LONGTERM EFFECTS OF PRE-AND POSTNATAL EXPOSURE TO LOW AND HIGH DIETARY PROTEIN LEVELS Evidence From Epidemiological Studies And Controlled Animal Experiments

Abstract: The purpose of this short review is to summarize the available evidence from observational studies and rodent models for an association between maternal protein intake, birth weight, pre-and post-weaning body mass gain and adult body fatness in the offspring

A low protein diet during pregnancy provokes a lasting shift of hepatic expression of genes related to cell cycle throughout ontogenesis in a porcine model

<p>Abstract</p> <p>Background</p> <p>In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. Adverse environmental conditions during fetal development provoke an intrauterine adaptive response termed 'fetal programming', which may lead to both persistently biased responsiveness to extrinsic factors and permanent consequences for the organismal phenotype. This leads to the hypothesis that the offspring's transcriptome exhibits short-term and long-term changes, depending on the maternal diet. In order to contribute to a comprehensive inventory of genes and functional networks that are targets of nutritional programming initiated during fetal life, we applied whole-genome microarrays for expression profiling in a longitudinal experimental design covering prenatal, perinatal, juvenile, and adult ontogenetic stages in a porcine model. Pregnant sows were fed either a gestational low protein diet (LP, 6% CP) or an adequate protein diet (AP, 12% CP). All offspring was nursed by foster sows receiving standard diets. After weaning, all offspring was fed standard diets <it>ad libitum</it>.</p> <p>Results</p> <p>Analyses of the hepatic gene expression of the offspring at prenatal (94 <it>dies post conceptionem</it>, dpc) and postnatal stages (1, 28, 188 <it>dies post natum</it>, dpn) included comparisons between dietary groups within stages as well as comparisons between ontogenetic stages within diets to separate diet-specific transcriptional changes and maturation processes. We observed differential expression of genes related to lipid metabolism (e.g. Fatty acid metabolism, Biosynthesis of steroids, Synthesis and degradation of ketone bodies, FA elongation in mitochondria, Bile acid synthesis) and cell cycle regulation (e.g. Mitotic roles of PLK, G1/S checkpoint regulation, G2/M DNA damage checkpoint regulation). Notably, at stage 1 dpn no regulation of a distinct pathway was found in LP offspring.</p> <p>Conclusions</p> <p>The transcriptomic modulations point to persistent functional demand on the liver towards cell proliferation in the LP group but not in the AP group at identical nutritional conditions during postnatal life due to divergent 'programming' of the genome. Together with the observation that the offspring of both groups did not differ in body weight but in body composition and fat content, the data indicate that the activity of various genes led to diverse partitioning of nutrients among peripheral and visceral organs and tissues.</p

A High Protein Diet during Pregnancy Affects Hepatic Gene Expression of Energy Sensing Pathways along Ontogenesis in a Porcine Model

In rodent models and in humans the impact of gestational diets on the offspring's phenotype was shown experimentally and epidemiologically. The underlying programming of fetal development was shown to be associated with an increased risk of degenerative diseases in adulthood, including the metabolic syndrome. There are clues that diet-dependent modifications of the metabolism during fetal life can persist until adulthood. This leads to the hypothesis that the offspring's transcriptomes show short-term and long-term changes depending on the maternal diet. To this end pregnant German landrace gilts were fed either a high protein diet (HP, 30% CP) or an adequate protein diet (AP, 12% CP) throughout pregnancy. Hepatic transcriptome profiles of the offspring were analyzed at prenatal (94 dpc) and postnatal stages (1, 28, 188 dpn). Depending on the gestational dietary exposure, mRNA expression levels of genes related to energy metabolism, N-metabolism, growth factor signaling pathways, lipid metabolism, nucleic acid metabolism and stress/immune response were affected either in a short-term or in a long-term manner. Gene expression profiles at fetal stage 94 dpc were almost unchanged between the diets. The gestational HP diet affected the hepatic expression profiles at prenatal and postnatal stages. The effects encompassed a modulation of the genome in terms of an altered responsiveness of energy and nutrient sensing pathways. Differential expression of genes related to energy production and nutrient utilization contribute to the maintenance of development and growth performance within physiological norms, however the modulation of these pathways may be accompanied by a predisposition for metabolic disturbances up to adult stages

Milk fatty acids estimated by mid-infrared spectroscopy and milk yield can predict methane emissions in dairy cows

Ruminant enteric methane emission contributes to global warming. Although breeding low methane-emitting cows appears to be possible through genetic selection, doing so requires methane emission quantification by using elaborate instrumentation (respiration chambers, SF6 technique, GreenFeed) not feasible on a large scale. It has been suggested that milk fatty acids are promising markers of methane production. We hypothesized that methane emission can be predicted from the milk fatty acid concentrations determined by mid-infrared spectroscopy, and the integration of energy-corrected milk yield would improve the prediction. Therefore, we examined relationships between methane emission of cows measured in respiration chambers and milk fatty acids, predicted by mid-infrared spectroscopy, to derive diet-specific and general prediction equations based on milk fatty acid concentrations alone and with the additional consideration of energy-corrected milk yield. Cows were fed diets differing in forage type and linseed supplementation to generate a large variation in both CH4 emission and milk fatty acids. Depending on the diet, equations derived from regression analysis explained 61 to 96% of variation of methane emission, implying the potential of milk fatty acid data predicted by mid-infrared spectroscopy as novel proxy for direct methane emission measurements. When data from all diets were analyzed collectively, the equation with energy-corrected milk yield (CH4 (L/day) = − 1364 + 9.58 × energy-corrected milk yield + 18.5 × saturated fatty acids + 32.4 × C18:0) showed an improved coefficient of determination of cross-validation R2 CV = 0.72 compared to an equation without energy-corrected milk yield (R2 CV = 0.61). Equations developed for diets supplemented by linseed showed a lower R2 CV as compared to diets without linseed (0.39 to 0.58 vs. 0.50 to 0.91). We demonstrate for the first time that milk fatty acid concentrations predicted by mid-infrared spectroscopy together with energy-corrected milk yield can be used to estimate enteric methane emission in dairy cows. © 2018, The Author(s)

Effect of oral glutamine supplementation on growth and glutamine and glucose metabolism in suckling piglets

The increase in litter size has led to a higher proportion of low birthweight (LBW) piglets, which are disadvantaged in terms of later growth and organ maturation. Supplementing with glutamine (Gln) has been proposed to improve this situation. We investigated the metabolism of Gln and glucose (Glc) in LBW and normal (NBW) birthweight (BiW) suckling piglets supplemented with Gln or water (W). Forty-six neonatal male German Landrace piglets with a BiW of 1.04 ± 0.02 kg for LBW piglets and 1.55 ± 0.02 kg for NBW piglets were assigned to one of four treatments in a 2 × 2 factorial design (LBW/NBW; Gln/W). Half of the groups received either 1 g/kg bodyweight (BW)/d of Gln (LBW-Gln, NBW-Gln; n = 12) dissolved in water, or water (W) as a control (LBW-W, NBW-W; n = 11), until age 15 d. At 12 d, piglets were implanted a jugular vein catheter and then underwent oral tests: on 14 d with 13C5-Gln/Gln, on 15 d with lactulose/mannitol (Lac/Man) and on 16 d with 13C6-Glc/Glc and xylose (Xyl). After a baseline blood sample, blood samples were collected over 5 h. Enrichments of 13C tracers in plasma and 13CO2 in red blood cells (RBC) were measured, along with plasma concentrations of Lac, Man, Xyl, Glc, lactate, urea, and amino acids. We calculated plasma Gln and Glc rate of appearance (Ra), 13C recovery (13C REC) in RBC CO2 from 13C5-Gln and 13C6-Glc as a proxy of whole-body oxidation and 13C6-Gln conversion to 13C3-Glc to obtain a measure of gluconeogenesis. The BW, average daily gain (ADG), abdominal circumference (ABC), crown-rump length (CRL), body mass index (BMI), and ponderal index were measured. The BW of LBW piglets supplemented with Gln was lower than of those supplemented with W at 12, 13, and 15 d (P  0.1). In conclusion, LBW and NBW piglets differ in Gln and Glc metabolism, but Gln supplementation did not show a consistent effect on the measured parameters

Effects of Oral Glutamine Supplementation, Birthweight and Age on Colonic Morphology and Microbiome Development in Male Suckling Piglets

Mortality, impaired development and metabolic dysfunctions of suckling low-birthweight piglets may be influenced by modulating the intestinal microbiome through glutamine supplementation. Therefore, this study examined whether glutamine supplementation may affect the colonic development and microbiome composition of male low- and normal-birthweight piglets at 5 and 12 days of age. Suckling piglets were supplemented orally with glutamine or alanine. Colonic digesta samples were obtained for 16S rDNA sequencing, determination of bacterial metabolites and histomorphological tissue analyses. Glutamine-supplemented piglets had lower concentrations of cadaverine and spermidine in the colonic digesta (p < 0.05) and a higher number of CD3+ colonic intraepithelial lymphocytes compared to alanine-supplemented piglets (p < 0.05). Low-birthweight piglets were characterised by a lower relative abundance of Firmicutes, the genera Negativibacillus and Faecalibacterium and a higher abundance of Alistipes (p < 0.05). Concentrations of cadaverine and total biogenic amines (p < 0.05) and CD3+ intraepithelial lymphocytes (p < 0.05) were lower in low- compared with normal-birthweight piglets. In comparison to the factor age, glutamine supplementation and birthweight were associated with minor changes in microbial and histological characteristics of the colon, indicating that ontogenetic factors play a more important role in intestinal development

Methane prediction based on individual or groups of milk fatty acids for dairy cows fed rations with or without linseed

Milk fatty acids (MFA) are a proxy for the prediction of CH4 emission from cows, and prediction differs with diet. Our objectives were (1) to compare the effect of diets on the relation between MFA profile and measured CH4 production, (2) to predict CH4 production based on 6 data sets differing in the number and type of MFA, and (3) to test whether additional inclusion of energy-corrected milk (ECM) yield or dry matter intake (DMI) as explanatory variables improves predictions. Twenty dairy cows were used. Four diets were used based on corn silage (CS) or grass silage (GS) without (L0) or with linseed (LS) supplementation. Ten cows were fed CS-L0 and CS-LS and the other 10 cows were fed GS-L0 and GS-LS in random order. In feeding wk 5 of each diet, CH4 production (L/d) was measured in respiration chambers for 48 h and milk was analyzed for MFA concentrations by gas chromatography. Specific CH4 prediction equations were obtained for L0-, LS-, GS-, and CS-based diets and for all 4 diets collectively and validated by an internal cross-validation. Models were developed containing either 43 identified MFA or a reduced set of 7 groups of biochemically related MFA plus C16:0 and C18:0. The CS and LS diets reduced CH4 production compared with GS and L0 diets, respectively. Methane yield (L/kg of DMI) reduction by LS was higher with CS than GS diets. The concentrations of C18:1 trans and n-3 MFA differed among GS and CS diets. The LS diets resulted in a higher proportion of unsaturated MFA at the expense of saturated MFA. When using the data set of 43 individual MFA to predict CH4 production (L/d), the cross-validation coefficient of determination (R2 CV) ranged from 0.47 to 0.92. When using groups of MFA variables, the R2 CV ranged from 0.31 to 0.84. The fit parameters of the latter models were improved by inclusion of ECM or DMI, but not when added to the data set of 43 MFA for all diets pooled. Models based on GS diets always had a lower prediction potential (R2 CV = 0.31 to 0.71) compared with data from CS diets (R2 CV = 0.56 to 0.92). Models based on LS diets produced lower prediction with data sets with reduced MFA variables (R2 CV = 0.62 to 0.68) compared with L0 diets (R2 CV = 0.67 to 0.80). The MFA C18:1 cis-9 and C24:0 and the monounsaturated FA occurred most often in models. In conclusion, models with a reduced number of MFA variables and ECM or DMI are suitable for CH4 prediction, and CH4 prediction equations based on diets containing linseed resulted in lower prediction accuracy. © 2019 American Dairy Science Associatio

Acute and persistent effects of oral glutamine supplementation on growth, cellular proliferation, and tight junction protein transcript abundance in jejunal tissue of low and normal birthweight pre-weaning piglets

Breeding for higher fertility has resulted in a higher number of low birthweight (LBW) piglets. It has been shown that LBW piglets grow slower than normal birthweight (NBW) littermates. Differences in growth performance have been associated with impaired small intestinal development. In suckling and weaning piglets, glutamine (Gln) supplementation has been associated with improved growth and intestinal development. This study was designed to examine the effects of oral Gln supplementation on growth and small intestinal parameters in LBW and NBW suckling piglets. At birth (day 0), a total of 72 LBW (1.10 ± 0.06 kg) and 72 NBW (1.51 ± 0.06) male piglets were selected. At day 1, litters were standardized to 12 piglets, and experimental piglets supplemented daily with either Gln (1 g/kg BW) or isonitrogenous amounts of Alanine (Ala) as control (1.22 g/kg BW) until day 12. Creep feed was offered from day 14 onward. Subgroups of piglets were euthanized at days 5, 12, and 26 for the analyses of jejunal morphometry, cellular proliferation, glutathione concentration and transcript abundance of tight junction proteins. From age day 11 to 21, Gln supplemented LBW (LBW-Gln) piglets were heavier than Ala supplemented LBW (LBW-Ala) littermates (P = 0.034), while NBW piglets were heavier until age day 26 compared to LBW littermates. Villus height was higher in LBW-Gln compared to LBW-Ala on age day 12 (P = 0.031). Sporadic differences among supplementation and birthweight groups were detected for jejunal cellular proliferation, cellular population and glutathione concentration, whereas age was the most dominant factor. These results show that Gln supplementation improved the growth of LBW piglets compared to LBW-Ala beyond the termination of Gln supplementation, but this was not associated with consistent effects on selected parameters of jejunal development

Glutamine supplementation moderately affects growth, plasma metabolite and free amino acid patterns in neonatal low birth weight piglets

Low birth weight (LBW) neonates show impaired growth compared with normal birth weight (NBW) neonates. Glutamine (Gln) supplementation benefits growth of weaning piglets, while the effect on neonates is not sufficiently clear. We examined the effect of neonatal Gln supplementation on piglet growth, milk intake and metabolic parameters. Sow-reared pairs of newborn LBW (0·8–1·2 kg) and NBW (1·4–1·8 kg) male piglets received Gln (1 g/kg body mass (BM)/d; Gln-LBW, Gln-NBW; n 24/group) or isonitrogenous alanine (1·22 g/kg BM/d; Ala-LBW; Ala-NBW; n 24/group) supplementation at 1–5 or 1–12 d of age (daily in three equal portions at 07:00, 12:00 and 17:00 by syringe feeding). We measured piglet BM, milk intake (1, 11–12 d), plasma metabolite, insulin, amino acid (AA) and liver TAG concentrations (5, 12 d). The Gln-LBW group had higher BM (+7·5%, 10 d, P = 0·066; 11–12 d, P < 0·05) and milk intake (+14·7%, P = 0·015) than Ala-LBW. At 5 d, Ala-LBW group had higher plasma TAG (+34·7%, P < 0·1) and lower carnosine (–22·5%, P < 0·05) than Ala-NBW and Gln-LBW, and higher liver TAG (+66·9%, P = 0·029) than Ala-NBW. At 12 d, plasma urea was higher (+37·5%, P < 0·05) with Gln than Ala supplementation. Several proteinogenic AA in plasma were lower (P < 0·05) in Ala-NBW v. Gln-NBW. Plasma arginine was higher (P < 0·05) in Gln-NBW v Ala-NBW piglets (5, 12 d). Supplemental Gln moderately improved growth and milk intake and affected lipid metabolism in LBW piglets and AA metabolism in NBW piglets, suggesting effects on intestinal and liver function

Measurement of Oro-Cecal Transit Time in LPS-Treated Pigs Fed High and Low Fiber Diets Using the Lactose-13C-Ureide Test in Breath and Saliva Samples

The lactose-13C-ureide (L13CU) test, used in humans to measure oro-cecal transit time (OCTT) in breath CO2, was assessed for its suitability in pigs as a noninvasive alternative to intestinal cannulation. The OCTT was determined with the L13CU test in breath and saliva samples when pigs were fed low or high dietary fiber (DF) (low fiber, 2.8% DF; high fiber 6.5% DF) diets, and 24 h after an i.m. injection with either lipopolysaccharide (LPS) or NaCl. The OCTT measured in breath was longer in LF-LPS than in LF-NaCl and HF-LPS groups (3.4 vs 2.9 h; p < 0.05). Additionally, LPS prolonged the OCTT of pigs, and DF prevented this effect. 90 % of OCTT estimates measured in saliva and breath CO2 did not differ. We conclude that the L13CU breath test is useful for determining OCTT in pigs; saliva is generally suitable as a sample matrix for OCTT, but its use requires further validation