Restricted Ion Research Articles

Role of AMPK signalling pathway during compensatory growth in pigs

BackgroundThe molecular basis of compensatory growth in monogastric animals has not yet been fully explored. Herewith, in this study we aim to determine changes in the pig skeletal muscle transcriptome profile during compensatory growth following a feed restriction period. A RNA-Seq experiment was performed with a total of 24 females belonging to a Duroc commercial line. Half of the animals received either a restricted (RE) or ad libitum (AL) diet during the first fattening period (60–125 d of age). After that, all gilts were fed ad libitum for a further ~30 d until the age of ~155 d, when animals were slaughtered and samples of gluteus medius muscle were harvested to perform RNA-Seq analyses and intramuscular fat content determination.ResultsDuring the period following food restriction, RE animals re-fed ad libitum displayed compensatory growth, showed better feed conversion rate and tended to deposit more subcutaneous fat than AL fed animals. Animals were slaughtered in the phase of accelerated growth, when RE animals had not completely compensated the performance of AL group, showing lower live and carcass weights. At intramuscular level, RE gilts showed a higher content of polyunsaturated fatty acids during the compensatory growth phase. The comparison of RE and AL expression profiles allowed the identification of 86 (ǀlog2Fold-Changeǀ > 1, padj < 0.05) differentially expressed (DE) genes. A functional categorization of these DE genes identified AMPK Signaling as the most significantly enriched canonical pathway. This kinase plays a key role in the maintenance of energy homeostasis as well as in the activation of autophagy. Among the DE genes identified as components of AMPK Signaling pathway, five out of six genes were downregulated in RE pigs.ConclusionsAnimals re-fed after a restriction period exhibited a less oxidative metabolic profile and catabolic processes in muscle than animals fed ad libitum. The downregulation of autophagy observed in the skeletal muscle of pigs undergoing compensatory growth may constitute a mechanism to increase muscle mass thus ensuring an accelerated growth rate. These results reveal that the downregulation of AMPK Signaling plays an important role in compensatory growth in pigs.

The Effect of the Bariatric Surgery Type on the Levothyroxine Dose of Morbidly Obese Hypothyroid Patients.

Doubts exist about the effect of different bariatric surgery (BS) types on levothyroxine (Lt4) absorption. We compared Lt4 doses and their variation (ΔLt4) in patients with hypothyroidism that underwent malabsorptive (MS) or restrictive (RS) surgery and studied predictors of Lt4 dose change. Retrospective study of morbidly obese hypothyroid patients submitted to BS. We compared RS ("sleeve" gastrectomy or adjustable gastric banding) with MS (Roux-en-Y gastric bypass) patients. We built a multivariable logistic regression and a linear regression model to study predictors of Lt4 dose changes and ΔLt4, respectively. Fifty-seven patients: 35 MS and 22 RS. Mean age 47years; 7% men. Patients submitted to MS had lower BMI at 1year than those submitted to RS. Lt4 dose remained unchanged in 61.4%, increased in 12.3%, and decreased in 26.3% of patients. Initial and 1-year Lt4 dose were not different between surgical groups. Relative Lt4 dose, but not absolute (p = 0.07), increased at 1year (p < 0.001). Neither BS nor BMI variation were predictors of Lt4 dose variation. BMI variation was associated with relative Lt4 dose change independently of initial BMI and BS type: β (95%CI) - 0.03 (- 0.05; 0.00); p = 0.03. There were no differences in Lt4 dose and its variation between restrictive and malabsorptive techniques 1year after surgery. Malabsorptive procedures may not affect Lt4 absorption differently from restrictive ones. Bariatric surgery type was not predictive of Lt4 dose changes. BMI variation is associated with relative Lt4 dose (dose per weight) variation and its association was independent of bariatric surgery type.

Early feed restriction of lambs modifies ileal epimural microbiota and affects immunity parameters during the fattening period

Bacteria firmly attached to the gastrointestinal epithelium during the pre-weaning phase may show a significant impact on nutrient processing, immunity parameters, health and feed efficiency of lambs during post-weaning phases. Thus, the aim of this study was to describe the differences in the ileal epimural microbiota (e.g. total bacteria, Prevotella spp., Bifidobacterium spp. and Lactobacillus spp.) of fattening lambs promoted by early feed restriction during the suckling phase trying to elucidate some of the underlying mechanisms behind changes in feed efficiency during the fattening period. A total of 24 Merino lambs (average BW 4.81±0.256 kg) were used, 12 of them (ad libitum, ADL) kept permanently in individual pens with their mothers, whereas the other 12 lambs were separated from their dams for 9 h each day to be exposed to milk restriction (RES). After weaning (BW=15 kg) all the animals were penned individually, offered the same complete pelleted diet (35 g/kg BW per day) and slaughtered at a BW of 27 kg. During the fattening period, reduced gain : feed ratio (0.320 v. 0.261, P<0.001) was observed for the RES group. Moreover, increments of Prevotella spp. were detected in the ileal epimural microbiota of RES lambs (P<0.05). There were also higher numbers of infiltrated lymphocytes (T and B cells) in the ileal lamina propria (P<0.05), a higher M-cell labelling intensity in ileal Peyer’s patches domes (P<0.05) and a trend towards a thickening of the submucosa layer when compared with the ADL group (P=0.057). Some other immunological parameters, such as an increased immunoglobulin A (IgA) production (pg IgA/µg total protein) and increments in CD45+ cells were also observed in the ileum of RES group (P<0.05), whereas transforming growth factor β and toll-like receptor gene expression was reduced (P<0.05). In conclusion, early feed restriction during the suckling phase promoted changes in ileal epimural microbiota and several immunity parameters that could be related to differences in feed efficiency traits during the fattening period of Merino lambs.

Feed efficiency and the liver proteome of fattening lambs are modified by feed restriction during the suckling period

The present study was designed to describe the effects of early feed restriction of Merino lambs on feed efficiency during the fattening period by examining ruminal microbiota and fermentation parameters, gastrointestinal morphology, digestibility or liver proteome. In total, 24 male Merino lambs were randomly assigned to two experimental treatments (n=12 per treatment). Lambs of the first group (ad libitum (ADL)) were kept permanently with the dams, whereas the other 12 lambs (restricted (RES)) were milk restricted. When lambs reached a live BW (LBW) of 15 kg, all the animals were offered the same complete pelleted diet (35 g dry matter/kg LBW per day) until slaughter at a LBW of 27 kg. The RES lambs showed poorer feed efficiency during the fattening period when compared with the ADL group (feed to gain ratio, 3.69 v. 3.05, P<0.001). No differences were observed in ruminal microbiota, fermentation parameters or apparent digestibility. However, the proportion of the small intestine and the length of ileal villi were reduced in the RES lambs. In total, 26 spots/proteins were identified in the liver proteomic profile, with significant differences (P<0.05) between experimental treatments, suggesting a higher catabolism of proteins and a reduction in β-oxidation of fatty acids in RES lambs when compared with the ADL animals. In conclusion, early feed restriction of Merino lambs during the suckling period promotes long-term effects on the small intestine and the proteomic profile of the liver, which may influence the metabolic use of nutrients, thus negatively affecting feed efficiency during the fattening phase.

The effect of energy restriction on fatty acid profiles of longissimus dorsi and tissue adipose depots in sheep1

Sheep production systems in northwest China depend mostly on natural grasslands. Seasonal growth and maturity fluctuations can cause periodical restrictions in food quality and quantity. These fluctuations, in turn, result in variability in fat deposition and fatty acid profiles in different fat depots. Consequently, the study objective was to compare fat deposition, intramuscular fat (IMF) percentage and fatty acid profiles of the longissimus dorsi (LD), kidney fat (KF), tail fat (TF), and subcutaneous fat (SF) in lambs under ME restrictions similar to seasonal changes observed in the natural grasslands of northwest China. Nineteen male Dorper × Small Tailed Han lambs were assigned to 2 treatments, a control (CON) fed at 1.0 MJ / W × d and restricted (RES) by restricting ME sequentially every 30 d (0.56 MJ / W × d, 0.84 / W × d, 1.0 MJ / W × d, 0.84 MJ / W × d, 0.56 MJ / W × d, 0.28 MJ / W × d). All lambs were harvested at the end of the 180 d experimental period. Compared to CON fed lambs, restricting ME resulted in lesser IMF, fat deposition indexes ( < 0.05) except testicular and heart fat and greater ( < 0.05) SFA in LD, KF, and TF depots. The RES fed lambs had greater ( < 0.05) -3 PUFA, eicosatrienoic acid (C20:3n3), eicosapentaenoic acid (C20:5n3, EPA), and trans-linolelaidic acid (C18:2n6t) in LD muscle. The conjugated linoleic acids (CLA) content was greater in the SF depots of the CON fed lambs compared to the RES fed lambs. Fatty acid ratios (unsaturated fatty acid; USFA:SFA, MUFA:SFA, PUFA:SFA), and percentage USFA in RES fed lambs were lesser in muscle and adipose tissue compared to CON fed lambs ( < 0.05), except SF depots. In RES fed lambs, EFA were less ( < 0.05) in LD and KF depots and the ratios of functional fatty acids were lesser in LD and some adipose tissues ( < 0.05), including lesser n-6:n-3 in KF and SF ( < 0.05) depots, lesser USFA, SFA, MUFA, SFA in LD, KF, and TF ( < 0.05) depots, and lesser PUFA and SFA in LD and TF ( < 0.05) depots. Results from this research demonstrate that sequential energy restriction, as might be experience during seasonal forage quality and quantity changes in natural grasslands, result in lesser intramuscular fat with associated lesser quality, as well as, changes in fatty acid composition in different fat depots, which has implications for both meat quality and animal physiological functions.

Reducing mineral usage in feedlot diets for Nellore cattle: I. Impacts of calcium, phosphorus, copper, manganese, and zinc contents on microbial efficiency and ruminal, intestinal, and total digestibility of dietary constituents.

This study evaluated intake, microbial efficiency, and ruminal, small and large intestinal, and total digestibility of DM, OM, CP, and NDF, as well as availability of Ca, P, Mg, Na, K, Cu, Mn, and Zn in Zebu cattle fed with or without supplemental sources of Ca and P or a micromineral premix. Five rumen- and ileum-cannulated Nellore bulls (BW = 200 ± 10.5 kg; 9 mo) were used in the experiment, distributed in a 5 × 5 Latin square design. The experiment was developed in a 2 × 2 + 1 factorial design to measure the effects of mineral supplementation on intake, digestibility, and site of nutrient absorption. The factors consisted of 2 Ca and P levels (macromineral factor; CaP+ or CaP-) and 2 microminerals levels (micromineral factor; CuMnZn+ or CuMnZn-). In addition, a treatment with alimentary restriction (REST) was evaluated at 1.7% of BW. Nutrient fluxes were measured in the omasum and ileum, in addition to intake and fecal excretion. Microbial efficiency was estimated using purine derivative excretion. Dry matter, OM, NDF, CP intake, and total digestibility were not affected ( ≥ 0.058) by the absence of Ca, P, Cu, Mn, and Zn supplementation. Intake of Ca, P, and Mg were reduced ( < 0.01) by CaP-. The absence of CuMnZn reduced ( < 0.01) Cu, Mn, and Zn intake. Ruminal recycling of P, Na, and K is significant for increasing the influx of these minerals to the digestive tract; however, influences of treatments were not observed. The small and large intestines contributed to mineral absorption in different proportions ( < 0.05), according to minerals and treatments. Because of the similarity ( > 0.05) of OM, NDF, and CP digestion sites and coefficients, we assume that omitting supplemental sources of Ca, P, Cu, Mn, and Zn may be an option in raising cattle on feedlots. If supplementation is viable, knowledge about the specific absorption site of each mineral could positively impact choices about the supplemental source.

Evaluation of soil intake by growing Creole young bulls in common grazing systems in humid tropical conditions

Soil is the main matrix which contributes to the transfer of environmental pollutants to animals and consequently into the food chain. In the French West Indies, chlordecone, a very persistent organochlorine pesticide, has been widely used on banana growing areas and this process has resulted in a long-term pollution of the corresponding soils. Domestic outside-reared herbivores are exposed to involuntary soil intake, and tethered grazing commonly used in West Indian systems can potentially favour their exposure to chlordecone. Thus, it appears necessary to quantify to what extent grazing conditions will influence soil intake. This experiment consisted of a cross-over design with two daily herbage allowance (DHA) grazed alternatively. Six young Creole bulls were distributed into two groups (G1 and G2) according to their BW. The animals were individually tethered and grazed on a restrictive (RES) or non-restrictive (NRES) levels of DHA during two successive 10-days periods. Each bull progressed on a new circular area every day. The two contrasting levels of DHA (P<0.001) were obtained via a different daily grazing surface area (RES: 20 m2/animal, NRES: 31 m2/animal; P<0.01) offered to the animals by the modulation of the length of the tethering chain (RES: 1.9 m, NRES: 2.6 m). These differences in offered grazing areas resulted in DHA of 71 and 128 g DM/kg BW0.75, respectively for RES and NRES treatments. As expected, the animals grazing on the reduced area realized a lower daily dry matter intake (DMI) (RES: 1.12 kg/100 kg BW, NRES: 1.83 kg/100 kg BW; P<0.05) and present a lower organic matter digestibility (RES: 0.67, NRES: 0.73; P<0.01) than NRES ones, due in part to the shorter post-grazing sward surface height (RES: 3.3 cm, NRES: 5.2 cm; P<0.01) of their grazing circles. Soil intake was estimated on an individual level based on the ratio of the marker titanium in soil, herbage and faeces. Grazing closer to the ground, animals on RES treatment ingested a significantly higher proportion of soil in their total DMI (RES: 9.3%, NRES: 4.4%; P<0.01). The amount of ingested soil in the diet was not significantly different between the two treatments (RES: 98 g/100 kg BW, NRES: 78 g/100 kg BW; P>0.05) due to the lower DMI of RES compared with NRES treatment.

The effect of energy restriction on fatty acid profiles of longissimus dorsi and tissue adipose depots in sheep.

Sheep production systems in northwest China depend mostly on natural grasslands. Seasonal growth and maturity fluctuations can cause periodical restrictions in food quality and quantity. These fluctuations, in turn, result in variability in fat deposition and fatty acid profiles in different fat depots. Consequently, the study objective was to compare fat deposition, intramuscular fat (IMF) percentage and fatty acid profiles of the longissimus dorsi (LD), kidney fat (KF), tail fat (TF), and subcutaneous fat (SF) in lambs under ME restrictions similar to seasonal changes observed in the natural grasslands of northwest China. Nineteen male Dorper × Small Tailed Han lambs were assigned to 2 treatments, a control (CON) fed at 1.0 MJ / W × d and restricted (RES) by restricting ME sequentially every 30 d (0.56 MJ / W × d, 0.84 / W × d, 1.0 MJ / W × d, 0.84 MJ / W × d, 0.56 MJ / W × d, 0.28 MJ / W × d). All lambs were harvested at the end of the 180 d experimental period. Compared to CON fed lambs, restricting ME resulted in lesser IMF, fat deposition indexes ( < 0.05) except testicular and heart fat and greater ( < 0.05) SFA in LD, KF, and TF depots. The RES fed lambs had greater ( < 0.05) -3 PUFA, eicosatrienoic acid (C20:3n3), eicosapentaenoic acid (C20:5n3, EPA), and trans-linolelaidic acid (C18:2n6t) in LD muscle. The conjugated linoleic acids (CLA) content was greater in the SF depots of the CON fed lambs compared to the RES fed lambs. Fatty acid ratios (unsaturated fatty acid; USFA:SFA, MUFA:SFA, PUFA:SFA), and percentage USFA in RES fed lambs were lesser in muscle and adipose tissue compared to CON fed lambs ( < 0.05), except SF depots. In RES fed lambs, EFA were less ( < 0.05) in LD and KF depots and the ratios of functional fatty acids were lesser in LD and some adipose tissues ( < 0.05), including lesser n-6:n-3 in KF and SF ( < 0.05) depots, lesser USFA, SFA, MUFA, SFA in LD, KF, and TF ( < 0.05) depots, and lesser PUFA and SFA in LD and TF ( < 0.05) depots. Results from this research demonstrate that sequential energy restriction, as might be experience during seasonal forage quality and quantity changes in natural grasslands, result in lesser intramuscular fat with associated lesser quality, as well as, changes in fatty acid composition in different fat depots, which has implications for both meat quality and animal physiological functions.

Effect of dietary restriction and subsequent re-alimentation on the transcriptional profile of hepatic tissue in cattle.

BackgroundCompensatory growth (CG) is an accelerated growth phenomenon observed in animals upon re-alimentation following a period of dietary restriction. It is typically utilised in livestock systems to reduce feed costs during periods of reduced feed availability. The biochemical mechanisms controlling this phenomenon, however, are yet to be elucidated. This study aimed to uncover the molecular mechanisms regulating the hepatic expression of CG in cattle, utilising RNAseq. RNAseq was performed on hepatic tissue of bulls following 125 days of dietary restriction (RES) and again following 55 days of subsequent re-alimentation during which the animals exhibited significant CG. The data were compared with those of control animals offered the same diet on an ad libitum basis throughout (ADLIB). Elucidation of the molecular control of CG may yield critical information on genes and pathways which could be targeted as putative molecular biomarkers for the selection of animals with improved CG potential.ResultsFollowing a period of differential feeding, body-weight and liver weight were 161 and 4 kg higher, respectively, for ADLIB compared with RES animals. At this time RNAseq analysis of liver tissue revealed 1352 significantly differentially expressed genes (DEG) between the two treatments. DEGs indicated down-regulation of processes including nutrient transport, cell division and proliferation in RES. In addition, protein synthesis genes were up-regulated in RES following a period of restricted feeding. The subsequent 55 days of ad libitum feeding for both groups resulted in the body-weight difference reduced to 84 kg, with no difference in liver weight between treatment groups. At the end of 55 days of unrestricted feeding, 49 genes were differentially expressed between animals undergoing CG and their continuously fed counterparts. In particular, hepatic expression of cell proliferation and growth genes were greater in animals undergoing CG.ConclusionsGreater expression of cell cycle and cell proliferation genes during CG was associated with a 100 % recovery of liver weight during re-alimentation. Additionally, an apparent up-regulation in capacity for cellular protein synthesis during restricted feeding may contribute to and sustain CG during re-alimentation. DEGs identified are potential candidate genes for the identification of biomarkers for CG, which may be incorporated into future breeding programmes.Electronic supplementary materialThe online version of this article (doi:10.1186/s12864-016-2578-5) contains supplementary material, which is available to authorized users.

Growth attenuation is associated with histone deacetylase 10-induced autophagy in the liver

Our previous data suggested that the histone deacetylase (HDAC) SIRT1 is involved in mediating the effect of nutrition on growth. The aim of the present research was to study the mechanism by which additional HDACs may be involved in nutrition-induced linear growth. The in vivo studies were performed in young male Sprague–Dawley rats that were either fed ad libitum (AL) or subjected to 10days of 40% food restriction (RES) and then refed (CU). For in vitro studies, Huh7 hepatoma cells were used. Food restriction led to significant reduction in liver weight, concomitant with increased autophagy (i.e., a decrease in the level of P62 and an increase in the expression level of Ambra1 and Atg16L2 genes in the RES group). At the same time, we found that the level of HDAC10 was significantly increased. Overexpression of HDAC10 in Huh7 hepatoma cells led to reduced cell viability and increased autophagy as shown by increased conversion of LC3-I to LC3-II. An increase in the level of HDAC10 was also obtained when mTOR was inhibited by Rapamycin. siRNA directed against HDAC10 abolished the effect of Rapamycin on cell viability and Ambra1 and Atg16L2 increased expression. These results suggest that increased levels of HDAC10 may mediate the effect of malnutrition on growth attenuation and autophagy. Deciphering the role of epigenetic regulation in the nutrition–growth connection may pave the way for the development of new forms of treatment for children with growth disorders.

Body composition and plasma lipid and stress hormone levels during 3 weeks of feed restriction and refeeding in low birth weight female pigs.

Compensatory growth in response to feed restriction (FR) affects deposition rates of lean and adipose tissues. It is, however, unclear whether pigs with low birth weight differ from their counterparts with normal birth weight with regard to compensatory growth. Female littermate pigs with low (UW; 1.1 kg) and normal (NW; 1.5 kg) birth weight were fed to appetite (control, CON) or feed restricted (RES) at 60% of DMI of the CON group between 78 and 98 d of age and subsequently refed at the level of the CON group until 131 d of age. Subgroups of pigs were slaughtered at 75, 98, 104, and 131 d of age to compare BW and body composition. Blood samples were taken at 98 and 119 d of age to analyze plasma metabolites and hormones. At birth UW pigs were shorter and had lower BW until 131 d of age than NW pigs ( < 0.05). Feed intake per kilogram of BW was greater in UW than in NW pigs ( < 0.01). The UW and NW pigs differed in carcass composition as indicated by greater relative subcutaneous fat at 75 d ( < 0.1), greater shoulder back fat ( < 0.05) at 98 d, and lower carcass weight at 131 d with greater abdominal and subcutaneous neck back fat in UW compared with NW pigs ( < 0.05). During FR, BW gain of RES pigs was lower than in NW pigs. The RES pigs showed greater feed intake after termination of FR until 131 d than CON pigs ( < 0.01). At 98 d RES pigs were leaner than CON pigs ( < 0.05). After 6 d of refeeding (104 d) relative fat depot weights were still smaller ( < 0.03) in RES pigs than in CON pigs. After 5 wk of refeeding, RES pigs had lower abdominal fat weights and greater plasma cortisol levels than CON pigs ( < 0.05). Regarding the plasma metabolite and hormone response, at 98-d fasting levels of plasma NEFA and glycerol were greater in RES than in CON pigs ( < 0.05), and after the drop in their levels after morning feeding ( < 0.001), plasma NEFA and glycerol and also triacylglycerol increased until the next meal in RES vs. CON pigs ( < 0.01). Plasma cortisol was greater in RES pigs after 3-wk FR ( < 0.05), whereas only a trend for increased plasma adrenalin concentrations in RES pigs at the end of the FR period and after 5 wk of refeeding was found ( < 0.1). In conclusion, UW pigs at 75 d of age (20 to 23 kg BW) had greater subcutaneous fat, whereas at 131 d (61 to 68 kg BW) they showed greater abdominal fat than NW pigs, suggesting that subcutaneous fat is deposited earlier than abdominal fat. The FR caused similar changes in body composition, plasma lipids, and stress hormones in UW and NW pigs.

Bone quality is affected by food restriction and by nutrition-induced catch-up growth.

Growth stunting constitutes the most common effect of malnutrition. When the primary cause of malnutrition is resolved, catch-up (CU) growth usually occurs. In this study, we have explored the effect of food restriction (RES) and refeeding on bone structure and mechanical properties. Sprague-Dawley male rats aged 24 days were subjected to 10 days of 40% RES, followed by refeeding for 1 (CU) or 26 days long-term CU (LTCU). The rats fed ad libitum served as controls. The growth plates were measured, osteoclasts were identified using tartrate-resistant acid phosphatase staining, and micro-computed tomography (CT) scanning and mechanical testing were used to study structure and mechanical properties. Micro-CT analysis showed that RES led to a significant reduction in trabecular BV/TV and trabecular number (Tb.N), concomitant with an increase in trabecular separation (Tb.Sp). Trabecular BV/TV and Tb.N were significantly greater in the CU group than in the RES in both short- and long-term experiments. Mechanical testing showed that RES led to weaker and less compliant bones; interestingly, bones of the CU group were also more fragile after 1 day of CU. Longer term of refeeding enabled correction of the bone parameters; however, LTCU did not achieve full recovery. These results suggest that RES in young rats attenuated growth and reduced trabecular bone parameters. While nutrition-induced CU growth led to an immediate increase in epiphyseal growth plate height and active bone modeling, it was also associated with a transient reduction in bone quality. This should be taken into consideration when treating children undergoing CU growth.

Integrative analyses of hepatic differentially expressed genes and blood biomarkers during the peripartal period between dairy cows overfed or restricted-fed energy prepartum.

Using published dairy cattle liver transcriptomics dataset along with novel blood biomarkers of liver function, metabolism, and inflammation we have attempted an integrative systems biology approach applying the classical functional enrichment analysis using DAVID, a newly-developed Dynamic Impact Approach (DIA), and an upstream gene network analysis using Ingenuity Pathway Analysis (IPA). Transcriptome data was generated from experiments evaluating the impact of prepartal plane of energy intake [overfed (OF) or restricted (RE)] on liver of dairy cows during the peripartal period. Blood biomarkers uncovered that RE vs. OF led to greater prepartal liver distress accompanied by a low-grade inflammation and larger proteolysis (i.e., higher haptoglobin, bilirubin, and creatinine). Post-partum the greater bilirubinaemia and lipid accumulation in OF vs. RE indicated a large degree of liver distress. The re-analysis of microarray data revealed that expression of >4,000 genes was affected by diet × time. The bioinformatics analysis indicated that RE vs. OF cows had a liver with a greater lipid and amino acid catabolic capacity both pre- and post-partum while OF vs. RE cows had a greater activation of pathways/functions related to triglyceride synthesis. Furthermore, RE vs. OF cows had a larger (or higher capacity to cope with) ER stress likely associated with greater protein synthesis/processing, and a higher activation of inflammatory-related functions. Liver in OF vs. RE cows had a larger cell proliferation and cell-to-cell communication likely as a response to the greater lipid accumulation. Analysis of upstream regulators indicated a pivotal role of several lipid-related transcription factors (e.g., PPARs, SREBPs, and NFE2L2) in priming the liver of RE cows to better face the early postpartal metabolic and inflammatory challenges. An all-encompassing dynamic model was proposed based on the findings.

Effect of maternal nutrient restriction and melatonin supplementation from mid to late gestation on vascular reactivity of maternal and fetal placental arteries

IntroductionMaternal nutrient restriction and decreased scotophase concentrations of melatonin have been associated with severely compromised pregnancies. We hypothesized that melatonin supplementation in a compromised pregnancy enhances the bradykinin (BK)-induced relaxations of placental arteries thereby ensuring sufficient umbilical blood flow to the developing fetus. MethodsPregnant ewes (n = 31) were fed an adequate (ADQ) or nutrient restricted (RES) diet supplemented with 5 mg of melatonin (MEL) or without melatonin (CON) from day 50 to 130 of gestation. On day 130 of gestation, the maternal (caruncular; CAR) and fetal (cotyledonary; COT) placental arteries were suspended in organ chambers for isometric tension recording. ResultsThere were no treatment or dietary effects on CAR arteries for any vasoactive agent. However, in COT arteries, MEL ewes were more sensitive (P < 0.01) to bradykinin-induced relaxation than CON ewes. There was a melatonin by nutritional level interaction (P < 0.01) with sodium nitroprusside-induced relaxation of COT arteries where CON-RES were more sensitive to sodium nitroprusside compared to CON-ADQ, which was in contrast to when ewes were fed MEL. There was a significant melatonin by nutritional interaction (P = 0.04) for responsiveness to norepinephrine. The sensitivity of the COT arteries to norepinephrine in CON-RES ewes was decreased compared to CON-ADQ. Melatonin supplementation, regardless of maternal dietary intake, resulted in COT arteries having similar responsiveness to CON-RES ewes. ConclusionAn increase in placental vessel sensitivity to bradykinin-induced relaxation may contribute to melatonin-induced increases in umbilical artery blood flow.

A Serum Component Mediates Food Restriction–Induced Growth Attenuation

Proper nutrition in terms of calories and essential food components is required to maximize longitudinal growth in children. Our previous study showed that prepubertal male rats subjected to 10 days of 40% food restriction (RES) exhibited a dramatic reduction in weight and epiphyseal growth plate height, as well as changes in gene expression and microRNAs (miRNAs) in the epiphyseal growth plate. These findings reversed rapidly after renewal of the regular food supply (catch-up [CU]). To further elucidate the mechanisms underlying the nutrition-growth association, serum collected from the RES and CU rats and control rats fed ad libitum (AL) was added to the culture medium of the chondrocyte cell line ATDC5 (instead of fetal calf serum). Serum from the RES group induced a reduction in cell viability (25%, P < .05) concomitant with an increase in cell differentiation compared with that for the AL group serum. The most interesting observation, in our opinion, was the significant reduction in the expression of specific miRNAs, including the chondro-specific miR-140. These effects were not observed for serum from refed (CU) rats. Serum levels of IGF-I, leptin, and fibroblast growth factor 21 were reduced by food restriction. The addition of IGF-I and leptin to the culture increased cell viability, whereas fibroblast growth factor 21 reduced it, suggesting the involvement of IGF-I, leptin, and possibly other still unidentified serum factors in chondrocyte cell growth. In conclusion, specific miRNAs respond to nutritional cues, and these effects are mediated by serum-borne factors. These results may promote the development of superior interventions for children with malnutrition and growth abnormalities.

Administration of a novel plant extract product via drinking water to post-weaning piglets: effects on performance and gut health

The present study evaluated the effects of a novel plant extract (PE) product (GrazixTM) on the performance and gut health of weaned piglets challenged with Escherichia coli. The PE was a standardised mixture of green tea leaves (Camellia sinensis) and pomegranate fruit (Punica granatum) obtained by using the LiveXtractTM process. A total of 144 piglets were weaned at 24 days and allocated to 8 for a 35-day experiment with a 2×2×2 factorial design comparing different treatments (water without product (CT) or 8 μl/kg per day PE in drinking water (PE)), feeding regimens (ad libitum (AD) or restricted (RE)) and oral E. coli challenges on day 9 (sham (−) or infected (+)). There were six pens per group with three piglets per pen. On day 35, 24 of the RE feeding piglets were slaughtered. It was found that PE supplementation increased the average daily gain (ADG) from day 28 to day 35 (P=0.03) and increased the gain to feed ratio (G : F) from day 7 to day 14 (P=0.02). RE feeding led to lower feed intake in piglets during the 1st week (P<0.01), 2nd week (P=0.06), 3rd week (P=0.05), and throughout the course of the overall study period (P=0.05). E. coli challenge decreased the ADG and G : F ratio from day 7 to day 14 (P=0.08 and <0.01, respectively) and increased the faecal score (higher values indicate more severe diarrhoea) on days 14, 21, 28 and 35 (P<0.01). PE supplementation decreased the faecal score in the challenged piglets during the 1st week post-challenge (P<0.01). E. coli challenge increased the faecal E. coli level on day 14 (P=0.03) and increased the Enterobacteriaceae level on day 35 (P<0.01). Reduced faecal E. coli was observed on days 14 and 35 (P=0.05 and 0.02, respectively), and reduced Enterobacteriaceae (P<0.01) was found on day 35 in the PE animals. RE feeding increased the faecal Lactobacillus, Enterobacteriaceae and E. coli levels on day 35 (P=0.02, <0.01 and <0.01, respectively). These results suggest that PE supplementation may improve the gut health status of post-weaning piglets and counteract some of the negative effects that occur when piglets are challenged with E. coli.

A NON-LINEAR ABSOLUTELY-STABLE EXPLICIT NUMERICAL INTEGRATION ALGORITHM FOR STIFF INITIAL-VALUE PROBLEMS

The time-step in integration process has two restri ctions. The first one is the time step restriction due to accuracy requirement τac and the second one is the time-step restriction du e to stability requirement τst . The most of explicit methods have small stability regio ns and consequently small τst . It obliges us to solve stiff problems with small step size τst << τac . The implicit methods work well with stiff problem s but these methods require more work per step than the explici t methods. In this study, a non-linear absolutly st able explicit one step numerical integration algorithm i s proposed for solving non linear stiff initial-val ue problems in ordinary differential equations. The al gorithm is based on deriving a non-linear relation between the dependent variable and its derivatives from the well known Taylor expansion. The accuracy of the method depends on some unknown parameter inserted in Taylor expansion and determined from the error analysis. The accuracy and stability properties of the method are investigated and shown to yield at least third order and A-stable. The results obtained in the numerical exp eriments show the efficiency of the present method in solving stiff initial value problems.

Effect of heat stress on body temperature, respiratory frequency and performance of pigs

The effect of ambient temperature (AT) on body temperature (BT), respiratory frequency (RF), and performance of pigs was evaluated. Eighteen pigs (32.6 kg body weight) were distributed in three treatments: 1) housed at 25 °C (Comfort) and fed ad libitum (AL); 2) as in 1, but feed restricted (REST); 3) housed under heat stress (34.3 °C, HS). The AT, heat index (HI), BT, RF and pig performance were measured. The amount of feed consumed (FI) by HS pigs fed ad lib was the same offered to the REST pigs. Average HI in the Comfort and HS rooms was 81 and 102. Treatment results for AL, REST, and HS were: BT, 38.3, 37.9, 39.2 °C; RF, 60, 49, 103; weight gain (ADG), 688, 525, 501 g/d; feed intake (FI), 1.47, 1.20, 1.17, respectively. HS pigs had higher BT, RF but lower ADG and FI (P&lt;0.01) than those in comfort. AL pigs had higher BT, RF, ADG and FI than REST pigs (P&lt;0.01). BT and RF of HS pigs, measured from 0800 to 2000 h, increased from 38.4 to 39.6 °C and from 62 to 113, as AT increased from 26 to 42 °C. These results show a marked effect of AT on BT, RF, ADG and FI of pigs, and suggest that pigs are capable of overcoming rapid and huge AT changes when they are exposed to HS. Financial support by UABC.

Short-term feed intake is regulated by macronutrient oxidation in lactating Holstein cows

In addition to plasma metabolites and hormones participating as humoral signals in the control of feed intake, oxidative metabolic processes in peripheral organs also generate signals to terminate feeding. Although the degree of oxidation over longer periods is relatively constant, recent work suggests that the periprandial pattern of fuel oxidation is involved in regulating feeding behavior in the bovine. However, the association between periprandial oxidative metabolism and feed intake of dairy cows has not yet been studied. Therefore, the aim of this study was to elucidate possible associations existing between single feed intake events and whole-body net fat and net carbohydrate oxidation as well as their relation to plasma metabolite concentrations. To this end, 4 late-lactating cows equipped with jugular catheters were kept in respiratory chambers with continuous and simultaneous recording of gas exchange and feed intake. Animals were fed ad libitum (AL) for 24h and then feed restricted (RE) to 50% of the previous AL intake for a further 24h. Blood samples were collected hourly to analyze β-hydroxybutyrate (BHBA), glucose, nonesterified fatty acids (NEFA), insulin, and acylated ghrelin concentrations. Cross-correlation analysis revealed an offset ranging between 30 and 42min between the maximum of a feed intake event and the lowest level of postprandial net fat oxidation (FOXnet) and the maximum level of postprandial net carbohydrate oxidation (COXnet), respectively. During the AL period, FOXnet did not increase above −0.2g/min, whereas COXnet did not decrease below 6g/min before the start of the next feed intake event. A strong inverse cross-correlation was obtained between COXnet and plasma glucose concentration. Direct cross-correlations were observed between COXnet and insulin, between heat production and BHBA, between insulin and glucose, and between BHBA and ghrelin. We found no cross-correlation between FOXnet and NEFA. During RE, FOXnet increased with an exponential slope, exceeded the threshold of −0.2g/min as indicated by increasing plasma NEFA concentrations, and approached a maximum rate of 0.1g/min, whereas COXnet decayed in an exponential manner, approaching a minimal COXnet rate of about 2.5g/min in all cows. Our novel findings suggest that, in late-lactating cows, postprandial increases in metabolic oxidative processes seem to signal suppression of feed intake, whereas preprandially an accelerated FOXnet rate and a decelerated COXnet rate initiate feed intake.

Melatonin supplementation alters uteroplacental hemodynamics and fetal development in an ovine model of intrauterine growth restriction

Using a mid- to late-gestation ovine model of intrauterine growth restriction (IUGR), we examined uteroplacental blood flow and fetal growth during melatonin supplementation as a 2 × 2 factorial design. At day 50 of gestation, 32 ewes were supplemented with 5 mg of melatonin (MEL) or no melatonin (CON) and were allocated to receive 100% [adequate; (ADQ)] or 60% [restricted (RES)] of nutrient requirements until day 130 of gestation. Umbilical artery blood flow was increased from day 60 to day 110 of gestation in MEL vs. CON dams, while umbilical artery blood flow was decreased from day 80 to day 110 of gestation in RES vs. ADQ dams. At day 130 of gestation, uteroplacental hemodynamics, measured under general anesthesia, and fetal growth were evaluated. Uterine artery blood flow was decreased in RES vs. ADQ dams, while melatonin supplementation did not affect uterine artery blood flow. Total placentome weight and placentome number were not different between treatment groups. Fetal weight was decreased by nutrient restriction. Abdominal girth and ponderal index were increased in fetuses from MEL-ADQ dams vs. all other groups. Fetal biparietal distance was decreased in CON-RES vs. CON-ADQ dams, while melatonin supplementation rescued fetal biparietal distance. Fetal kidney length and width were increased by maternal melatonin treatment. Fetal cardiomyocyte area was altered by both maternal melatonin treatment and nutritional plane. In summary, melatonin may negate the consequences of IUGR during specific abnormalities in umbilical blood flow as long as sufficient uterine blood perfusion is maintained during pregnancy.