Metabolic Regulation of Pre- and Postnatal Growth.

Growth characteristics during periods of early developmental plasticity are linked with later health outcomes and with disease risks. Infant growth is modulated by genetic and exogenous factors including nutrition. We try to explore their underlying mechanisms using targeted metabolomic profiling of small molecules in biological samples using high-performance liquid chromatography (LC) coupled to tandem mass spectrometry (MS/MS) to quantify hundreds of molecules in small biosamples, e.g., 50 µL plasma. In the large German LISA birth cohort study, cord blood lysophosphatidylcholines and fatty acids were closely associated with infant birth weight, with a nonsignificant trend towards an association with infant weight gain and later BMI. Studies in infants randomized to different protein intakes in the European CHOP Study show conventional high protein intakes to markedly increase plasma-indispensable amino acids (AA), particularly branched-chain AA (BCAA), while exceeding the infant's capacity of BCAA breakdown, and an increase in the dispensable AA tyrosine previously associated with insulin resistance. In a path model analysis of the relationship of infant plasma AA, growth factors, and infant growth, AA were generally found to induce a stronger response of insulin than IGF-I although effects of individual AA were very different. We conclude that targeted improvement in nutrient supply in pregnancy and infancy may offer large opportunities for promoting desirable child growth patterns and long-term health.

Associations of IGF-1 gene variants and milk protein intake with IGF-I concentrations in infants at age 6 months - results from a randomized clinical trial.

OBJECTIVE: The interplay of genetic and nutritional regulation of the insulin-like growth factor-I axis in children is unclear. Therefore, potential gene-nutrient effects on serum levels of the IGF-I axis in a formula feeding trial were studied. DESIGN: European multicenter randomized clinical trial of 1090 term, formula-fed infants assigned to receive cow's milk-based infant and follow-on formulae with lower (LP: 1.25 and 1.6 g/100 mL) or higher (HP: 2.05 and 3.2 g/100 mL) protein contents for the first 12 months of life; a comparison group of 588 breastfed infants (BF) was included. Eight single nucleotide polymorphisms (SNPs) of the IGF-1-(rs6214, rs1520220, rs978458, rs7136446, rs10735380, rs2195239, rs35767, and rs35766) and two of the IGFBP-3-(rs1496495, rs6670) gene were analyzed. Serum levels of total and free IGF-I, IGFBP-3 and the molar ratio IGF-1/IGFBP-3 at age 6 months were regressed on determined SNPs and feeding groups in 501 infants. RESULTS: IGF-1-SNPs rs1520220, rs978458, and rs2195239 significantly increased total-IGF-I and molar-ratio IGF-I/IGFBP-3 by ~1.3 ng/mL and ~1.3 per allele, respectively; compared to LP infants concentration and molar-ratio were increased in HP by ~1.3 ng/mL and ~1.3 and decreased in BF infants by ~0.6 ng/mL and ~0.6, respectively. IGFBP-3 was only affected by the BF group with ~450 ng/mL lower levels than the LP group. No gene-feeding-group interaction was detected for any SNP, even without correction for multiple testing. CONCLUSIONS: Variants of the IGF-1-gene play an important role in regulating serum levels of the IGF-I axis but there is no gene-protein-interaction. The predominant nutritional regulation of IGF-I and IGFBP-3 gives further evidence that higher protein intake contributes to metabolic programming of growth.

Early influences of nutrition on postnatal growth.

Health and nutrition modulate postnatal growth. The availability of amino acids and energy, and insulin and insulin-like growth factor-I (IGF-I) regulates early growth through the mTOR pathway. Amino acids and glucose also stimulate the secretion of IGF-I and insulin. Postnatal growth induces lasting, programming effects on later body size and adiposity in animals and in human observational studies. Rapid weight gain in infancy and the first 2 years was shown to predict increased obesity risk in childhood and adulthood. Breastfeeding leads to lesser high weight gain in infancy and reduces obesity risk in later life by about 20%, presumably partly due to the lower protein supply with human milk than conventional infant formula. In a large randomized clinical trial, we tested the hypothesis that reduced infant formula protein contents lower insulin-releasing amino acid concentrations and thereby decrease circulating insulin and IGF-I levels, resulting in lesser early weight gain and reduced later obesity risk (the 'Early Protein Hypothesis'). The results demonstrate that lowered protein in infant formula induces similar - but not equal - metabolic and endocrine responses and normalizes weight and BMI relative to breastfed controls at the age of 2 years. The results available should lead to enhanced efforts to actively promote, protect and support breastfeeding. For infants that are not breastfed or not fully breastfed, the use of infant formulas with lower protein contents but high protein quality appears preferable. Cows' milk as a drink provides high protein intake and should be avoided in infancy.

Pollen-wall formation in Arum alpinum.

BACKGROUND AND AIMS: Arum alpinum has a quite uncommon pollen wall. A sporopolleninous ektexine is missing. The outermost pollen wall layer is formed by the endexine which is covered by polysaccharidic ornamentation elements. An ontogenetical investigation was accomplished to clarify pollen-wall development, with special reference to callose and pollen-wall development. METHODS: Plants of Arum alpinum grown in their natural habitat were collected once a week within the vegetative period and processed for semi- and ultra-thin sectioning. KEY RESULTS: At any stage of pollen-wall formation callose is missing. Microspores are released from the tetrad by invagination of the amoeboid tapetum. The polysaccharidic wall ornamentations are formed by the tapetum. CONCLUSIONS: There appears to be no truth in the dogma that callose is essential for microspore separation and release from the tetrad. The lack of callose does not influence fertility but could be the reason for the uncommon pollen wall, where a sporopolleninous ektexine is missing.