The Influence of Maternal Obesity and Breastfeeding on Infant Appetite- and Growth-Related Hormone Concentrations: The SKOT Cohort Studies.

BACKGROUND/AIMS: Exposure to obesity during pregnancy may lead to adverse changes in the offspring's metabolic profile. We compared appetite- and growth-related hormones in a cohort of infants born to obese mothers (SKOT-II) with infants born mainly to nonobese mothers (SKOT-I). METHODS: Infants from SKOT-I (n = 273) and SKOT-II (n = 132) were examined including anthropometric measurements and blood samples analyzed for glucose, insulin, insulin-like growth factor-I (IGF-I), adiponectin, and leptin. Information on breastfeeding and parental characteristics were also collected. RESULTS: At 9 months of age, SKOT-II infants were 3.6% heavier and 1.2% longer than SKOT-I infants even though their mothers were shorter. There was no difference in body mass index (BMI). SKOT-II infants had higher levels of insulin, adiponectin, and leptin but lower levels of IGF-I compared to SKOT-I infants (all p ≤ 0.015). These differences remained, except for leptin, when adjusted for current weight. Breastfeeding versus nonbreastfeeding at 9 months was associated with lower concentrations of all hormones (all p ≤ 0.003). In adjusted models, maternal BMI at 9 months was positively associated with insulin and adiponectin and negatively with IGF-I. CONCLUSIONS: Pre-pregnancy obesity confers symmetrically larger infant body size and higher levels of most growth- and appetite-related hormones but surprisingly lower levels of IGF-I, suggesting other possible infant growth-promoting effects through insulin

The role of leptin and other hormones related to bone metabolism and appetite regulation as determinants of gain in body fat and fat-free mass in 8-11-year-old children.

BACKGROUND: Regulation of body composition during childhood is complex. Numerous hormones are potentially involved. Leptin has been proposed to restrain weight gain, but results are inconsistent. OBJECTIVE: We examined whether baseline fasting levels of ghrelin, adiponectin, leptin, insulin, IGF-I, osteocalcin, and intact parathyroid hormone (iPTH) were associated with body composition cross sectionally and longitudinally in 633 8-11-year-olds. DESIGN: Data on hormones and body composition by dual-energy x-ray absorptiometry from the OPUS School Meal Study were used. We looked at baseline hormones as predictors of baseline fat mass index (FMI) or fat-free mass index (FFMI), and also subsequent changes (3 and 6 months) in FMI or FFMI using models with hormones individually or combined. RESULTS: Cross-sectionally, baseline leptin was positively associated with FMI in girls (0.211 kg/m(2) pr. μg/mL; 97.5% confidence interval [CI],0.186-0.236; P < .001) and boys (0.231 kg/m(2) pr. μg/mL; 97.5% CI, 0.200-0.261; P < .001). IGF-I in both sexes and iPTH in boys were positively associated with FMI. An inverse association between adiponectin and FFMI in boys and a positive association between IGF-I and FFMI were found in girls. In longitudinal models, baseline leptin was inversely associated with subsequent changes in FMI (-0.018 kg/m(2) pr. μg/mL; 97.5% CI, -0.034 - -0.002; P = .028) and FFMI (-0.014 kg/m(2) pr. μg/mL; 97.5% CI, -0.024 - -0.003; P = .006) in girls. CONCLUSIONS: Cross-sectional findings support that leptin is produced in proportion to body fat mass, but the longitudinal observations support that leptin inhibits gains in FMI and FFMI in girls, a finding that may reflect preserved leptin sensitivity in this predominantly normal weight population.Address all correspondence and requests for reprints to: Stine-Mathilde Dalskov, Department of Nutrition, Exercise and Sports, University of Copenhagen, Rolighedsvej 26, 1958 Frederiksberg C, Denmark. E-mail: [email protected]. This study was registered inClinicalTrials.gov as trial number NCT01457794. The OPUS study was financed by a Grant from the Nordea Foundation (grant number 02-2010-478 0389). A complete list of food suppliers providing full or partial food sponsorships to the study can be found at the website: http://foodoflife.ku.dk/ opus/wp/skolemadsprojektet/leverandorer. Sources of funding and donation had no role in the trial design; collection, analysis, interpretation of data or decision to publish.This is the accepted manuscript for a paper published in Journal of Clinical Endocrinology and Metabolism, March 2015, 100(3):1196 –1205, DOI: 10.1210/jc.2014-370

Associations of fat mass and fat-free mass accretion in infancy with body composition and cardiometabolic risk markers at 5 years:The Ethiopian iABC birth cohort study

BackgroundAccelerated growth in early childhood is an established risk factor for later obesity and cardiometabolic disease, but the relative importance of fat mass (FM) and fat-free mass (FFM) accretion is not well understood. We aimed to study how FM and FFM at birth and their accretion during infancy were associated with body composition and cardiometabolic risk markers at 5 years.Methods and findingsHealthy children born at term were enrolled in the Infant Anthropometry and Body Composition (iABC) birth cohort between December 2008 and October 2012 at Jimma University Specialized Hospital in the city of Jimma, Ethiopia. FM and FFM were assessed using air displacement plethysmography a median of 6 times between birth and 6 months of age. In 507 children, we estimated individual FM and FFM at birth and their accretion over 0-3 and 3-6 months of age using linear-spline mixed-effects modelling. We analysed associations of FM and FFM at birth and their accretion in infancy with height, waist circumference, FM, FFM, and cardiometabolic risk markers at 5 years using multiple linear regression analysis. A total of 340 children were studied at the 5-year follow-up (mean age: 60.0 months; girls: 50.3%; mean wealth index: 45.5 out of 100; breastfeeding status at 4.5 to 6 months post-partum: 12.5% exclusive, 21.4% almost exclusive, 60.6% predominant, 5.5% partial/none). Higher FM accretion in infancy was associated with higher FM and waist circumference at 5 years. For instance, 100-g/month higher FM accretion in the periods 0-3 and 3-6 months was associated with 339 g (95% CI: 243-435 g, p ConclusionsFM accretion in early life was positively associated with markers of adiposity and lipid metabolism, but not with blood pressure and cardiometabolic markers related to glucose homeostasis. FFM accretion was primarily related to linear growth and FFM at 5 years

Higher weight and weight gain after 4 years of age rather than weight at birth are associated with adiposity, markers of glucose metabolism, and blood pressure in 5-year-old Ethiopian children

BACKGROUND: Fetal and early life growth is associated with adult risk of obesity and cardiometabolic disease. However, little is known about the relative importance of birth weight and successive periods of weight gain on markers of cardiometabolic risk in childhood in low-income populations. // OBJECTIVES: The objective was to study associations of birth weight and weight gain velocities in selected age intervals from birth to 60 mo with height, fat-free mass (FFM), and markers of adiposity and cardiometabolic risk at 60 mo. // METHODS: In a prospective cohort study of 375 Ethiopian children aged 60 mo, we estimated individual weight gain velocities in the periods between birth and 3, 6, 24, 48, and 60 mo using linear-spline mixed-effects modeling. Subsequently, we analyzed associations of birth weight, weight gain velocities, and current weight with height, FFM, and markers of adiposity and cardiometabolic risk. // RESULTS: Weight gain from 48 to 60 mo and weight at 60 mo rather than birth weight were the strongest correlates of insulin, C-peptide, HOMA-IR, blood pressure, height, FFM, waist circumference, and fat mass at 60 mo. For instance, 1 SD higher (1 SD = 50 g/mo) weight accretion from 48 to 60 mo was associated with a higher insulin of 23.3% (95% CI: 9.6%, 38.8%), C-peptide of 11.4% (2.7%, 20.8%), systolic blood pressure of 1.4 mm Hg (0.6, 2.3 mm Hg), fat mass of 0.72 kg (0.59, 0.85 kg), and FFM of 0.70 kg (0.56, 0.85 kg). Weight gain from 0 to 3 mo was positively associated with LDL cholesterol, systolic blood pressure, height, and the body composition indices, and weight gain from 24 to 48 mo was inversely associated with blood glucose. // CONCLUSIONS: In 60-mo-old Ethiopian urban children, weight gain and weight after 48 mo rather than weight at birth may represent a sensitive period for variations in markers of adiposity and glucose metabolism. The birth cohort is registered at https://www.isrctn.com/ as ISRCTN46718296

Targeting the glycine-rich domain of TDP-43 with antibodies prevents its aggregation in vitro and reduces neurofilament levels in vivo

Cytoplasmic aggregation and concomitant nuclear clearance of the RNA-binding protein TDP-43 are found in similar to 90% of cases of amyotrophic lateral sclerosis and similar to 45% of patients living with frontotemporal lobar degeneration, but no disease-modifying therapy is available. Antibody therapy targeting other aggregating proteins associated with neurodegenerative disorders has shown beneficial effects in animal models and clinical trials. The most effective epitopes for safe antibody therapy targeting TDP-43 are unknown. Here, we identified safe and effective epitopes in TDP-43 for active and potential future passive immunotherapy. We prescreened 15 peptide antigens covering all regions of TDP-43 to identify the most immunogenic epitopes and to raise novel monoclonal antibodies in wild-type mice. Most peptides induced a considerable antibody response and no antigen triggered obvious side effects. Thus, we immunized mice with rapidly progressing TDP-43 proteinopathy (rNLS8 model) with the nine most immunogenic peptides in five pools prior to TDP-43 Delta NLS transgene induction. Strikingly, combined administration of two N-terminal peptides induced genetic background-specific sudden lethality in several mice and was therefore discontinued. Despite a strong antibody response, no TDP-43 peptide prevented the rapid body weight loss or reduced phospho-TDP-43 levels as well as the profound astrogliosis and microgliosis in rNLS8 mice. However, immunization with a C-terminal peptide containing the disease-associated phosphoserines 409/410 significantly lowered serum neurofilament light chain levels, indicative of reduced neuroaxonal damage. Transcriptomic profiling showed a pronounced neuroinflammatory signature (IL-1 beta, TNF-alpha, Nf-kappa B) in rNLS8 mice and suggested modest benefits of immunization targeting the glycine-rich region. Several novel monoclonal antibodies targeting the glycine-rich domain potently reduced phase separation and aggregation of TDP-43 in vitro and prevented cellular uptake of preformed aggregates. Our unbiased screen suggests that targeting the RRM2 domain and the C-terminal region of TDP-43 by active or passive immunization may be beneficial in TDP-43 proteinopathies by inhibiting cardinal processes of disease progression

Effect of complementary food with small amounts of freshwater fish on whole blood n-3 fatty acids in Cambodian infants age 6-15 months

The final publication is available at Elsevier via https://dx.doi.org/10.1016/j.plefa.2018.07.002”. © 2018. This manuscript version is made available under the CC-BY-NC-ND 4.0 license http://creativecommons.org/licenses/by-nc-nd/4.0/The impact of freshwater fish consumption on the status of long-chain n-3 fatty acids (n-3 LCPUFA) in infants in landlocked, low-income populations is unknown. We used secondary data from a randomized, single-blinded, controlled trial to evaluate the impact of daily consumption of complementary food products with small amounts of freshwater fish on whole blood n-3 LCPUFA in Cambodian infants. Infants (n=419), received daily, one of four food products for 9 months. Two products contained freshwater fish: WinFood (10% fish by dry weight) and WinFood-L (12% fish by dry weight), while two products were non-fish-based: corn-soy blends (CSB+ and CSB++). Whole blood fatty acids and breastfeeding status were assessed at baseline and endline of the intervention. The WinFood products contributed to an estimated maximum intake of 86.5 mg/day n-3 LCPUFA. There was no difference in whole blood n-3 LCPUFA among the four intervention groups or between the fish-based and the non-fish-based groups (p≥0.142). At endline, 71% of the children were still breastfed. Interaction analyses indicated a lower ratio of n-6/n-3 PUFA in non-breastfed infants in the WinFood groups compared to the CSB groups (pinteraction=0.026). Thus, a high intake of n-3 LCPUFA from breastmilk may have blurred a potential impact of small amounts of freshwater fish effect on n-3 LCPUFA status in Cambodian infants.Danida || 57-08-LIFEEuropean Commission || SMILING Project 289616Institut de Recherche pour le DéveloppementUniversity of CopenhagenCanada Research Chair in Nutritional LipidomicsWorld Food Programm

Children with moderate acute malnutrition have inflammation not explained by maternal reports of illness and clinical symptoms: a cross-sectional study in Burkina Faso

Background Morbidity plays an important role in the development of and recovery from malnutrition. Morbidity in children with moderate acute malnutrition (MAM) has not been described in detail and it is unclear how morbidity compares to serum levels of acute phase proteins (APPs) which indicate systemic inflammation and which can impede response to therapeutic nutritional interventions. The objective of this study was to describe morbidity in children with MAM and to assess to what extent maternally reported and clinically diagnosed morbidity explain the variation in APPs. Methods A cross-sectional sub study was conducted as part of a nutrition intervention trial among 6–23 months old children with MAM residing in Burkina Faso. Morbidity data collection at baseline included 2 week maternal recalls and physical examinations. Multivariate ANCOVA models were used to explore the associations between morbidity and C-reactive protein (CRP) as well as α1-acid glycoprotein (AGP). These models were also used to determine to what extent morbidity explains variation in APPs. Results In the 2 weeks prior to the study inclusion visit, 38 % of children were ill according to mothers. Furthermore, 71.8 % of children had a symptom or infection identified during the physical examination and 24.2 and 66.4 % of children had elevated CRP and AGP, respectively. Among children without any identified symptom or illness at the inclusion visit, 10.7 and 46.5 % had elevated CRP and AGP, respectively. History of fever as well as nurse-documented fever, malaria, respiratory tract infections and skin infections were associated with higher levels of both APPs. History of cough and diarrhoea at the inclusion visit was associated with higher α1-acid glycoprotein only. Overall, morbidity data only explained a small amount of the variation in APP levels (adjusted R2 below 0.2 in all tested models). Conclusion Morbidity among children with MAM in this setting is common, but maternal reports and clinical examination explained only a small proportion of the variation in APPs, indicating a presence of subclinical inflammation. We recommend further research into the causes of this subclinical inflammation as it could affect nutritional status and success of MAM treatment.BioMed Central open acces