Early-life programming is becoming an established concept that states that the environment during early development affects health and disease in adulthood, probably via epigenetic mechanisms such as DNA methylation, histone modifications, RNA silencing, or a combination. Accumulating evidence suggests that nutrition during pregnancy and early postnatal life is one of the most important environmental cues that programs microbiological, metabolic, and immunologic development. The neonatal period is crucial for the early microbial colonization of the almost sterile gastrointestinal tract of the newborn infant. These first colonizers play an important role in host health because they are involved in nutritional, immunologic, and physiologic functions. Evidence from animal and human studies indicates that the composition of the gut microbiota has an effect on body composition, digestion, and metabolic homeostasis. Furthermore, the functionality of the metabolism develops after birth when the newborn is first exposed to nutrition via the gastrointestinal tract. Exposure to environmental microbial components is also suggested to have a key role in the maturation process of the immune system, and in turn the immune system shapes the composition of the microbiota. Therefore, the use of nutritional strategies to program the microbiota composition to favor a more beneficial bacterial population and to support the development of the metabolic and immune systems may provide a good opportunity to prevent later health problems such as obesity, diabetes, and allergy.

CD2F1 mice were inoculated with C26 adenocarcinoma cells, followed by assessment of ex vivo muscular function. Muscles from tumor-bearing mice had a significantly lower force output during a single maximal contraction and during repeated contractions than control muscles. The relative force output, however, did not differ when corrected for muscle mass. Thus, cachexia significantly reduces absolute skeletal muscle function, but muscle "quality" appears unaltered.

This paper describes the outline and first results of an international study to investigate the effect of a reasonable amount of dietary fish on some aspects of cardiovascular risk. In Maastricht and Zeist, The Netherlands, and Tromsø, Norway, healthy male volunteers were given a dietary supplement consisting of 100 g/d of mackerel or meat for a 6-wk period. Compliance was monitored on the basis of the urinary excretion of lithium, which was added to the supplements. Average compliance was approximately 80% and this decreased slightly in time. Systolic blood pressure decreased in both groups to a comparable degree; consequently no specific effect of the fish supplement was observed. The fish supplement significantly prolonged bleeding times. Hematology was hardly affected but platelet counts decreased significantly. No indications were obtained for adverse effects of the fish supplement.

A single-base deletion in the single-copy vasopressin gene is the cause of diabetes insipidus in the homozygous Brattleboro rat (di/di). It results in the synthesis of an altered vasopressin precursor of which the axonal transport is blocked. Paradoxically, a small number of solitary hypothalamic neurons displays all the immunoreactivities of the wildtype vasopressin precursor (i.e., vasopressin, neurophysin, and a glycopeptide). In the present paper we provide evidence that these neurons have undergone a switch to a genuine heterozygous (di/+) phenotype; i.e., they contain the immunoreactivities of both the wild-type and the mutated vasopressin precursors. In the neural lobe, glycopeptide fibers are also present, showing that axonal transport of the wild-type precursor is restored. Moreover, the number of neurons displaying this di/+ phenotype increases markedly and in a linear way (from 0.1% up to 3% of the vasopressin cells) with age. These findings indicate that after mitotic division has ceased, genomic alterations occur in somatic neurons in vivo. The molecular event generating the di/+ phenotype in the di/di animal could involve a somatic intrachromosomal gene conversion between the homologous exons of the vasopressin and the related oxytocin genes.Since its discovery in 1961 the diabetes insipidus Brattleboro rat (phenotype, di/di) with impaired vasopressin (VP) synthesis has become an extremely useful model for many disciplines to study hypothalamic diabetes insipidus and to clarify problems related to the physiology ofVP (1). The di/di rat exhibits a recessively inherited hypothalamic diabetes insipidus due to a single-base deletion in the unique VP gene (2). This point mutation results in the synthesis of an altered VP precursor whose C-terminal glycopeptide (GP) moiety, because of a frame-shift, is replaced by a nonglycosylated amino acid sequence (2). As a consequence intracellular processing and axonal transport toward the neural lobe ofthe mutant precursor are blocked. Paradoxically, a small number of solitary hypothalamic neurons seems to express wild-type VP gene products that are transported toward the neural lobe (3-5). To explain these results, an intrachromosomal gene conversion between the homologous exons of the VP and oxytocin (OT) genes has been proposed (6). To (termed, di/+) and that the number of these neurons increases linearly with age. The findings imply that genomic alterations occur after mitotic division has ceased and are compatible with the intrachromosomal gene conversion within the VP/OT gene locus. MATERIALS AND METHODSAnimals and Fixation. Male and female di/di Brattleboro rats of 18 days to 79 weeks of age were obtained from Harlan (Zeist, The Netherlands) or homebred. They were individually checked for water consumption and diuresis. The animals were anaesthetized with Nembutal (60 mg/kg, i.p.) and perfused intracardially with 0.9% NaCl (shortly) and then with 0.1 M sodium phosphate-buffered 4% (wt/vol) paraformaldehyde (pH 7.4) and pieces of tissue then wer...

Brown adipose tissue (BAT) undergoes pronounced changes after birth coincident with the loss of the BAT-specific uncoupling protein (UCP)1 and rapid fat growth. The extent to which this adaptation may vary between anatomical locations remains unknown, or whether the process is sensitive to maternal dietary supplementation. We, therefore, conducted a data mining based study on the major fat depots (i.e. epicardial, perirenal, sternal (which possess UCP1 at 7 days), subcutaneous and omental) (that do not possess UCP1) of young sheep during the first month of life. Initially we determined what effect adding 3% canola oil to the maternal diet has on mitochondrial protein abundance in those depots which possessed UCP1. This demonstrated that maternal dietary supplementation delayed the loss of mitochondrial proteins, with the amount of cytochrome C actually being increased. Using machine learning algorithms followed by weighted gene co-expression network analysis, we demonstrated that each depot could be segregated into a unique and concise set of modules containing co-expressed genes involved in adipose function. Finally using lipidomic analysis following the maternal dietary intervention, we confirmed the perirenal depot to be most responsive. These insights point at new research avenues for examining interventions to modulate fat development in early life.