Perspective: Moving Toward Desirable Linoleic Acid Content in Infant Formula.

Infant formula should provide the appropriate nutrients and adequate energy to facilitate healthy infant growth and development. If conclusive data on quantitative nutrient requirements are not available, the composition of human milk (HM) can provide some initial guidance on the infant formula composition. This paper provides a narrative review of the current knowledge, unresolved questions, and future research needs in the area of HM fatty acid (FA) composition, with a particular focus on exploring appropriate intake levels of the essential FA linoleic acid (LA) in infant formula. The paper highlights a clear gap in clinical evidence as to the impact of LA levels in HM or formula on infant outcomes, such as growth, development, and long-term health. The available preclinical information suggests potential disadvantages of high LA intake in the early postnatal period. We recommend performing well-designed clinical intervention trials to create clarity on optimal levels of LA to achieve positive impacts on both short-term growth and development and long-term functional health outcomes.

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.

Longitudinal human milk macronutrients, body composition and infant appetite during early life.

BACKGROUND & AIMS: Breastfeeding is the gold standard infant feeding. Data on macronutrients in relation to longitudinal body composition and appetite are very scarce. The aim of this study was to investigate longitudinal human milk macronutrients at 1 and 3 months in association with body composition and appetite during early life in healthy, term-born infants. We hypothesized that infants receiving higher caloric human milk would have more body fat mass and satiate earlier. METHODS: In 133 exclusively breastfed infants (Sophia Pluto Cohort), human milk samples at 1 and 3 months were analyzed for macronutrients (fat, protein, carbohydrate) by MIRIS Human Milk Analyzer, with appetite assessment by Baby Eating Behavior Questionnaires. Fat mass (FM) and fat-free mass (FFM) were measured by PEA POD and DXA, and abdominal FM by ultrasound. RESULTS: Milk samples showed large differences in macronutrients, particularly in fat content. Protein and energy content decreased significantly from 1 to 3 months. Fat and carbohydrate content tended to decrease (p = 0.066 and 0.081). Fat (g/100 ml) and energy (kcal/100 ml) content at 3 months were associated with FM% at 6 months (ß 0.387 and 0.040, resp.) and gain in FM% from 1 to 6 months (ß 0.088 and 0.009, resp.), but not with FM% at 2 years. Carbohydrate content at 3 months tended to associate with visceral FM at 2 years (ß 0.290, p = 0.06). Infants receiving higher caloric milk were earlier satiated and finished feeding faster. CONCLUSIONS: Our longitudinal data show decreasing milk protein and energy content from age 1 to 3 months, while fat and carbohydrate tended to decrease. Macronutrient composition, particularly fat content, differed considerably between mothers. Milk fat and energy content at 3 months associated with gain in FM% from age 1 to 6 months, indicating that higher fat and energy content associate with higher gain in FM% during the critical window for adiposity programming. As infants receiving higher caloric breastfeeding were earlier satiated, this self-regulatory mechanism might prevent intake of excessive macronutrients. ONLINE TRIAL REGISTRY: NTR, NL7833.

An early-life diet containing large phospholipid-coated lipid globules programmes later-life postabsorptive lipid trafficking in high-fat diet- but not in low-fat diet-fed mice.

Feeding mice in early life a diet containing an experimental infant milk formula (Nuturis®; eIMF), with a lipid structure similar to human milk, transiently lowered body weight (BW) and fat mass gain upon Western-style diet later in life, when compared with mice fed diets based on control IMF (cIMF). We tested the hypothesis that early-life eIMF feeding alters the absorption or the postabsorptive trafficking of dietary lipids in later life. Male C57BL/6JOlaHsd mice were fed eIMF/cIMF from postnatal day 16-42, followed by low- (LFD, American Institute of Nutrition (AIN)-93 G, 7 wt% fat) or high-fat diet (HFD, D12451, 24 wt% fat) until day 63-70. Lipid absorption rate and tissue concentrations were determined after intragastric administration of stable isotope (2H or 13C) labelled lipids in separate groups. Lipid enrichments in plasma and tissues were analysed using GC-MS. The rate of triolein absorption was similar between eIMF and cIMF fed LFD: 3·2 (sd 1·8) and 3·9 (sd 2·1) and HFD: 2·6 (sd 1·7) and 3·8 (sd 3·0) % dose/ml per h. Postabsorptive lipid trafficking, that is, concentrations of absorbed lipids in tissues, was similar in the eIMF and cIMF groups after LFD. Tissue levels of absorbed TAG after HFD feeding were lower in heart (-42 %) and liver (-46 %), and higher in muscle (+81 %, all P < 0·05) in eIMF-fed mice. In conclusion, early-life IMF diet affected postabsorptive trafficking of absorbed lipids after HFD, but not LFD. Changes in postabsorptive lipid trafficking could underlie the observed lower BW and body fat accumulation in later life upon a persistent long-term obesogenic challenge.

Effects of an early life diet containing large phospholipid-coated lipid globules on hepatic lipid metabolism in mice.

We recently reported that feeding mice in their early life a diet containing a lipid structure more similar to human milk (eIMF, Nuturis) results in lower body weights and fat mass gain upon high fat feeding in later life, compared to control (cIMF). To understand the underlying mechanisms, we now explored parameters possibly involved in this long-term effect. Male C57BL/6JOlaHsd mice, fed rodent diets containing eIMF or cIMF from postnatal (PN) day 16-42, were sacrificed at PN42. Hepatic proteins were measured using targeted proteomics. Lipids were assessed by LC-MS/MS (acylcarnitines) and GC-FID (fatty-acyl chain profiles). Early life growth and body composition, cytokines, and parameters of bile acid metabolism were similar between the groups. Hepatic concentrations of multiple proteins involved in ß-oxidation (+ 17%) the TCA cycle (+ 15%) and mitochondrial antioxidative proteins (+ 28%) were significantly higher in eIMF versus cIMF-fed mice (p < 0.05). Hepatic L-carnitine levels, required for fatty acid uptake into the mitochondria, were higher (+ 33%, p < 0.01) in eIMF-fed mice. The present study indicates that eIMF-fed mice have higher hepatic levels of proteins involved in fatty acid metabolism and oxidation. We speculate that eIMF feeding programs the metabolic handling of dietary lipids.

Spontaneous liver disease in wild-type C57BL/6JOlaHsd mice fed semisynthetic diet.

Mouse models are frequently used to study mechanisms of human diseases. Recently, we observed a spontaneous bimodal variation in liver weight in C57BL/6JOlaHsd mice fed a semisynthetic diet. We now characterized the spontaneous variation in liver weight and its relationship with parameters of hepatic lipid and bile acid (BA) metabolism. In male C57BL/6JOlaHsd mice fed AIN-93G from birth to postnatal day (PN)70, we measured plasma BA, lipids, Very low-density lipoprotein (VLDL)-triglyceride (TG) secretion, and hepatic mRNA expression patterns. Mice were sacrificed at PN21, PN42, PN63 and PN70. Liver weight distribution was bimodal at PN70. Mice could be subdivided into two nonoverlapping groups based on liver weight: 0.6 SD 0.1 g (approximately one-third of mice, small liver; SL), and 1.0 SD 0.1 g (normal liver; NL; p<0.05). Liver histology showed a higher steatosis grade, inflammation score, more mitotic figures and more fibrosis in the SL versus the NL group. Plasma BA concentration was 14-fold higher in SL (p<0.001). VLDL-TG secretion rate was lower in SL mice, both absolutely (-66%, p<0.001) and upon correction for liver weight (-44%, p<0.001). Mice that would later have the SL-phenotype showed lower food efficiency ratios during PN21-28, suggesting the cause of the SL phenotype is present at weaning (PN21). Our data show that approximately one-third of C57BL/6JOlaHsd mice fed semisynthetic diet develop spontaneous liver disease with aberrant histology and parameters of hepatic lipid, bile acid and lipoprotein metabolism. Study designs involving this mouse strain on semisynthetic diets need to take the SL phenotype into account. Plasma lipids may serve as markers for the identification of the SL phenotype.

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.

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.

Programming effects of an early life diet containing large phospholipid-coated lipid globules are transient under continuous exposure to a high-fat diet.

Breast-feeding is associated with a lower risk of developing obesity during childhood and adulthood compared with feeding infant milk formula (IMF). Previous studies have shown that an experimental IMF (eIMF; comprising Nuturis®) programmed mouse pups for a lower body weight and fat mass gain in adulthood when challenged with a high-fat diet (HFD) compared with a control IMF (cIMF). Nuturis has a lipid composition and structure more similar to breast milk. Here, the long-term effects were tested of a similar eIMF, but with an adapted lipid composition and a cIMF, on body weight, glucose homoeostasis, liver and adipose tissue. Nutrient composition was similar for the eIMF and cIMF; the lipid fractions comprised approximately 50 % milk fat. C57BL/6JOlaHsd mice were fed cIMF or eIMF from postnatal day (PN) 16-42 followed by an HFD until PN168. Feeding eIMF v. cIMF in early life resulted in a lower body weight (-9 %) and body fat deposition (-14 %) in adulthood (PN105). The effect appeared transient, as from PN126 onwards, after 12 weeks' HFD, eIMF-fed mice caught up on controls and body and fat weights became comparable between groups. Glucose and energy metabolism were similar between groups. At dissection (PN168), eIMF-fed mice showed larger (+27 %) epididymal fat depots and a lower (-26 %) liver weight without clear morphological aberrations. Our data suggest the size and coating but not the lipid composition of IMF fat globules underlie the programming effect observed. Prolonged exposure to an HFD challenge partly overrules the programming effect of early diet.

A systematic review of the effects of increasing arachidonic acid intake on PUFA status, metabolism and health-related outcomes in humans.

We conducted a systematic review of randomised controlled trials (RCT) of increased intake of arachidonic acid (ARA) on fatty acid status and health outcomes in humans. We identified twenty-two articles from fourteen RCT. Most studies were conducted in adults. These used between 80 and 2000 mg ARA per d and were of 1-12 weeks duration. Supplementation with ARA doses as low as 80 mg/d increased the content of ARA in different blood fractions. Overall there seem to be few marked benefits for adults of increasing ARA intake from the typical usual intake of 100-200 mg/d to as much as 1000 mg/d; the few studies using higher doses (1500 or 2000 mg/d) also report little benefit. However, there may be an impact of ARA on cognitive and muscle function which could be particularly relevant in the ageing population. The studies reviewed here suggest no adverse effects in adults of increased ARA intake up to at least 1000-1500 mg/d on blood lipids, platelet aggregation and blood clotting, immune function, inflammation or urinary excretion of ARA metabolites. However, in many areas there are insufficient studies to make firm conclusions, and higher intakes of ARA are deserving of further study. Based on the RCT reviewed, there are not enough data to make any recommendations for specific health effects of ARA intake.

Postprandial Amino Acid Kinetics of Milk Protein Mixtures are Affected by Composition, But Not Denaturation, in Neonatal Piglets.

BACKGROUND: Multiple studies have indicated that formula-fed infants show a different growth trajectory compared with breastfed infants. The observed growth rates are suggested to be linked to higher postprandial levels of branched chain amino acids (BCAAs) and insulin related to differences in protein quality. OBJECTIVE: We evaluated the effects of milk protein denaturation and milk protein composition on postprandial plasma and hormone concentrations. METHODS: Neonatal piglets were bolus-fed randomly, in an incomplete crossover design, 2 of 3 milk protein solutions: native whey protein isolate (NWPI), denatured whey protein isolate (DWPI), or protein base ingredient, comprising whey and casein (PBI). Postprandial plasma amino acids (AAs), insulin, glucagon-like peptide 1, glucose, and paracetamol concentrations were assayed. Plasma responses were fitted with a model of first-order absorption with linear elimination. RESULTS: DWPI (91% denatured protein) compared with NWPI (91% native protein) showed lower essential amino acids (EAAs) (∼10%) and BCAA (13-19%) concentrations in the first 30-60 min. However, total amino acid (TAA) concentration per time-point and area under the curve (AUC), as well as EAA and BCAA AUC were not different. PBI induced a ∼30% lower postprandial insulin spike than NWPI, yet plasma TAA concentration at several time-points and AUC was higher in PBI than in NWPI. The TAA rate constant for absorption (k a) was twofold higher in PBI than in NWPI. Plasma BCAA levels from 60 to 180 min and AUC were higher in PBI than in NWPI. Plasma EAA concentrations and AUCs in PBI and NWPI were not different. CONCLUSIONS: Denaturation of WPI had a minimal effect on postprandial plasma AA concentration. The differences between PBI and NWPI were partly explained by the difference in AA composition, but more likely differences in protein digestion and absorption kinetics. We conclude that modifying protein composition, but not denaturation, of milk protein solutions impacts the postprandial amino acid availability in neonatal piglets.

Longitudinal Variation of Amino Acid Levels in Human Milk and Their Associations with Infant Gender.

It is discussed that specific amino acids (AAs) have functional roles in early life. Understanding the AA composition in human milk (HM) during lactation assists in specifying these roles. To this end we assessed the levels of free AAs (FAAs), total AAs (free and bound, TAAs) and protein levels in HM in the first 6 months of lactation, and evaluated possible associations with infant gender. HM samples of 25 healthy Dutch mothers participating in the PreventCD study were collected monthly during the first 6 months of lactation. Of the participating mothers, 12 gave birth to a boy and 13 gave birth to a girl. Analyses of the HM samples revealed that levels of free glutamate, glutamine, aspartate, glycine, and serine significantly increased during months 1⁻3 of lactation, both in absolute sense and relative to TAA levels. Evaluation of gender differences by mixed model analyses revealed an association between female infant gender and higher protein content (p = 0.0465) and TAA content (p = 0.0362) in HM during the first 3 months of lactation. Furthermore, there was a tendency for an association of male infant gender with higher levels of free glutamine (p = 0.0948) in HM during the first 3 months of lactation. These results show that FAA, TAA and protein levels in HM display a time-specific occurrence during lactation. Moreover, although confirmation is necessary in view of the small sample size, this study indicates that the AA composition in HM shows differential effects of the infant's sex.

Growth and Clinical Variables in Nitrogen-Restricted Piglets Fed an Adjusted Essential Amino Acid Mix: Effects of Partially Intact Protein-Based Diets.

Background: Current recommendations for protein levels in infant formula are intended to ensure that growth matches or exceeds growth of breastfed infants, but may provide a surplus of amino acids (AAs). Recent infant studies with AA-based formulas support specific adjustment of the essential amino acid (EAA) composition allowing for potential lowering of total protein levels. With the use of a combination of intact protein and free EAAs, we designed a formula that meets these adjusted EAA requirements for infants. Objective: Our objective was to test whether this adjusted formula is safe and supports growth in a protein-restricted piglet model, and whether it shows better growth than an isonitrogenous formula based on free AAs. Methods: Term piglets (Landrace × Yorkshire × Duroc, n = 72) were fed 1 of 4 isoenergetic formulas containing 70% intact protein and 30% of an EAA mixture or a complete AA-based control for 20 d: standard formula (ST-100), ST-100 with 25% reduction in proteinaceous nitrogen (ST-75), ST-75 with an adjusted EAA composition (O-75), or a diet as O-75, given as a complete AA-based diet (O-75AA). Results: After an initial adaptation period, ST-75 and O-75 pigs showed similar growth rates, both lower than ST-100 pigs (∼25 compared with 31 g · kg-1 · d-1, respectively). The O-75AA pigs showed further reduced growth rate (15 g · kg-1 · d-1) and fat proportion (both P < 0.05, relative to O-75). Conclusions: Formula based partly on intact protein is superior to AA-based formula in this experimental setting. The 25% lower, but EAA-adjusted, partially intact protein-based formula resulted in similar weight gain with a concomitant increased AA catabolism, compared with the standard 25% lower standard formula in artificially reared, protein-restricted piglets. Further studies should investigate if and how the specific EAA adjustments that allow for lowering of total protein levels will affect growth and body composition development in formula-fed infants.

Growth and Clinical Variables in Nitrogen-Restricted Piglets Fed an Adjusted Essential Amino Acid Mix: Effects of Free Amino Acid-Based Diets.

Background: Excess protein intake in early life has been linked to obesity and metabolic syndrome in later life. Yet protein, and in particular the essential amino acids (EAAs), need to be present in adequate quantity to support growth. Objective: With the use of a piglet model restricted in dietary amino acids (AAs), we compared the efficacy and safety of a standard formula with a low-AA formula containing an adjusted AA composition. Methods: Female piglets (3-7 d old; Landrace × Yorkshire × Duroc) were fed 1 of 4 isoenergetic AA-based formulas for 14 d (700 kJ · kg body weight-1 · d-1). The formulas contained a set control amount (44 g/L) and AA compositions referred to as the experimental standard (ST-100, n = 22), or 20% or 50% lower total AAs (respectively, ST-80, n = 19 and ST-50, n = 13), or 20% lower total AAs with an optimally adjusted EAA composition (O-80, n = 17). A series of clinical and paraclinical endpoints were measured. Results: Growth rates were similar for ST-100, O-80 and ST-80 piglets (all ∼15 g · kg-1 · d-1), whereas ST-50 had a markedly lower weight gain relative to all groups (all P < 0.05). Relative to ST-100, all groups with reduced AA intake showed ∼16% reduction in plasma albumin and ∼30% reduction in plasma urea (both P < 0.05). The absolute leucine oxidation rate was ∼30% lower for O-80 than for ST-100 piglets (P < 0.05). Conclusions: These data show that a 20% reduction in total AA intake for both the control (ST-80) and the adjusted AA (O-80) formula did not have any short-term adverse effects on growth in artificially reared, AA-restricted piglets. The lower absolute leucine oxidation rate observed in O-80 supports the development of an infant formula with an improved AA composition and a moderate reduction in total protein to support adequate growth in healthy infants.

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 < 0.02). The median GR and IR for solid breakfast were respectively 44% and 45% higher compared to the liquid product (p < 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.

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.

Maternal exposure to a Western-style diet causes differences in intestinal microbiota composition and gene expression of suckling mouse pups.

SCOPE: The long-lasting consequences of nutritional programming during the early phase of life have become increasingly evident. The effects of maternal nutrition on the developing intestine are still underexplored. METHODS AND RESULTS: In this study, we observed (1) altered microbiota composition of the colonic luminal content, and (2) differential gene expression in the intestinal wall in 2-week-old mouse pups born from dams exposed to a Western-style (WS) diet during the perinatal period. A sexually dimorphic effect was found for the differentially expressed genes in the offspring of WS diet-exposed dams but no differences between male and female pups were found for the microbiota composition. Integrative analysis of the microbiota and gene expression data revealed that the maternal WS diet independently affected gene expression and microbiota composition. However, the abundance of bacterial families not affected by the WS diet (Bacteroidaceae, Porphyromonadaceae, and Lachnospiraceae) correlated with the expression of genes playing a key role in intestinal development and functioning (e.g. Pitx2 and Ace2). CONCLUSION: Our data reveal that maternal consumption of a WS diet during the perinatal period alters both gene expression and microbiota composition in the intestinal tract of 2-week-old offspring.

Reduced linoleic acid intake in early postnatal life improves metabolic outcomes in adult rodents following a Western-style diet challenge.

The global increase in dietary n-6 polyunsaturated fatty acid (PUFA) intake has been suggested to contribute to the rise in obesity incidence. We hypothesized that reduced n-6 PUFA intake during early postnatal life improves adult body composition and metabolic phenotype upon a Western diet challenge. Male offspring of C57Bl/6j mice and Wistar rats were subjected to a control diet (CTRL; 3.16 En% linoleic acid [LA]) or a low n-6 PUFA diet (low LA; 1.36 En% LA) from postnatal days (PNs) 2 to 42. Subsequently, all animals were switched to a Western-style diet (2.54 En% LA) until PN98. We monitored body composition by dual-energy x-ray absorptiometry and glucose homeostasis by an intravenous glucose and insulin tolerance test in rats and by the homeostasis model assessment of insulin resistance (HOMA-IR) in mice. At PN98, plasma lipids, glucose, insulin, and adipokines were measured and adipocyte number and size were analyzed. In mice, the postnatal low-LA diet decreased fat accumulation during the adult Western-style diet challenge (-27% compared with CTRL, P < .001). Simultaneously, it reduced fasting triglyceride levels and lowered fasting resistin and leptin levels. In rats, the low-LA diet did not affect adult body composition, but decreased the number of retroperitoneal adipocytes and increased the number of large adipocytes. In conclusion, lowering dietary n-6 PUFA intake in early life protected against detrimental effects of an obesogenic diet in adulthood on metabolic homeostasis and fat mass accumulation.

Acute and Chronic Effects of Dietary Lactose in Adult Rats Are not Explained by Residual Intestinal Lactase Activity.

Neonatal rats have a high intestinal lactase activity, which declines around weaning. Yet, the effects of lactose-containing products are often studied in adult animals. This report is on the residual, post-weaning lactase activity and on the short- and long-term effects of lactose exposure in adult rats. Acutely, the postprandial plasma response to increasing doses of lactose was studied, and chronically, the effects of a 30% lactose diet fed from postnatal (PN) Day 15 onwards were evaluated. Intestinal lactase activity, as assessed both in vivo and in vitro, was compared between both test methods and diet groups (lactose vs. control). A 50%-75% decreased digestive capability towards lactose was observed from weaning into adulthood. Instillation of lactose in adult rats showed disproportionally low increases in plasma glucose levels and did not elicit an insulin response. However, gavages comprising maltodextrin gave rise to significant plasma glucose and insulin responses, indicative of a bias of the adult GI tract to digest glucose polymers. Despite the residual intestinal lactase activity shown, a 30% lactose diet was poorly digested by adult rats: the lactose diet rendered the animals less heavy and virtually devoid of body fat, whereas their cecum tripled in size, suggesting an increased bacterial fermentation. The observed acute and chronic effects of lactose exposure in adult rats cannot be explained by the residual intestinal lactase activity assessed.