Somatostatin in the rat periventricular nucleus: sex differences and effect of gonadal steroids

In the rat, the sexual dimorphism in growth hormone release is driven by sex steroids, and is suggested to result mainly from differences in somatostatin (SOM) release patterns from the median eminence. We studied the effect of gonadal steroids on SOM peptide-containing cells in the periventricular nucleus (PeVN) of ovariectomized (OVX) female rats, and compared these data with data from intact male rats. Adult female rats were treated with estradiol (E2) and/or progesterone (P), 3 months (long-term) or 2 weeks (short-term) after ovariectomy (OVX). Perfusion-fixed brains were sliced and stained, and the number of SOM-immunoreactive (-ir) cells and total SOM-ir area (in μm2) were determined using computer assisted analysis. SOM-ir cells in the PeVN showed a very characteristic rostro-caudal distribution and localization in relation to the third ventricle. Both the number of SOM-ir cells and total SOM-ir area in the PeVN were higher in male compared to OVX female rats. Neither the number of SOM-ir cells, nor the total SOM-ir area in the PeVN was affected by E2 or P treatment alone. Treatment with both gonadal steroids, however, did increase total SOM-immunoreactivity. This study is the first to describe SOM cell distribution within the rat PeVN in great detail. A clear sex difference exists in SOM peptide content in the rat PeVN. In addition, E2 and P may act synergistically to affect SOM cells in the female PeVN, suggesting that both gonadal steroids may be involved in the generation of the typical feminine SOM release pattern

Rapid and selective manipulation of milk fatty acid composition in mice through the maternal diet during lactation

Dietary fatty acid (FA) composition in early postnatal life can modulate growth and development and later metabolic health. Investigating programming effects of early dietary FA manipulations in rodents may be stressful and complicated due to the need of artificial feeding techniques. It is largely unknown to what extent breast milk (BM) FA composition can be directly manipulated by the diet. We exposed dams to different dietary FA compositions from postnatal day (PN) 2 until PN28. Dams with litters were randomly assigned to control (CTRL), high-medium-chain FA (MCFA), low-linoleic acid (LowLA), high-n-3 long-chain PUFA (n-3LCP) or high-n-3LCP and MCFA (n-3LCP/MCFA) diets, and diets were continued after weaning until PN28. FA compositions were determined in feeds, milk and in erythrocytes. BM MCFA content was independent from dietary MCFA intake. In contrast, the LowLA diet reduced BM LA content by about 50 % compared with the CTRL diet at PN7. BM of dams fed the n-3LCP or n-3LCP/MCFA diet contained about 6-fold more n-3 LCP than BM of the dams fed the CTRL diet at PN7. These changes in milk FA composition established after 5 d of dietary exposure did not further change over the lactation period. At PN28, the erythrocyte FA composition of the male pups correlated with analysed milk FA profiles. In conclusion, manipulation of the diet of lactating mice can strongly and rapidly affect BM FA composition, in particular of n-6 LA and n-3 LCP. Our present findings will facilitate mechanistic studies on the programming of adult metabolic health by dietary FA in the early postnatal period via direct and selective manipulation of the maternal diet

М.К. Янгель біля витоків вітчизняного ракетобудування

Висвітлено життєвий шлях академіка М.К.Янгеля, його внесок у розвиток вітчизняного ракетобудування, забезпечення обороноздатності СРСР.Освещены жизненный путь академика М.К.Янгеля и его вклад в развитие отечественного ракетостроения, обеспечение обороноспособности СССР.An account of the life path of the academician М. К. Yangel, his contribution in the national spacecraft and of defense capacity building of the USSR is contained

A modified low-protein infant formula supports adequate growth in healthy, term infants:a randomized, double-blind, equivalence trial

Background: A high protein intake in early life is associated with a risk of obesity later in life. The essential amino acid requirements of formula-fed infants have been reassessed recently, enabling a reduction in total protein content and thus in protein intake. Objectives: We aimed to assess the safety of an infant formula with a modified amino acid profile and a modified low-protein (mLP) content in healthy term-born infants. Outcomes were compared with a specifically designed control (CTRL) infant formula. Methods: In this double-blind, randomized controlled equivalence trial, infants received either mLP (1.7 g protein/100 kcal; n = 90) or CTRL formula (2.1 g protein/100 kcal; n = 88) from enrollment (age ≤ 45 d) to 6 mo of age. A breastfed group served as a reference (n = 67). Anthropometry and body composition were determined at baseline, 17 wk (including safety blood parameters), and 6 mo of age. The primary outcome was daily weight gain from enrollment up until the age of 17 wk (at an equivalence margin of ±3.0 g/d). Results: Weight gain from baseline (mean ± SD age: 31 ± 9 d) up to the age of 17 wk was equivalent between the mLP and CTRL formula groups (27.9 and 28.8 g/d, respectively; difference:-0.86 g/d; 90% CI:-2.36, 0.63 g/d). No differences in other growth parameters, body composition, or in adverse events were observed. Urea was significantly lower in the mLP formula group than in the CTRL formula group (-0.74 mmol/L; 95% CI:-0.97,-0.51 mmol/L; P < 0.001). Growth rates, fat mass, fat-free mass, and several essential amino acids were significantly higher in both formula groups than in the breastfed reference group. Conclusions: Feeding an infant formula with a modified amino acid profile and a lower protein content from an average age of 1 mo until the age of 6 mo is safe and supports an adequate growth, similar to that of infants consuming CTRL formula. This trial was registered at www.trialregister.nl as Trial NL4677

An Increased Dietary Supply of Medium-Chain Fatty Acids during Early Weaning in Rodents Prevents Excessive Fat Accumulation in Adulthood

Medium-chain fatty acids (MCFA) are a directly and readily absorbed source of energy. Exposure early-in-life to increased MCFA levels might affect development and impact (lipid) metabolism later in life. We tested whether an increased MCFA intake early-in-life positively affects adult body composition and metabolic status when challenged by a western-style diet (WSD). Male offspring of C57Bl/6j mice and Wistar rats were fed a control diet (CTRL; 10 w% fat, 14% MCFA) or a medium-chain triglycerides (MCT) diet with 20% MCFA until postnatal (PN) day 42, whereupon animals were fed a WSD (10 w% fat) until PN day 98. Body composition was monitored by Dual Energy X-ray Absorptiometry (DEXA). In rats, glucose homeostasis was assessed by glucose tolerance test (GTT) and insulin tolerance test (ITT); in mice, the HOmeostasis Model Assessment of Insulin Resistance (HOMA-IR) was calculated. At autopsy on PN day 98, plasma lipid profiles, glucose, insulin, and adipokines were measured; organs and fat pads were collected and the adipocyte size distribution was analysed. Milk analysis in mice showed that the maternal MCT diet was not translated into milk, and pups were thus only exposed to high MCT levels from early weaning onward: PN day 16 until 42. Mice exposed to MCT showed 28% less fat accumulation vs. CTRL during WSD. The average adipocyte cell size, fasting plasma triglycerides (TG), and leptin levels were reduced in MCT mice. In rats, no effects were found on the adult body composition, but the adipocyte cell size distribution shifted towards smaller adipocytes. Particularly mice showed positive effects on glucose homeostasis and insulin sensitivity. Increased MCFA intake early-in-life protected against the detrimental effects of an obesogenic diet in adulthood

Macronutrient Composition and Food Form Affect Glucose and Insulin Responses in Humans

Glycaemic index (GI) is used as an indicator to guide consumers in making healthier food choices. We compared the GI, insulin index (II), and the area under the curve for blood glucose and insulin as glucose (GR) and insulin responses (IR) of a newly developed liquid nutritional formula with one commercially available liquid product with different types of carbohydrates. We then evaluated the glucose and insulin responses of two test foods with comparable energy density and protein percentage but presented in different food forms (liquid vs. solid). Fourteen healthy women participated in the study. GI, II, GR, and IR were assessed after (independent) consumption of two liquid products and a solid breakfast meal. The two liquid foods showed comparable GI, whilst the liquid form appeared to produce lower median GI (25 vs. 54), and II (52 vs. 98) values compared to the solid breakfast (p &lt; 0.02). The median GR and IR for solid breakfast were respectively 44% and 45% higher compared to the liquid product (p &lt; 0.02). Liquid formulas with different carbohydrate qualities produced comparable glucose responses, while foods with comparable energy density and protein percentage but different food form elicited differential effects on GI, II, GR, and IR. Nutrient quality and food form need to be taken into consideration when developing low GI products to manage glycaemic responses

Perinatal exposure of rats to a maternal diet with varying protein quantity and quality affects the risk of overweight in female adult offspring

The maternal protein diet during the perinatal period can program the health of adult offspring. This study in rats evaluated the effects of protein quantity and quality in the maternal diet during gestation and lactation on weight and adiposity in female offspring. Six groups of dams were fed a high-protein (HP; 47% protein) or normal-protein (NP; 19% protein) isocaloric diet during gestation (G) using either cow's milk (M), pea (P) or turkey (T) proteins. During lactation, all dams received the NP diet (protein source unchanged). From postnatal day (PND) 28 until PND70, female pups (n=8) from the dam milk groups were exposed to either an NP milk diet (NPMW) or to dietary self-selection (DSS). All other pups were only exposed to DSS. The DSS design was a choice between five food cups containing HPM, HPP, HPT, carbohydrates or lipids. The weights and food intakes of the animals were recorded throughout the study, and samples from offspring were collected on PND70. During the lactation and postweaning periods, body weight was lower in the pea and turkey groups (NPG and HPG) versus the milk group (P<.0001). DSS groups increased their total energy and fat intakes compared to the NPMW group (P<.0001). In all HPG groups, total adipose tissue was increased (P=.03) associated with higher fasting plasma leptin (P<.05). These results suggest that the maternal protein source impacted offspring body weight and that protein excess during gestation, irrespective of its source, increased the risk of adiposity development in female adult offspring

Long-term effects of a modified, low-protein infant formula on growth and body composition:Follow-up of a randomized, double-blind, equivalence trial

Background & aim: High protein intake in early life is associated with an increased risk of childhood obesity. Feeding a modified lower-protein (mLP) infant formula (1.7 g protein/100 kcal) until the age of 6 months is safe and supports adequate growth. The aim of the present study is to assess longer-term anthropometry with BMI at 1 and 2 years as primary outcome parameter and body composition in children fed mLP formula. Methods: Healthy term-born infants received mLP or control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double-blinded RCT. A breast-fed (BF) group served as a reference. Anthropometry data were obtained at 1 and 2 years of age. At the age of 2 years, body composition was measured with air-displacement plethysmography. Groups were compared using linear mixed model analysis. Results: At 1 and 2 years of age, anthropometry, including BMI, and body composition did not differ between the formula groups (n = 74 mLP; n = 69 CTRL). Compared to the BF group (n = 51), both formula-fed groups had higher z scores for weight for age, length for age, waist circumference for age, and mid-upper arm circumference for age at 1 year of age, but not at 2 years of age (except for z score of weight for age in the mLP group). In comparison to the BF group, only the mLP group had higher fat mass, fat-free mass, and fat mass index. However, % body fat did not differ between feeding groups. Conclusions: In this follow-up study, no significant differences in anthropometry or body composition were observed until 2 years of age between infants fed mLP and CTRL formula, despite the significantly lower protein intake in the mLP group during the intervention period. The observed differences in growth and body composition between the mLP group and the BF reference group makes it necessary to execute new trials evaluating infant formulas with improved protein quality together with further reductions in protein content. Clinical Trial Registry: This trial was registered in the Dutch Trial Register (Study ID number NTR4829, trial number NL4677). https://www.trialregister.nl/trial/4677

Early-Life Metabolic and Hormonal Markers in Blood and Growth until Age 2 Years:Results from a Randomized Controlled Trial in Healthy Infants Fed a Modified Low-Protein Infant Formula

Background: High protein intake in early life is associated with an increased risk of childhood obesity. Dietary protein intake may be a key mechanistic modulator through alterations in endocrine and metabolic responses. Objective: We aimed to determine the impact of different protein intake of infants on blood metabolic and hormonal markers at the age of four months. We further aimed to investigate the association between these markers and anthropometric parameters and body composition until the age of two years. Design: Term infants received a modified low-protein formula (mLP) (1.7 g protein/100 kcal) or a specifically designed control formula (CTRL) (2.1 g protein/100 kcal) until 6 months of age in a double blinded RCT. The outcomes were compared with a breast-fed (BF) group. Glucose, insulin, leptin, IGF-1, IGF-BP1, -BP2, and -BP3 levels were measured at the age of 4 months. Anthropometric parameters and body composition were assessed until the age of 2 years. Groups were compared using linear regression analysis. Results: No significant differences were observed in any of the blood parameters between the formula groups (n = 53 mLP; n = 44 CTRL) despite a significant difference in protein intake. Insulin and HOMA-IR were higher in both formula groups compared to the BF group (n = 36) (p < 0.001). IGF-BP1 was lower in both formula groups compared to the BF group (p < 0.01). We found a lower IGF-BP2 level in the CTRL group compared to the BF group (p < 0.01) and a higher IGF-BP3 level in the mLP group compared to the BF group (p = 0.03). There were no significant differences in glucose, leptin, and IGF-1 between the three feeding groups. We found specific associations of all early-life metabolic and hormonal blood parameters with long-term growth and body composition except for IGF-1. Conclusions: Reducing protein intake by 20% did not result in a different metabolic profile in formula-fed infants at 4 months of age. Formula-fed infants had a lower insulin sensitivity compared to breast-fed infants. We found associations between all metabolic and hormonal markers (except for IGF-1) determined at age 4 months and growth and body composition up to two years of age