Current Protein and Peptide Science - Volume 20, Issue 7, 2019

Branched chain amino acids are the essential nutrients for humans and many animals. As functional amino acids, they play important roles in physiological functions, including immune functions. Isoleucine, as one of the branched chain amino acids, is also critical in physiological functions of the whole body, such as growth, immunity, protein metabolism, fatty acid metabolism and glucose transportation. Isoleucine can improve the immune system, including immune organs, cells and reactive substances. Recent studies have also shown that isoleucine may induce the expression of host defense peptides (i.e., β-defensins) that can regulate host innate and adaptive immunity. In addition, isoleucine administration can restore the effect of some pathogens on the health of humans and animals via increasing the expression of β-defensins. Therefore, the present review will emphatically discuss the effect of isoleucine on immunity while summarizing the relationship between branched chain amino acids and immune functions.

The intestinal epithelial barrier plays a crucial role in the health and growth of weaned piglets. Proper epithelial function mainly depends on tight junctions (TJs), which act as both ion channels and a barrier against noxious molecules. TJs are multiprotein complexes consisting of transmembrane and membrane-associated proteins. Because the intestine in piglets is immature and incomplete, its structure and function are easily impaired by various stresses, infections, and food-related factors. Certain nutrients have been demonstrated to participate in intestinal TJ regulation. Probiotics, amino acids, fibers, oligosaccharide, and certain micronutrients can enhance barrier integrity and counteract infections through elevated TJ protein expression and distribution. In this review, the distribution and classification of intestinal TJs is described, the factors influencing TJs after weaning are summarized, and the regulation of weaning piglet intestinal TJs by nutrients is discussed.

As a major component of biologically active compounds in the body, proteins contribute to the synthesis of body tissues for the renewal and growth of the body. The high level of dietary protein and the imbalance of amino acid (AA) composition in mammals result in metabolic disorders, inefficient utilization of protein resources and increased nitrogen excretion. Fortunately, nutritional interventions can be an effective way of attenuating the nitrogen excretion and increasing protein utilization, which include, but are not limited to, formulating the AA balance and protein-restricted diet supplementing with essential AAs, and adding probiotics in the diet. This review highlights recent advances in the turnover of dietary proteins and mammal’s metabolism for health, in order to improve protein bioavailability through nutritional approach.

The rapid self-renewal of intestinal epithelial cells enhances intestinal function, promotes the nutritional needs of animals and strengthens intestinal barrier function to resist the invasion of foreign pathogens. MicroRNAs (miRNAs) are a class of short-chain, non-coding RNAs that regulate stem cell proliferation and differentiation by down-regulating hundreds of conserved target genes after transcription via seed pairing to the 3' untranslated regions. Numerous studies have shown that miRNAs can improve intestinal function by participating in the proliferation and differentiation of different cell populations in the intestine. In addition, miRNAs also contribute to disease regulation and therefore not only play a vital role in the gastrointestinal disease management but also act as blood or tissue biomarkers of disease. As changes to the levels of miRNAs can change cell fates, miRNA-mediated gene regulation can be used to update therapeutic strategies and approaches to disease treatment.

Intestines are not only major organs for nutrient digestion and absorption, but are also the largest immune organ in pigs. They are essential for maintaining the health and growth of piglets. Fatty acids, including short-chain fatty acids, medium-chain fatty acids, and long-chain polyunsaturated fatty acids, are important nutrients; they are a major energy source, important components of the cell membrane, metabolic substrates in many biochemical pathways, cell-signaling molecules, and play role as immune modulators. Research has shown that fatty acids exert beneficial effects on intestinal health in animal models and clinical trials. The objective of this review is to give a clear understanding of the regulatory effects of fatty acids of different chain lengths on intestinal health in pigs and their signaling pathways, providing scientific reference for developing a feeding technique to apply fatty acids to piglet diets.

Weaning is a critical period for the growth and development of mammals, in which various physiological and biochemical indicators of the body have undergone great changes. The development, differentiation, and maturation of the nervous system are regulated by many proteins. Changes in related proteins affect the physiological functions of the nervous system. However, the regulation of selfrenewal and differentiation of the nervous system at this stage is still poorly understood. The mechanism of differentiation and regulation of the major proteins in the nervous system during this special period of weaning remains to be investigated. Therefore, this paper aims to summarize the alteration of the nervous system during weaning and provide the basis for subsequent research.

Weaning is a stressful event associated with gastrointestinal disorders and increased disease susceptibility. Many studies have reported the changes that happened in the gut of various mammals such as pigs and rats after weaning. These findings suggest that the development of intestinal tract mainly is affected at the time of weaning through interfering in the differentiation and proliferation of intestinal stem cells. Weaning stress stimulates the rapid differentiation and proliferation of intestinal stem cells in order to adjust to changes caused by weaning, which are mainly manifested as deeper crypt depth and decreased intestine villus height. However, the accelerated cellular process may lead to an increase in the proportion of immature intestinal epithelial cells and goblet cells, which affect intestinal permeability and reduce the gut-barrier function against toxins and pathogens. This review briefly describes the effects coforticotrophin-releasing factor (CRF), epidermal growth factor (EGF) and polyamines on the differentiation and proliferation of intestinal stem cells after weaning and discusses its possible underlying regulatory mechanisms. Firstly, weaning stress activates CRF to binds its receptors, which induces proinflammatory responses and promote rapid differentiation and proliferation of intestinal stem cells to a larger fraction of immature intestinal epithelial cells and goblet cells. Secondly, the lack of EGF after weaning inhibits the expression of goblet cell maturation factors and makes it difficult for goblet cells and intestinal epithelial cells to mature. Finally, diet and endogenous synthesis lead to excessive polyamines in the intestine, which promote the proliferation of intestinal stem cells by regulating the expression of human antigen R (HuR) and other related genes at the time of weaning.

Numerous experimental studies have demonstrated that a series of remodeling processes occurred in the adipose tissue during the weaning, such as differentiation. Fibroblasts in the breast at weaning stage could re-differentiate into mature adipocytes. Many transcriptional factors were involved in these processes, especially the PPARγ, C/EBP, and SREBP1. There is cell apoptosis participating in the breast tissue degeneration and secretory epithelial cells loss during weaning. In addition, hormones, especially the estrogen and pituitary hormone, play a vital role in the whole reproductive processes. In this review, we mainly focus on the underlying regulated mechanisms of differentiation of adipose tissue and apoptosis of breast cell to provide a specific insight into the physiological changes during weaning.

Lactation is a critical phase for brain function development. New dietary experiences of mouse caused by weaning can regulate brain development and function, increase their response to food and environment, and eventually give rise to corresponding behavioral changes. Changes in weaning time induce the alteration of brain tissues morphology and molecular characteristics, glial cell activity and behaviors in the offspring. In addition, it is also sensitive to the intervention of environment and drugs during this period. That is to say, the study focused on brain development and function based on mouse weaning is critical to demonstrate the underlying pathogenesis of neuropsychiatric diseases and find new drug targets. This article mainly focuses on the developmental differentiation of the brain during lactation, especially during weaning in mice.

Intrauterine growth restriction (IUGR) remains a major problem in swine production since the associated low birth weight leads to high rates of pre-weaning morbidity and mortality, and permanent retardation of growth and development. The underlying regulatory mechanisms from the aspects of epigenetic modification has received widespread attention. Studies explore the changes in genome wide methylation in small intestine (SI), liver and longissimus dorsi muscle (LDM) between IUGR and normal birth weight (NBW) newborn piglets using a methylated DNA immunoprecipitation-sequencing (MeDIP-Seq) approach. The data demonstrated that methylated peaks were prominently distributed in distal intergenic regions and the quantities of peaks in IUGR piglets were more than that of NBW piglets. IUGR piglets had relatively high methylated level in promoters, introns and coding exons in all the three tissues. Through KEGG pathway analysis of differentially methylated genes found that 33, 54 and 5 differentially methylated genes in small intestine, liver and longissimus dorsi muscle between NBW and IUGR piglets, respectively, which are related to development and differentiation, carbohydrate and energy metabolism, lipid metabolism, protein turnover, immune response, detoxification, oxidative stress and apoptosis pathway. The objective of this review is to assess the impact of differentially methylation status on developmental delay, metabolic disorders and immune deficiency of IUGR piglets.

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.

Weaned piglets experience sudden changes in their dietary patterns such as withdrawal from the easily digestible watery milk to a coarse cereal diet with both systemic and intestinal disruptions coupling with the expression of pro-inflammatory proteins which affects the immune system and the concentrations of haptoglobin including both positive and negative acute-phase proteins in the plasma. L-arginine is an important protein amino acid for piglets, but its inadequate synthesis is a nutritional problem for both sows and piglets. Recent studies indicated that dietary supplementation of L-arginine increased feed intake, uterine growth, placental growth and nutrient transport, maternal growth and health, embryonic survival, piglets birth weight, piglet’s growth, and productivity, and decreased stillbirths. L-arginine is essential in several important pathways involved in the growth and development of piglets such as nitric oxide synthesis, energy metabolism, polyamine synthesis, cellular protein production and muscle accretion, and the synthesis of other functional amino acids. However, the underlying molecular mechanism in these key pathways remains largely unresolved. This review was conducted on the general hypothesis that L-arginine increased the growth and survival of post-weaning piglets. We discussed the effects of dietary L-arginine supplementation during gestation, parturition, lactation, weaning, and post-weaning in pigs as each of these stages influences the health and survival of sows and their progenies. Therefore, the aim of this review was to discuss through a logical approach the effects of L-arginine supplementation on piglet’s growth and survival from conception to postweaning.

Obesity is one of the main challenges of public health in the 21st century. Obesity can induce a series of chronic metabolic diseases, such as diabetes, dyslipidemia, hypertension and nonalcoholic fatty liver, which seriously affect human health. Gut-brain axis, the two-direction pathway formed between enteric nervous system and central nervous system, plays a vital role in the occurrence and development of obesity. Gastrointestinal signals are projected through the gut-brain axis to nervous system, and respond to various gastrointestinal stimulation. The central nervous system regulates visceral activity through the gut-brain axis. Brain-gut peptides have important regulatory roles in the gut-brain axis. The brain-gut peptides of the gastrointestinal system and the nervous system regulate the gastrointestinal movement, feeling, secretion, absorption and other complex functions through endocrine, neurosecretion and paracrine to secrete peptides. Both neuropeptide Y and peptide YY belong to the pancreatic polypeptide family and are important brain-gut peptides. Neuropeptide Y and peptide YY have functions that are closely related to appetite regulation and obesity formation. This review describes the role of the gutbrain axis in regulating appetite and maintaining energy balance, and the functions of brain-gut peptides neuropeptide Y and peptide YY in obesity. The relationship between NPY and PYY and the interaction between the NPY-PYY signaling with the gut microbiota are also described in this review.

Milk is the basic food for infants and newborn animals, providing a rich source of proteins, carbohydrates, minerals, and vitamins. Milk also provides nourishment for people of all ages due to its abundant nutrients, and it is used in the manufacture of numerous health-related products. Milk contains caseins and whey proteins as the two major protein classes. Caseins fall into four major types known as αs1-, αs2-, β- and Κ-casein, whereas whey proteins comprise a mixture of globular proteins including β-lactoglobulin, α-lactalbumin, serum albumin, lactoferrin, and other bioactivators. The various biological activities of these proteins are involved in preventing and treating numerous nutritional, physiological and metabolic diseases. This article reviews the bioactivities and functions of milk proteins, which may shed light on future application of milk bioactive substances.