A high nutrient dense diet alters hypothalamic gene expressions to influence energy intake in pigs born with low birth weight.
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ABSTRACT:
SUBMITTER: Liu J
PROVIDER: S-EPMC5882958 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:Feeding behavior regulation is a complex process, which depends on the central integration of different signals, such as glucose, leptin, and ghrelin. Recent studies have shown that glial cells known as tanycytes that border the basal third ventricle (3V) detect glucose and then use glucose-derived signaling to inform energy status to arcuate nucleus (ARC) neurons to regulate feeding behavior. Monocarboxylate transporters (MCT) 1 and MCT4 are localized in the cellular processes of tanycytes, which could facilitate monocarboxylate release to orexigenic and anorexigenic neurons. We hypothesize that MCT1 and MCT4 inhibitions could alter the metabolic communication between tanycytes and ARC neurons, affecting feeding behavior. We have previously shown that MCT1 knockdown rats eat more and exhibit altered satiety parameters. Here, we generate MCT4 knockdown rats and MCT1-MCT4 double knockdown rats using adenovirus-mediated transduction of a shRNA into the 3V. Feeding behavior was evaluated in MCT4 and double knockdown animals, and neuropeptide expression in response to intracerebroventricular glucose administration was measured. MCT4 inhibition produced a decrease in food intake, contrary to double knockdown. MCT4 inhibition was accompanied by a decrease in eating rate and mean meal size and an increase in mean meal duration, parameters that are not changed in the double knockdown animals with exception of eating rate. Finally, we observed a loss in glucose regulation of orexigenic neuropeptides and abnormal expression of anorexigenic neuropeptides in response to fasting when these transporters are inhibited. Taken together, these results indicate that MCT1 and MCT4 expressions in tanycytes play a role in feeding behavior regulation.
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Project description:Early nutrition is one of the most modifiable factors influencing postnatal growth. Optimal nutrient intakes for very preterm infants remain unknown, and poor postnatal growth is common in this population. The aim of this study was to assess nutrient intake during the first 4 weeks of life with early progressive enteral feeding and its impact on the in-hospital growth of very low-birth-weight (VLBW) infants. In total, 120 infants with birth weights below 1500 g and gestational ages below 35 weeks were included in the study. Nutrient intakes were assessed daily for the first 28 days. Growth was measured weekly until discharge. Median time of parenteral nutrition support was 6 days. Target enteral nutrient and energy intake were reached at day 10 of life, and remained stable until day 28, with slowly declining protein intake. Median z-scores at discharge were -0.73, -0.49, and -0.31 for weight, length, and head circumference, respectively. Extrauterine growth restriction was observed in 30.3% of the whole cohort. Protein, carbohydrates, and energy intakes correlated positively with weight gain and head circumference growth. Early progressive enteral feeding with human milk is well tolerated in VLBW infants. Target enteral nutrient intake may be reached early and improve in-hospital growth.
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Project description:Optimal nutrient intake ensuring better neurodevelopment for very low birth weight (VLBW) infants remains unknown. The aim of this study was to assess the relationship between early (first 28 days) nutritional intake, first year growth, and neurodevelopment. In total, 120 VLBW infants were included into the study. A group of 95 infants completed follow-up to 12 months of corrected gestational age (CGA). Nutrient intake was assessed, and weight, length, and head circumference (HC) were measured weekly until discharge and at 3, 6, 9, and 12 months of CGA. Neurodevelopment was assessed at 12 months of CGA. Two groups-extremely preterm (EP) and very/moderately preterm (VP)-were compared. Growth before discharge was slower in the EP group than the VP group. At 12 months, there was no difference in anthropometric characteristics or neurodevelopmental scores between the groups. Higher carbohydrate intake during the first 28 days was the single significant predictor for better cognitive scores only in the EP group (βs = 0.60, p = 0.017). Other nutrients and growth before discharge were not significant for cognitive and motor scores in either group in multivariable models, whereas post-discharge HC growth was associated with both cognitive and motor scores in the VP group. Monitoring intake of all nutrients and both pre-discharge and post-discharge growth is essential for gaining knowledge about individualized nutrition for optimal neurodevelopment.
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Project description:The hypothalamus has a vital role in controlling food intake and energy homeostasis; its activity is modulated by neuropeptides and endocrine factors. Mesencephalic astrocyte-derived neurotrophic factor (MANF) is a neurotrophic factor that is also localized in the endoplasmic reticulum (ER) in neurons. Here we show that MANF is highly enriched in distinct nuclei of the mouse hypothalamus, and that MANF expression in the hypothalamus is upregulated in response to fasting. Increasing or decreasing hypothalamic MANF protein levels causes hyperphagia or hypophagia, respectively. Moreover, MANF triggers hypothalamic insulin resistance by enhancing the ER localization and activity of PIP4k2b, a kinase known to regulate insulin signaling. Our findings indicate that MANF influences food intake and body weight by modulating hypothalamic insulin signaling.MANF is a neurotrophic factor that is secreted but also mediates the unfolded protein response acting intracellularly. Here, the authors show that MANF expression in the brain is influenced by nutritional cues, and hypothalamic MANF influences food intake and systemic energy homeostasis.
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Project description:Being born at extremely low birth weight (ELBW; ≤1,000 g) is associated with enduring visual impairments. We tested for long-term, higher order visual processing problems in the oldest known prospectively followed cohort of ELBW survivors. Configural processing (spacing among features of an object) was examined in 62 adults born at ELBW (Mage = 31.9 years) and 82 adults born at normal birth weight (NBW; ≥2,500 g: Mage = 32.5 years). Pairs of human faces, monkey faces, or houses were presented in a delayed match-to-sample task, where non-matching stimuli differed only in the spacing of their features. Discrimination accuracy for each stimulus type was compared between birth weight groups, adjusting for neurosensory impairment, visual acuity, binocular fusion ability, IQ, and sex. Both groups were better able to discriminate human faces than monkey faces (p < .001). However, the ELBW group discriminated between human faces (p < .001), between monkey faces (p < .001), and to some degree, between houses (p < .06), more poorly than NBW control participants, suggesting a general deficit in perceptual processing. Human face discrimination was related to performance IQ (PIQ) across groups, but especially among ELBW survivors. Coding (a PIQ subtest) also predicted human face discrimination in ELBW survivors, consistent with previously reported links between visuo-perceptive difficulties and regional slowing of cortical activity in individuals born preterm. Correlations with Coding suggested ELBW survivors may have used a feature-matching approach to processing human faces. Future studies could examine brain-based anatomical and functional evidence for altered face processing, as well as the social and memory consequences of face-processing deficits in ELBW survivors.
| S-EPMC6983349 | biostudies-literature
Project description:Children born very low birth weight (VLBW, <1,500 g) are at high risk for cognitive and academic difficulties later in life. Although early nutrition (e.g., breastfeeding) is positively correlated with IQ in children born VLBW, the association between dietary intake in childhood and cognitive performance is unknown. Thus, our study is the first to investigate the relationship between diet quality, as measured by the Healthy Eating Index-2010 (HEI-2010) and cognitive performance in a Canadian cohort of 5-year-old children born VLBW (n = 158; 47% female). Diet quality was measured using two 24-h diet recalls obtained from parents and cognitive performance was assessed using the Wechsler Preschool and Primary Scale of Intelligence-IV (WPPSI-IV). To account for additional sociodemographic factors that could influence neurodevelopment, linear regression analyses were adjusted for sex, household income above/below the poverty line, maternal education, birth weight and breastfeeding duration. Mean ± SD HEI-2010 score was 58.2 ± 12.4, with most children (67%) having diets in "need of improvement" (scores 51-80). HEI-2010 scores were not significantly associated with IQ or any other WPPSI-IV composite score. Significant predictors of IQ in our model were birth weight, sex, and maternal education. Our findings emphasize the important role of maternal education and other sociodemographic factors on neurodevelopment in children born VLBW. Further, despite not finding any significant association between HEI-2010 scores and IQ, our results highlight the need to improve diet quality in young children born VLBW. Further research is needed to confirm the impact of diet quality on cognitive performance in this vulnerable population.
| S-EPMC9343771 | biostudies-literature
Project description:In commercial pig farming, an increasing number of low birth weight (LBW) piglets are born, due to selection for large litter sizes. While LBW piglets have a higher risk of pre-weaning mortality, a considerable number of these piglets survive to slaughter age. In humans, LBW is a risk factor for long-term cognitive impairments. In pigs, studies examining the post-weaning effects of LBW on cognition have reported contradictory results. Therefore, the current study aimed to assess the effects of LBW on cognitive development in pigs using an improved study design, by (1) testing a larger sample size than previous studies, (2) assessing acute and chronic stress responses to account for a potential altered stress response in LBW pigs, and (3) testing both female and male pigs to account for potential confounding effects of sex. Learning and memory of 20 LBW pigs and 20 normal birth weight (NBW) pigs, both groups consisting of 10 females and 10 males, were compared using a spatial holeboard task. In this task, pigs had to learn and remember the locations of hidden food rewards. After a pig had successfully acquired the task, it was presented with two successive reversal phases during which it was presented with a new configuration of reward locations. The holeboard allows for simultaneous assessment of working and reference memory, as well as measures of motivation, exploration, and behavioral flexibility. Mixed model ANOVAs revealed a transiently impaired reference memory performance of LBW pigs, implying they had more difficulty learning their reward configuration in the holeboard. Also, LBW piglets showed increased pre-weaning hair cortisol concentrations compared to their NBW siblings. No other effects of LBW were found. Sex had no direct or interaction effects on any measures of holeboard performance or stress. It is possible that the enriched housing conditions applied during our study had an ameliorating effect on our pigs' cognitive development. Overall, our results suggest LBW has a negative effect on post-weaning cognitive performance in pigs. This could have welfare consequences as cognitive skills are required for pigs to learn how to correctly respond to their environment.
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Project description:Infants born at very low birth weight (<1500 g) are vulnerable to nutritional deficits during their first postnatal month, which are associated with poor neurodevelopmental outcomes. Despite this knowledge, the impact of early postnatal nutrition on white matter microstructure in children born with very low birth weight has not been investigated. In this prospective cohort study, we employed a whole-brain approach to investigate associations between precise estimates of nutrient intake within the first postnatal month with white matter microstructure at 5 years of age. Detailed information about breastmilk, macronutrient and energy intakes during this period were prospectively recorded for all participants. Multi-shell diffusion and T1-weighted MRIs were acquired in 41 children (21 males; mean scan age: 5.75 ± 0.22 years; mean birth weight: 1028.6 ± 256.8 g). The diffusion tensor imaging and neurite orientation dispersion and density imaging models were used to obtain maps of fractional anisotropy, radial diffusivity, orientation dispersion and neurite density indices. Tract-based spatial statistics was used to test associations between metrics of white matter microstructure with breastmilk, macronutrient (protein, lipids and carbohydrate) and energy intake. Associations between white matter microstructure and cognitive outcomes were also examined. Compared to children who did not meet enteral feeding recommendations, those who achieved enteral protein, lipid and energy recommendations during the first postnatal month showed improved white matter maturation at 5 years. Among the macronutrients, greater protein intake contributed most to the beneficial effect of nutrition, showing widespread increases in fractional anisotropy and reductions in radial diffusivity. No significant associations were found between white matter metrics with breastmilk or carbohydrate intake. Voxel-wise analyses with cognitive outcomes revealed significant associations between higher fractional anisotropy and neurite density index with higher processing speed scores. Lower radial diffusivity and orientation dispersion index were also associated with improved processing speed. Our findings support the long-term impacts of early nutrition on white matter microstructure, which in turn is related to cognitive outcomes. These results provide strong support for early postnatal nutritional intervention as a promising strategy to improve long-term cognitive outcomes of infants born at very low birth weight.
| S-EPMC8100003 | biostudies-literature
Project description:BackgroundVery low birth weight (VLBW) infants are at risk for disrupted white matter maturation, yet little is known about the contributing factors, particularly at preschool-age when cognitive difficulties begin to emerge. We examined white matter microstructure in five-year-old VLBW and full-term (FT) children, and its association with cognitive outcomes and birth weight.MethodsMulti-shell diffusion and MR images were obtained for 41 VLBW (mean birth weight: 1028.6 ± 256.8 g) and 26 FT (3295.4 ± 493.9 g) children. Fractional anisotropy (FA), radial diffusivity (RD), neurite orientation dispersion index (ODI) and density index (NDI) were estimated using diffusion tensor and neurite orientation dispersion and density imaging models. Between-group analyses used a general linear model with group and sex as explanatory variables. Within-group associations between white matter microstructure, cognitive outcomes and birth weight were also investigated.ResultsVLBW compared to FT children showed lower FA and NDI across widespread white matter regions. Smaller clusters of atypical ODI were also found in VLBW children. Within-group analyses in FT children revealed that lower RD and higher NDI were associated with vocabulary acquisition and working memory. In VLBW children, higher FA and NDI, and lower RD and ODI, were associated with improved processing speed. In both groups, FA was positively associated with birth weight.ConclusionsOur findings demonstrate white matter alterations in young VLBW children, including widespread reductions in axon density that may reflect sustained myelination disruptions. The associations with cognitive outcomes may also highlight which of the VLBW children are at higher risk for later cognitive difficulties.
| S-EPMC8496319 | biostudies-literature
Project description:Objectives To explore associations between race, nativity, and low birth weight (LBW) among Latina and non-Latina women, with special attention to the Black Latina subgroup. Methods Using US natality data from 2011 to 2013, we designed a population-based study to compare LBW (< 2500 g) rates across six groups of women with self-identified race (N = 7,865,264)-White and Black Latina, foreign-born and US-born; non-Latina Black; and non-Latina White-creating 4 models for analysis: unadjusted (Model 1) and adjusted for sociodemographic factors (Model 2), sociodemographic plus medical risk factors (Model 3), and Model 3 factors plus smoking (Model 4). Results Infant LBW rate for Black Latinas (7.9%) was higher than White Latinas (5.6%) and varied by nativity: US-born (8.9%) versus foreign-born (6.1%). Among all study groups, US-born Black Latinas' LBW rate (8.9%) was second only to non-Latina Blacks (11.0%). In unadjusted Model 1, US-born Black Latinas had 81% (odds ratio [OR]: 1.81; 95% confidence interval [CI]: 1.74-1.88) and foreign-born Black Latinas had 22% (OR: 1.22; 95% CI 1.15-1.29) higher odds of LBW than non-Latina White women (reference group). However, in Model 2, ORs for foreign-born Black Latinas were nearly identical to non-Latina Whites (OR: 1.03; 95% CI 0.97-1.1), while US-born Black Latinas' odds were still 47% higher (OR: 1.47; 95% CI 1.42-1.53). Model 3 ORs for each group were similar to Model 2. Conclusions for Practice A significant subgroup of Latina women self-identify as Black, and their LBW rates are higher than White Latinas. Black Latinas born in the United States fare worse than their foreign-born counterparts, implicating negative effects of Black race specific to the US context.
| S-EPMC6439288 | biostudies-other