinin receptor inhibits blood meal intake in the mosquito Aedes aegypti.

Little is known about the blood-feeding physiology of arbovirus vector Aedes aegypti although this type of mosquito is known to transmit infectious diseases dengue, Zika, yellow fever, and chikungunya. Blood feeding in the female A. aegypti mosquito is essential for egg maturation and for transmission of disease agents between human subjects. Here, we identify the A. aegypti sulfakinin receptor gene SKR from the A. aegypti genome and show that SKR is expressed at different developmental stages and in varied anatomical localizations in the adult mosquito (at three days after eclosion), with particularly high expression in the CNS. Knockingdown sulfakinin and sulfakinin receptor gene expression in the female A. aegypti results in increased blood meal intake, but microinjection in the thorax of the sulfakinin peptide 1 and 2 both inhibits dose dependently blood meal intake (and delays the time course of blood intake), which is reversible with receptor antagonist. Sulfakinin receptor expressed ectopically in mammalian cells CHO-K1 responds to sulfakinin stimulation with persistent calcium spikes, blockable with receptor antagonist. These data together suggest that activation of the Gq protein-coupled (i.e., calcium-mobilizing) sulfakinin receptor inhibits blood meal intake in female A. aegypti mosquitoes and could serve as a strategic node for the future control of A. aegypti mosquito reproduction/population and disease transmission.

Analyzing postprandial metabolomics data using multiway models: a simulation study.

BACKGROUND: Analysis of time-resolved postprandial metabolomics data can improve the understanding of metabolic mechanisms, potentially revealing biomarkers for early diagnosis of metabolic diseases and advancing precision nutrition and medicine. Postprandial metabolomics measurements at several time points from multiple subjects can be arranged as a subjects by metabolites by time points array. Traditional analysis methods are limited in terms of revealing subject groups, related metabolites, and temporal patterns simultaneously from such three-way data. RESULTS: We introduce an unsupervised multiway analysis approach based on the CANDECOMP/PARAFAC (CP) model for improved analysis of postprandial metabolomics data guided by a simulation study. Because of the lack of ground truth in real data, we generate simulated data using a comprehensive human metabolic model. This allows us to assess the performance of CP models in terms of revealing subject groups and underlying metabolic processes. We study three analysis approaches: analysis of fasting-state data using principal component analysis, T0-corrected data (i.e., data corrected by subtracting fasting-state data) using a CP model and full-dynamic (i.e., full postprandial) data using CP. Through extensive simulations, we demonstrate that CP models capture meaningful and stable patterns from simulated meal challenge data, revealing underlying mechanisms and differences between diseased versus healthy groups. CONCLUSIONS: Our experiments show that it is crucial to analyze both fasting-state and T0-corrected data for understanding metabolic differences among subject groups. Depending on the nature of the subject group structure, the best group separation may be achieved by CP models of T0-corrected or full-dynamic data. This study introduces an improved analysis approach for postprandial metabolomics data while also shedding light on the debate about correcting baseline values in longitudinal data analysis.

Fasting as an intervention to alter the impact of simulated night-shift work on glucose metabolism in healthy adults: a cluster randomised controlled trial.

AIMS/HYPOTHESIS: Night-shift work causes circadian misalignment and impairs glucose metabolism. We hypothesise that food intake during night shifts may contribute to this phenomenon. METHODS: This open-label, multi-arm, single-site, parallel-group controlled trial involved a 6 day stay at the University of South Australia's sleep laboratory (Adelaide, SA, Australia). Healthy, non-shift-working adults without obesity (N=55; age 24.5 ± 4.8 years; BMI 24.8 ± 2.8 kg/m2) were assigned to the next available run date and cluster randomised (1:1:1) to fasting-at-night (N=20), snack-at-night (N=17), or meal-at-night (N=18) conditions. One participant withdrew from each group, prior to starting the study. Due to study design, neither participants nor people collecting their measurements could be blinded. Statistical and laboratory staff were concealed to study allocation. Participants were fed at calculated energy balance, with the macronutrient composition of meals being similar across conditions. The primary outcomes were a linear mixed-effects model of glucose, insulin and NEFA AUC in response to a 75 g OGTT that was conducted prior to and after 4 consecutive nights of shift work plus 1 night of recovery sleep. Insulin sensitivity, insulinogenic and disposition indexes were also calculated. RESULTS: Night-shift work impaired insulin sensitivity, as measured by insulin AUC (p=0.035) and the insulin sensitivity index (p=0.016) across all conditions. Insulin secretion, as measured by the insulinogenic index, was increased in the fasting-at-night condition only (p=0.030), resulting in a day×condition interaction in glucose AUC (p<0.001) such that glucose tolerance was impaired in the meal-at night (+2.00 [95% CI 1.45, 2.56], p<0.001) and snack at-night (+0.96 [0.36, 1.56], p=0.022) conditions vs the fasting-at-night (+0.34 [-0.21, 0.89]) condition. A day×condition interaction was also observed in NEFA AUC (p<0.001), being higher in the meal-at-night (+0.07 [0.03, 0.10]. p=0.001) and snack-at-night (0.01 [-0.03, 0.05], p=0.045) conditions vs the fasting-at-night condition (-0.02 [-0.06, 0.01]). No adverse events occurred. CONCLUSIONS/INTERPRETATION: The timing of food intake has a critical effect on glucose metabolism during simulated night-shift work, which was readily amendable to a meal re-timing intervention. TRIAL REGISTRATION: Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12616001556437 FUNDING: This work was funded by the National Health and Medical Research Council (NHMRC), APP1099077.

Exploring the longitudinal expression dynamics of midguts in adult female Amblyomma americanum ticks.

BACKGROUND: Female ticks remain attached to their host for multiple days to complete a blood meal. This prolonged feeding period is accompanied by a significant increase in the tick's size and body weight, paralleled by noteworthy changes to the tick midgut. While the midgut is recognized for its established role in blood storage and processing, its importance extends to playing a crucial role in the acquisition, survival, and proliferation of pathogens. Despite this, our overall understanding of tick midgut biology is limited. RESULTS: Our transcriptome analysis identified 15,599 putative DNA coding sequences (CDS), which were classified into 26 functional groups. Dimensional and differential expression analyses revealed four primary transcriptional profiles corresponding to unfed, slow-feeding, transitory (from slow- to rapid-feeding), and rapid-feeding stages. Additionally, comparing the current dataset with previously deposited transcriptome from other tick species allowed the identification of commonly expressed transcripts across different feeding stages. CONCLUSION: Our findings provide a detailed temporal resolution of numerous metabolic pathways in the midgut of A. americanum adult females throughout the feeding process, highlighting the dynamic transcriptional regulation of the tick's midgut as feeding progresses. Furthermore, we identified conserved transcripts across three different tick species that exhibit similar expression patterns. This knowledge not only enhances our understanding of the physiological processes within the tick midgut but also opens up potential avenues for developing control methods that target multiple tick species.

Duration of morning hyperinsulinemia determines hepatic glucose uptake and glycogen storage later in the day.

The second-meal phenomenon refers to the improvement in glucose tolerance seen following a second identical meal. We previously showed that 4 h of morning hyperinsulinemia, but not hyperglycemia, enhanced hepatic glucose uptake (HGU) and glycogen storage during an afternoon hyperinsulinemic-hyperglycemic (HIHG) clamp. Our current aim was to determine if the duration or pattern of morning hyperinsulinemia is important for the afternoon response to a HIHG clamp. To determine this, the same total amount of insulin was administered either over 2 h in the first (Ins2h-A) or second (Ins2h-B) half of the morning or over the entire 4 h (Ins4h) of the morning. In the 4-h afternoon period, all three groups had 4x-basal insulin, 2x-basal glycemia, and portal glucose infusion to expose the liver to the primary postprandial regulators of hepatic glucose metabolism. During the afternoon clamp, there was a marked increase in HGU and hepatic glycogen synthesis in the Ins4h group compared with the Ins2h-A and Ins2h-B groups, despite matched hepatic glucose loads and total insulin infusion rates. Thus, the longer duration (Ins4h) of lower hyperinsulinemia in the morning seems to be the key to much greater liver glucose uptake during the afternoon clamp.NEW & NOTEWORTHY Morning insulin exposure primes the liver for increased hepatic glucose uptake and glycogen storage during a subsequent hyperinsulinemic-hyperglycemic clamp. This study addressed whether the pattern and/or duration of insulin delivery in the morning influences insulin's ensuing priming effect. We found that despite receiving equal total doses of insulin in the morning, a prolonged, lower rate of morning insulin delivery improved afternoon liver glucose metabolism more effectively than a shorter, higher rate of delivery.

The relationship between community food environment around schools and student meal participation: the role of school CEP participation status.

BACKGROUND: Despite the many benefits of school meals, not all students participate. One reason students may not participate in school meals is because they instead purchase breakfast or lunch from food outlets located around schools that mostly carry unhealthy items. This study examined whether school participation in the Community Eligibility Provision (CEP), which allows qualifying schools to serve free meals to all students, moderated the association between the community food environment around schools and student meal participation. METHODS: This study employed a longitudinal repeated-measures design using school-level data collected between 2014 and 2020 within four low-income school districts (n = 126 schools) in the US. We obtained meal participation data from state records and created a measure characterizing the community food environment within 0.25 miles of schools (characterized as low-density of unhealthy food outlets vs. high-density of unhealthy food outlets) through a latent class analysis. Regression analysis estimated associations between community food environments, CEP participation, and participation rates in school breakfast and school lunch, assessed in separate models. RESULTS: While no moderating effect of school CEP status was observed for breakfast or lunch participation, school breakfast participation was predicted to be 4% lower in high-density food environments than in low-density environments (P-value = .049) among non-CEP schools, and there was no difference in participation by the community food environment among CEP-participating schools. Differences in breakfast participation by the community food environment among non-CEP schools were mostly attributable to middle/high schools, with participation predicted to be 10% lower in high-density environments than in low-density environments among non-CEP middle/high schools (P-value < .001), whereas such a difference in participation was not observed among non-CEP elementary schools. CONCLUSIONS: Negative associations between food environment around schools and school breakfast participation were observed only among middle and high schools not participating in CEP, suggesting that policy actions to increase access to free school meals may benefit students, particularly older children and adolescents.

A time-course analysis of Aspergillus terreus secretomes reveals the importance of pectin-degrading enzymes to increase the digestibility of soybean meal.

Considering an ever-growing global population, which hit 8 billion people in the fall of 2022, it is essential to find solutions to avoid croplands competition between human food and animal feed. Agricultural co-products such as soybean meals have become important components of the circular economy thanks to their use in animal feed. Their implementation was made possible by the addition of exogenous enzymes in the diet of monogastric animals, especially fungal carbohydrate-active enzymes (CAZymes). Here, we describe a time-course production and analysis of Aspergillus terreus secretomes for the identification of CAZymes able to enhance the digestibility of soybean meals. Functional assays revealed that the release of nutrients and the degradation of pectins in soybean meals can be tightly interconnected. Using a comparative proteomics approach, we identified several fungal pectin-degrading enzymes leading to increased assimilable nutrients in the soluble fraction of soybean meals. Our results reinforce the importance of deconstructing pectic polysaccharides in feedstuffs and contribute to sharpen our understanding of the fungal enzymatic interplays involved in pectin hydrolysis.IMPORTANCEIn the present study, we developed a strategy to identify the key fungal enzymatic activities involved in the improvement of soybean meal (SBM) digestibility. Our data unravel the importance of pectin degradation for the release of nutrients from SBM and provide some insights regarding the degradation of rhamnogalacturonan-I (RG-I) by ascomycetes. Indeed, the hydrolysis of pectins and RG-I by human microbiota is well documented in the literature, but our knowledge of the fungal CAZymes at play for the degradation of soybean pectins remains hitherto underexplored. Due to its wide use in animal feed, improving the digestibility of SBM by enzymatic treatments is a current challenge for feed additive suppliers. Since non-starch polysaccharides and pectins have often been reported for their anti-nutritional role in SBM, we believe this study will provide new avenues toward the improvement of enzymatic cocktails for animal nutrition and health.

Hepatic insulin resistance and muscle insulin resistance are characterized by distinct postprandial plasma metabolite profiles: a cross-sectional study.

BACKGROUND: Tissue-specific insulin resistance (IR) predominantly in muscle (muscle IR) or liver (liver IR) has previously been linked to distinct fasting metabolite profiles, but postprandial metabolite profiles have not been investigated in tissue-specific IR yet. Given the importance of postprandial metabolic impairments in the pathophysiology of cardiometabolic diseases, we compared postprandial plasma metabolite profiles in response to a high-fat mixed meal between individuals with predominant muscle IR or liver IR. METHODS: This cross-sectional study included data from 214 women and men with BMI 25-40 kg/m2, aged 40-75 years, and with predominant muscle IR or liver IR. Tissue-specific IR was assessed using the muscle insulin sensitivity index (MISI) and hepatic insulin resistance index (HIRI), which were calculated from the glucose and insulin responses during a 7-point oral glucose tolerance test. Plasma samples were collected before (T = 0) and after (T = 30, 60, 120, 240 min) consumption of a high-fat mixed meal and 247 metabolite measures, including lipoproteins, cholesterol, triacylglycerol (TAG), ketone bodies, and amino acids, were quantified using nuclear magnetic resonance spectroscopy. Differences in postprandial plasma metabolite iAUCs between muscle and liver IR were tested using ANCOVA with adjustment for age, sex, center, BMI, and waist-to-hip ratio. P-values were adjusted for a false discovery rate (FDR) of 0.05 using the Benjamini-Hochberg method. RESULTS: Sixty-eight postprandial metabolite iAUCs were significantly different between liver and muscle IR. Liver IR was characterized by greater plasma iAUCs of large VLDL (p = 0.004), very large VLDL (p = 0.002), and medium-sized LDL particles (p = 0.026), and by greater iAUCs of TAG in small VLDL (p = 0.025), large VLDL (p = 0.003), very large VLDL (p = 0.002), all LDL subclasses (all p < 0.05), and small HDL particles (p = 0.011), compared to muscle IR. In liver IR, the postprandial plasma fatty acid (FA) profile consisted of a higher percentage of saturated FA (p = 0.013), and a lower percentage of polyunsaturated FA (p = 0.008), compared to muscle IR. CONCLUSION: People with muscle IR or liver IR have distinct postprandial plasma metabolite profiles, with more unfavorable postprandial metabolite responses in those with liver IR compared to muscle IR.

Circulating total and H-specific GDF15 levels are elevated in subjects with MASLD but not in hyperlipidemic but otherwise metabolically healthy subjects with obesity.

BACKGROUND: Growth differentiation factor 15 (GDF15) is a mitokine, the role of which, total or H-specific, in modulating energy metabolism and homeostasis in obesity-related diseases, such as metabolic dysfunction associated steatotic liver disease (MASLD), has not been fully elucidated in adult humans. We aimed to investigate the fasting and stimulated levels of GDF15, total and H-specific, glucose-dependent insulinotropic polypeptide (GIP) and C-peptide, in two physiology interventional studies: one focusing on obesity, and the other on MASLD. METHODS: Study 1 investigated individuals with normal weight or with obesity, undergoing a 3-h mixed meal test (MMT); and study 2, examined adults with MASLD and controls undergoing a 120-min oral glucose tolerance test (OGTT). Exploratory correlations of total and H-specific GDF15 with clinical, hormonal and metabolomic/lipidomic parameters were also performed. RESULTS: In study 1, 15 individuals were included per weight group. Fasting and postprandial total and H-specific GDF15 were similar between groups, whereas GIP was markedly higher in leaner individuals and was upregulated following a MMT. Baseline and postprandial C-peptide were markedly elevated in people with obesity compared with lean subjects. GIP was higher in leaner individuals and was upregulated after a MMT, while C-peptide and its overall AUC after a MMT was markedly elevated in people with obesity compared with lean subjects. In study 2, 27 individuals were evaluated. Fasting total GDF15 was similar, but postprandial total GDF15 levels were significantly higher in MASLD patients compared to controls. GIP and C-peptide remained unaffected. The postprandial course of GDF15 was clustered among those of triglycerides and molecules of the alanine cycle, was robustly elevated under MASLD, and constituted the most notable differentiating molecule between healthy and MASLD status. We also present robust positive correlations of the incremental area under the curve of total and H-specific GDF15 with a plethora of lipid subspecies, which remained significant after adjusting for confounders. CONCLUSION: Serum GDF15 levels do not differ in relation to weight status in hyperlipidemic but otherwise metabolically healthy individuals. In contrast, GDF15 levels are significantly increased in MASLD patients at baseline and they remain significantly higher compared to healthy participants during OGTT, pointing to a role for GDF15 as a mitokine with important roles in the pathophysiology and possibly therapeutics of MASLD. Trial registration ClinicalTrials.gov NCT03986684, NCT04430946.

Chrononutrition in type 2 diabetes mellitus and obesity: A narrative review.

Chrononutrition is a nutritional regimen that follows our biological clock, marked by the changes in metabolism that occur during the day. This regimen includes the distribution of energy, the regularity and frequency of meals, and the importance of these factors for metabolic health. A growing body of animal and human evidence indicates that the timing of food intake throughout the day can have a significant and beneficial impact on the metabolic health and well-being of individuals. In particular, both the timing and frequency of meals have been associated with obesity, type 2 diabetes mellitus (T2DM), cardiovascular disease, and other chronic conditions. Today's busy lifestyle makes many people skip breakfast and eat late at night. Eating late at night has been shown to cause a circadian misalignment, with the latter having a negative impact on weight control and glucose metabolism. Additionally, some studies have found a relatively strong association between skipping breakfast and insulin resistance, and T2DM. Against the backdrop of escalating obesity and T2DM rates, coupled with the recognized influence of food timing on disease evolution and control, this review aimed to synthesize insights from epidemiological and intervention studies of the interplay of timing of food intake and macronutrient consumption, reporting their impact on obesity and T2DM.

Meal replacements on obesity and leptin: a systematic review and meta-analysis.

The global prevalence of obesity and overweight is a significant concern in the field of public health. Numerous interventional studies have been conducted to assess the possible meal replacements (MRs) effect on anthropometric indicators and indices and laboratory test that reflect obesity. However, there are no comprehensive results in this field. The study aim was to understand the possible effects of MRs on body weight, body mass index (BMI), fat mass, waist circumferences (WC), and leptin levels. A systematic search was conducted in five electronic databases in order to find randomized clinical trials (RCTs) that examined the possible MRs effect on obesity. Analyses were performed in R software, version 4.2.1. The random-effects model analysis was used to provide pooled mean difference and 95% confidence intervals (95% CI). Seventy studies were included. Body weight (WMD: -3.35 kg, 95% CI: -4.28 to -2.42), BMI (WMD: -1.12 kg/m2, 95% CI: -1.51 to -0.72), fat mass (WMD: -2.77 kg, 95% CI: -3.59 to -1.6), WC (WMD: -2.82 cm, 95% CI: -3.51 to -2.12) were significantly reduced after MRs compared to control. No significant effect was observed on leptin (WMD: -3.37 ng/ml, 95% CI: -8.23 to 1.49). Subgroup analyses indicated that impact of total MRs on anthropometric factors was greater in comparison to partial MRs. Considering other lifestyle factors, MRs can lead to anthropometric indicators and indices reduction.

The Effect of Meal Glycemic Index and Meal Frequency on Glycemic Control and Variability in Female Nurses Working Night Shifts: A Two-Arm Randomized Cross-Over Trial.

BACKGROUND: Night shift workers are exposed to circadian disruption, which contributes to impaired glucose tolerance. Although fasting during the night shift improves glucose homeostasis, adhering to this dietary strategy may be challenging. OBJECTIVES: This study evaluated the effect of fasting compared with the consumption of meals with different combinations of glycemic index (GI, low or high) and frequency (1 or 3 times) during the night shift on continuous glucose monitoring metrics. METHODS: A 2-arm randomized cross-over trial was conducted on female nurses working night shifts. In each of those arms, the participants were either provided with no meal (fasted), low GI, or high-GI meal during the night shift with a meal frequency according to which arm they were randomly allocated to, either 1-MEAL or 3-MEAL. Outcome variables were glycemic control and variability (GC and GV) metrics during the night shift (21:30-7:00), in the morning after the night shift (07:00-13:00), and in the 24 h period (18:00-18:00). RESULTS: Compared to no meal, the consumption of 1 high-GI meal increased all GV metrics not only during the night shifts but also in the morning, for instance, as observed in the coefficient of variation (ß = 0.03 mmol/L; 95% CI: 0.01, 0.05), and GV percentage (ß = 4.13; 95% CI: 2.07, 6.18). The consumption of 1 or 3 low GI meals did not raise GC or GV metrics except for continuous overall net glycemic action during the night shifts after consuming 3 low GI meals. When controlling for GI, night shift meal frequency did not affect any metrics in any timeframe. CONCLUSIONS: High meal GI but not higher meal frequency during the night shift increased GC and GV in female night shift workers. Results for 1 low-GI meal during the night shift were not different from a glucose profile after no meal. This trial was registered at trialsearch.who.int as NL8715.

Meals Containing Equivalent Total Protein from Foods Providing Complete, Complementary, or Incomplete Essential Amino Acid Profiles do not Differentially Affect 24-h Skeletal Muscle Protein Synthesis in Healthy, Middle-Aged Women.

BACKGROUND: Dietary protein quality can be assessed by skeletal muscle protein synthesis (MPS) stimulation. Limited knowledge exists on how consuming isonitrogenous meals with varied protein qualities affects postprandial and 24-h MPS. OBJECTIVES: We assessed the effects of protein quality and complementary proteins on MPS. We hypothesized that meals containing a moderate amount of high-quality, complete protein would stimulate postprandial and 24-h MPS. Meals containing two complementary, plant-based incomplete proteins would stimulate MPS less, and meals containing plant-based incomplete proteins at each meal, but complementary over 24 h would not stimulate MPS. METHODS: This quasi-experimental study included a randomized, crossover design to assess protein quality and a nonrandomized low-protein control. We measured postprandial and 24-h MPS responses of healthy middle-aged women (n = 9, age 56 ± 4 y), to 3 dietary conditions: isonitrogenous meals containing 23 g protein/meal from 1) complete protein (lean beef), 2) 2 incomplete, but complementary protein sources (navy/black beans and whole wheat bread), and 3) single incomplete protein sources (black beans or whole wheat bread at 1 meal), but providing a complete amino acid profile over 24 h. In the low-protein group women (n = 8, 54 ± 5 y) consumed a single breakfast meal containing 5 g of protein. Venous blood and vastus lateralis samples were obtained during primed, constant infusions of L-[ring-13C6]phenylalanine to measure mixed muscle fractional synthetic rates (FSR). RESULTS: Meals containing complete, complementary, or incomplete proteins did not differentially influence FSR responses after breakfast (P = 0.90) or 24 h (P = 0.38). At breakfast, the complete (P = 0.030) and complementary (P = 0.031) protein meals, but not the incomplete protein meal (P = 0.38), had greater FSR responses compared with the low-protein control meal. CONCLUSIONS: Isonitrogenous meals containing a moderate serving of total protein from foods providing complete, complementary, or incomplete essential amino acid profiles do not differentially stimulate muscle protein synthesis after a meal and daily. TRIAL REGISTRATION NUMBER: This clinical trial was registered at clinicaltrials.gov as NCT03816579. URL: https://www. CLINICALTRIALS: gov/ct2/show/NCT03816579?term=NCT03816579&draw=2&rank=1.

Acute nicotine intake increases feeding behavior through decreasing glucagon signaling in dependent male and female rats.

Chronic use of nicotine is known to dysregulate metabolic signaling through altering circulating levels of feeding-related hormones, contributing to the onset of disorders like type 2 diabetes. However, little is known about the acute effects of nicotine on hormonal signaling. We previously identified an acute increase in food intake following acute nicotine, and we sought to determine whether this behavior was due to a change in hormone levels. We first identified that acute nicotine injection produces an increase in feeding behavior in dependent rats, but not nondependent rats. We confirmed that chronic nicotine use increases circulating levels of insulin, leptin, and ghrelin, and these correlate with rats' body weight and food intake. Acute nicotine injection in dependent animals decreased circulating GLP-1 and glucagon levels, and administration of glucagon prior to acute nicotine injection prevented the acute increase in feeding behavior. Thus, acute nicotine injection increases feeding behavior in dependent rats by decreasing glucagon signaling.

Livestock keeping, mosquitoes and community viewpoints: a mixed methods assessment of relationships between livestock management, malaria vector biting risk and community perspectives in rural Tanzania.

BACKGROUND: Livestock keeping is one of the potential factors related to malaria transmission. To date, the impact of livestock keeping on malaria transmission remains inconclusive, as some studies suggest a zooprophylactic effect while others indicate a zoopotentiation effect. This study assessed the impact of livestock management on malaria transmission risks in rural Tanzania. Additionally, the study explored the knowledge and perceptions of residents about the relationships between livestock keeping and malaria transmission risks in a selected village. METHODS: In a longitudinal entomological study in Minepa village, South Eastern Tanzania, 40 households were randomly selected (20 with livestock, 20 without). Weekly mosquito collection was performed from January to April 2023. Indoor and outdoor collections used CDC-Light traps, Prokopack aspirators, human-baited double-net traps, and resting buckets. A subsample of mosquitoes was analysed using PCR and ELISA for mosquito species identification and blood meal detection. Livestock's impact on mosquito density was assessed using negative binomial GLMMs. Additionally, in-depth interviews explored community knowledge and perceptions of the relationship between livestock keeping and malaria transmission risks. RESULTS: A total of 48,677 female Anopheles mosquitoes were collected. Out of these, 89% were Anopheles gambiae sensu lato (s.l.) while other species were Anopheles funestus s.l., Anopheles pharoensis, Anopheles coustani, and Anopheles squamosus. The findings revealed a statistically significant increase in the overall number of An. gambiae s.l. outdoors (RR = 1.181, 95%CI 1.050-1.862, p = 0.043). Also, there was an increase of the mean number of An. funestus s.l. mosquitoes collected in households with livestock indoors (RR = 2.866, 95%CI: 1.471-5.582, p = 0.002) and outdoors (RR = 1.579,95%CI 1.080-2.865, p = 0.023). The human blood index of Anopheles arabiensis mosquitoes from houses with livestock was less than those without livestock (OR = 0.149, 95%CI 0.110-0.178, p < 0.001). The majority of participants in the in-depth interviews reported a perceived high density of mosquitoes in houses with livestock compared to houses without livestock. CONCLUSION: Despite the potential for zooprophylaxis, this study indicates a higher malaria transmission risk in livestock-keeping communities. It is crucial to prioritize and implement targeted interventions to control vector populations within these communities. Furthermore, it is important to enhance community education and awareness regarding covariates such as livestock that influence malaria transmission.

Sex-specific chrono-nutritional patterns and association with body weight in a general population in Spain (GCAT study).

BACKGROUND: Altered meal timing patterns can disrupt the circadian system and affect metabolism. Our aim was to describe sex-specific chrono-nutritional patterns, assess their association with body mass index (BMI) and investigate the role of sleep in this relationship. METHODS: We used the 2018 questionnaire data from the population-based Genomes for Life (GCAT) (n = 7074) cohort of adults aged 40-65 in Catalonia, Spain, for cross-sectional analysis and its follow-up questionnaire data in 2023 (n = 3128) for longitudinal analysis. We conducted multivariate linear regressions to explore the association between mutually adjusted meal-timing variables (time of first meal, number of eating occasions, nighttime fasting duration) and BMI, accounting for sleep duration and quality, and additional relevant confounders including adherence to a Mediterranean diet. Finally, cluster analysis was performed to identify chrono-nutritional patterns, separately for men and women, and sociodemographic and lifestyle characteristics were compared across clusters and analyzed for associations with BMI. RESULTS: In the cross-sectional analysis, a later time of first meal (ß 1 h increase = 0.32, 95% CI 0.18, 0.47) and more eating occasions (only in women, ß 1 more eating occasion = 0.25, 95% CI 0.00, 0.51) were associated with a higher BMI, while longer nighttime fasting duration with a lower BMI (ß 1 h increase=-0.27, 95% CI -0.41, -0.13). These associations were particularly evident in premenopausal women. Longitudinal analyses corroborated the associations with time of first meal and nighttime fasting duration, particularly in men. Finally, we obtained 3 sex-specific clusters, that mostly differed in number of eating occasions and time of first meal. Clusters defined by a late first meal displayed lower education and higher unemployment in men, as well as higher BMI for both sexes. A clear "breakfast skipping" pattern was identified only in the smallest cluster in men. CONCLUSIONS: In a population-based cohort of adults in Catalonia, we found that a later time of first meal was associated with higher BMI, while longer nighttime fasting duration associated with a lower BMI, both in cross-sectional and longitudinal analyses.

Association of the timing of evening eating with BMI Z-score and waist-to-height ratio among preschool-aged children in Finland.

Later timing of eating has been associated with higher adiposity among adults and children in several studies, but not all. Moreover, studies in younger children are scarce. Hence, this study investigated the associations of the timing of evening eating with BMI Z-score and waist-to-height ratio (WHtR), and whether these associations were moderated by chronotype among 627 preschoolers (3-6-year-olds) from the cross-sectional DAGIS survey in Finland. Food intake was measured with 3-d food records, and sleep was measured with hip-worn actigraphy. Three variables were formed to describe the timing of evening eating: (1) clock time of the last eating occasion (EO); (2) time between the last EO and sleep onset; and (3) percentage of total daily energy intake (%TDEI) consumed 2 h before sleep onset or later. Chronotype was assessed as a sleep debt-corrected midpoint of sleep on the weekend (actigraphy data). The data were analysed with adjusted linear mixed effects models. After adjusting for several confounders, the last EO occurring closer to sleep onset (estimate = -0·006, 95 % CI (-0·010, -0·001)) and higher %TDEI consumed before sleep onset (estimate = 0·0004, 95 % CI (0·00003, 0·0007)) were associated with higher WHtR. No associations with BMI Z-score were found after adjustments. Clock time of the last EO was not significantly associated with the outcomes, and no interactions with chronotype emerged. The results highlight the importance of studying the timing of eating relative to sleep timing instead of only as clock time.

Consistent effect of eating rate on food and energy intake across twenty-four ad libitum meals.

Foods consumed at lower eating rates (ER) lead to reductions in energy intake. Previous research has shown that texture-based differences in eating rateER can reduce meal size. The effect size and consistency of these effects across a wide range of composite and complex meals differing considerably in texture and varying in meal occasion have not been reported. We determined how consistently texture-based differences in ER can influence food and energy intake across a wide variety of meals. In a crossover design, healthy participants consumed twelve breakfast and twelve lunch meals that differed in texture to produce a fast or slow ER. A breakfast group (n = 15) and lunch group (n = 15) completed twelve ad libitum meal sessions each (six 'fast' and six 'slow' meals), where intake was measured and behavioural video annotation was used to characterise eating behaviour. Liking did not differ significantly between fast and slow breakfasts (P = 0·44) or lunches (P = 0·76). The slow meals were consumed on average 39 % ± 9 % (breakfast) and 45 % ± 7 % (lunch) slower than the fast meals (both P < 0·001). Participants consumed on average 22 % ± 5 % less food (84 g) and 13 % ± 6 % less energy (71 kcal) from slow compared with fast meals (mean ± SE; P < 0·001). Consuming meals with a slower ER led to a reduction in food intake, where an average decrease of 20 % in ER produced an 11 % ± 1 % decrease in food intake (mean ± SE). These findings add to the growing body of evidence showing that ER can be manipulated using food texture and that this has aits consistent effect on food and energy intake across a wide variety of Hedonically equivalent meals.

Rosmarinic acid mitigates intestinal inflammation and oxidative stress in bullfrogs (Lithobates catesbeiana) fed high soybean meal diets.

High proportions of soybean meal in aquafeed have been confirmed to induce various intestinal pathologies. This study aims to investigate the regulatory effects of rosmarinic acid (RA), an antioxidant with anti-inflammatory and antimicrobial properties, when added to high soybean meal feeds in different doses, (0, 0.5, 1, and 4 g/kg). During the 56-day feeding trial, results indicated that, compared to the control group without RA (0 g/kg), the 1 g/kg and 4 g/kg RA groups increased bullfrog survival rates and total weight gain while reducing feed coefficient. Additionally, these doses markedly suppressed the expression of key intestinal inflammatory markers (tlr5, myd88, tnfα, il1ß, cxcl8, cxcl12) and the activity and content of intestinal antioxidants (CAT, MDA, GSH, GPX). Concurrently, RA significantly downregulated the transcription levels of antioxidant-related genes (cat, gpx5, cyba, cybb, mgst, gclc, gsta, gstp), suggesting RA's potential to alleviate intestinal inflammation and oxidative stress induced by high soybean meal and to help downregulate and restore normal expression of antioxidant enzyme genes. However, the 0.5 g/kg RA group did not show a significant improvement in survival rates; instead, it upregulated the transcription of some antioxidant genes (cat, gpx5, cyba, cybb), revealing the complexity and dose-dependency of RA's antioxidant action. Furthermore, RA supplementation significantly reshaped the intestinal microbial community structure and relative abundance in bullfrogs, particularly affecting the genera Hafnia, Phascolarctobacterium, and Lactococcus. Notably, high doses of RA (1 g/kg, 4 g/kg) were able to downregulate pathways associated with the enrichment of gut microbiota in diseases such as Parkinson's, Staphylococcus aureus infection, and Systemic lupus erythematosus, suggesting its potential in anti-inflammatory action and health maintenance to prevent potential diseases.