Normal Protein Diet Research Articles

Effects of Dietary Protein Quantity on Bone Quantity following Weight Loss: A Systematic Review and Meta-analysis

Research supports the hypothesis that higher total protein intake during weight loss promotes retention of lean soft tissue, but the effect of dietary protein quantity on bone mass, a lean hard tissue, is inconsistent. The purpose of this systematic review and meta-analysis was to assess the effect of dietary protein quantity [higher protein (HP): ≥25% of energy from protein or ≥1.0g · kg body wt-1 · d-1; normal protein (NP): <25% of energy from protein or <1.0g · kg body wt-1 · d-1] on changes in bone mineral density (BMD) and content (BMC; total body, lumbar spine, total hip, femoral neck) following a prescribed energy restriction. We hypothesized that an HP diet would attenuate the loss of BMD/BMC following weight loss in comparison to an NP diet. Two researchers systematically and independently screened 2366 publications from PubMed, Cochrane, Scopus, CINAHL, and Web of Science Core Collection and extracted data from 34 qualified publications. Inclusion criteria included the following: 1) healthy subjects ≥19 y; 2) a prescribed energy restriction; 3) measurements of total protein intake, BMD, and BMC; and 4) an intervention duration of ≥3 mo. Data from 10 of the 34 publications with 2 groups of different total protein intakes were extracted and used to conduct a random-effects model meta-analysis. A majority of publications (59%) showed a decrease in bone quantity following active weight loss, regardless of total protein intake. Statistically, the loss of total BMD (P=0.016; weighted mean difference: +0.006g/cm2; 95% CI: 0, 0.011 g/cm2) and lumbar spine BMD (P=0.019; weighted mean difference: +0.017g/cm2; 95% CI: 0.001, 0.033 g/cm2) was attenuated with an HP versus an NP weight-loss diet. However, the clinical significance is questionable given the modest weighted mean difference and study duration. Higher total protein intake does not exacerbate but may attenuate the loss of bone quantity following weight loss.

Effects of Dietary Supplementation of Alpha-Ketoglutarate in a Low-Protein Diet on Fatty Acid Composition and Lipid Metabolism Related Gene Expression in Muscles of Growing Pigs.

Simple SummaryAlpha-ketoglutarate (AKG) is a critical intermediate in the tricarboxylic acid cycle. AKG has been reported to participate in energy production, promote protein synthesis, and improve amino acid metabolism. However, whether AKG functionally participates in the regulation of fat metabolism remains unknown. The objective of this experiment was to evaluate the impact of dietary supplementation with AKG on lipid metabolism in a pig model. The present results suggest that AKG supplementation in a reduced-protein diet could increase the intramuscular fat (IMF) and monounsaturated fatty acid (MUFA) contents in the biceps femoris muscles of pigs. These effects could be linked to the altered lipid metabolism related gene mRNA expression, which promotes the absorption and deposition of fatty acids in the muscle tissues. The results of this study can provide better understanding of the mechanisms by which dietary AKG modulates muscle lipid metabolism in pigs, and this could help to improve pig feeding strategies and supply high-quality pork for humans.The aim of the current study was to investigate whether dietary supplementation with alpha-ketoglutarate (AKG) in a reduced crude protein (CP) diet would affect fatty acid composition and lipid metabolism related gene expression in the muscles of growing pigs. A total of 27 Large White × Landrace growing pigs at 44 ± 1 d of age (11.96 ± 0.18 kg) were randomly allocated to three treatments (n = 9). Dietary treatments included: (1) normal protein diet with 20% crude protein (CP) (NP); (2) a low crude protein diet formulated to contain approximately 17% CP (LP); and (3) a low crude protein diet with 17% CP supplemented with 1% AKG at the expense of regular corn components (ALP). The experimental trial lasted 35 d. The results showed that compared with the NP and LP diets, supplementation with AKG in a low-protein diet increased the intramuscular fat (IMF), oleic acid (C18:1n-9), and monounsaturated fatty acid (MUFA) contents (p < 0.05), and tended to increase the percentage of palmitoleic acid (C16:1) and stearic acid (C18:0) (p < 0.10) in the biceps femoris and longissimus dorsi muscles of growing pigs. These effects may be associated with increased relative mRNA expression levels of fatty acid synthase (FAS), acetyl-CoA carboxylase (ACC), adipocyte determination and differentiation factor 1 (ADD1), fatty acid binding protein 4 (FABP4), and stearoyl-CoA desaturase (SCD) in skeletal muscle, indicating that AKG might be involved in the differential regulation of some key lipogenic genes in skeletal muscles of pigs.

Paternal diet impairs F1 and F2 offspring vascular function through sperm and seminal plasma specific mechanisms in mice.

A low protein diet had minimal effects on paternal cardiovascular function or renin-angiotensin system activity. Paternal low protein diet modified F1 neonatal and adult offspring renin-angiotensin system activity and cardiovascular function in a sperm and/or seminal plasma specific manner. Paternal low protein diet modified F1male offspring testicular expression of central epigenetic regulators. Significant changes in F2 neonatal offspring growth and tissue angiotensin-converting enzyme activity were programmed by paternal low protein diet in a sperm and/or seminal plasma specific manner. Although the impact of maternal diet on adult offspring health is well characterized, the role that a father's diet has on his offspring's health remains poorly defined. We establish the significance of a sup-optimal paternal low protein diet for offspring vascular homeostasis and define the sperm and seminal plasma specific programming effects on cardiovascular health. Male C57BL6mice were fed either a control normal protein diet (NPD; 18% protein) or an isocaloric low protein diet (LPD; 9% protein) for a minimum of 7weeks. Using artificial insemination, in combination with vasectomized male mating, we generated offspring derived from either NPD or LPD sperm (devoid of seminal plasma) but in the presence of NPD or LPD seminal plasma (devoid of sperm). We observed that either LPD sperm or seminal fluid at conception impaired adult offspring vascular function in response to both vasoconstrictors and dilators. Underlying these changes in vascular function were significant changes in serum, lung and kidney angiotensin-converting enzyme (ACE) activity, established in F1 offspring from 3weeks of age, maintained into adulthood and present also within juvenile F2 offspring. Furthermore, we observed differential expression of multiple central renin-angiotensin system regulators in adult offspring kidneys. Finally, paternal diet modified the expression profiles of central epigenetic regulators of DNA methylation, histone modifications and RNA methylation in adult F1male testes. These novel data reveal the impact of sub-optimal paternal nutrition on offspring cardiovascular well-being, programming offspring cardiovascular function through both sperm and seminal plasma specific mechanisms over successive generations.

Technique and outcome of domino liver transplantation from patients with maple syrup urine disease: Expanding the donor pool for live donor liver transplantation.

Domino liver transplantation (DLT) using liver allografts from patients with metabolic disorders enhances organ utilization. Short- and long-term course and outcome of these patients can impact the decision to offer this procedure to patients, especially those with diseases that can potentially be cured with liver transplant. We reviewed the outcomes of DLT from maple syrup urine disease (MSUD) patients in our large academic pediatric and adult transplant program. All patients receiving DLT were analyzed retrospectively with a minimum of one-year follow-up period for patient and donor characteristics, early and late postoperative complications and patient and graft survival with their MSUD donors in terms of age, weight, MELD/PELD scores, cold ischemia time, postoperative leucine levels, and peak ALT (alanine aminotransferase) levels during the first 48 postoperative hours. Between 2006 and May 2019, 21 patients underwent domino liver transplantation with live donor allografts from MSUD patients. Four patients transplanted for different metabolic diseases are focus of a separate report. Seventeen patients with minimum one-year follow-up period are reported herein. The indications were primary sclerosing cholangitis (PSC, n=4), congenital hepatic fibrosis (CHF, n=2), alpha-1 antitrypsin deficiency (A-1 ATD, n=2), progressive familial intrahepatic cholestasis (PFIC, n=2), cystic fibrosis (n=1), primary biliary cirrhosis (PBC, n=1), neonatal hepatitis (n=1), embryonal sarcoma (n=1), Caroli disease (n=1), hepatocellular carcinoma (HCC, n=1), and chronic rejection after liver transplantations for PSC (n=1). All patients and grafts survived at median follow-up of 6.4years (range 1.2-12.9years). Median domino recipient age was 16.2years (range 0.6-64.6years) and median MSUD recipient age was 17.6years (range 4.8-32.1years). There were no vascular complications during the early postoperative period, one patient had portal vein thrombosis 3years after DLT and a meso-Rex bypass was successfully performed. Small for size syndrome (SFSS) occurred in reduced left lobe DLT recipient and was managed successfully with conservative management. Biliary stricture developed in 2 patients and was resolved by stenting. Comparison between DLT and MSUD recipients' peak postoperative ALT results and PELD/MELD scores showed lower levels in DLT group (P-value <.05). Patient and graft survival in DLT from MSUD donors was excellent at short- and long-term follow-up. Metabolic functions have been normal in all recipients on a normal unrestricted protein diet. Ischemia preservation injury based on peak ALT was significantly decreased in DLT recipients. Domino transplantation from pediatric and adult recipients with selected metabolic diseases should be increasingly considered as an excellent option and alternative to deceased donor transplantation, thereby expanding the living donor pool. This, to date, is the largest world experience in DLT utilizing livers from patients with MSUD.

P: 20 EID-UL-AZHA (Muslim's Festival of Sacrifice): Increased Frequency of Spontaneous Encephalopathy, Whether This Is Secondary to Consumption of High Protein Diet?

BACKGROUND: Protein restricted diet once was the cornerstone of the management of Hepatic encephalopathy, latter no evidence showed significant benefits. However sub group of cirrhotics are intolerant to dietary proteins, especially animal proteins. We compared precipitants of encephalopathy and effect of animal proteins consumption during the festival of EID-UL-AZHA METHODS: A retrospective comparative cross sectional study was conducted and analyzed hospital data of AIMS (Asian institute of medical sciences, Hyderabad, Pak.). Patients of cirrhosis were enrolled with clinically diagnosed hepatic encephalopathy in two groups. Group A was categories with patients admitted 15 days before EID-Ul-AZHA and Group B includes patients admitted on EID UL AZHA day and up to 15 days afterward. Patients with neurological deficit and suspected CNS infection were excluded. Patient of both groups were assessed to compare precipitant factors for encephalopathy that includes infections, electrolytes imbalance, upper GI bleed, constipation, AKI and drugs. Dietary history regarding normal protein diet and high protein diet (animal proteins &gt; 1.5 g/kg/day) were also collected and compared in both groups. RESULTS: Out of 378 screened patients, 92 were presented with encephalopathy. All patients were Muslims with mean age 54.36 ± 11 yrs. Majority 66.3% were males and 33.7% were females. Precipitating factors were identified in 70.2% and 62.9% in group A and B respectively. Precipitating factor remain unidentified in 29.8% patients in group A and 37.1% in group B. 98.2% patients in group A were taking usual diet, only 1.8% consumed high (animal) protein diet, while in group B 51.4% patients were on usual diet and 48.6% consumed high (animal) protein diet. A comparable rise in frequency of spontaneous hepatic encephalopathy (without an identified precipitating factors) was observed in group B and 76.9% patients out of them were consuming high (animal) protein diet. CONCLUSIONS: A comparable rise in frequency spontaneous hepatic encephalopathy was observed during and/or post event of EID-UL-AZHA, majority had consumed high (animal) proteins. Consumption of meat (animal proteins) could be the possible contributing factor. Generally protein restriction is not recommended in cirrhotics but, still in sub group of cirrhotics who are protein intolerant, protein restriction or substitution of source of protein is inevitable. A further multicenter study is necessary at a larger scale to find out characteristic of patients who are intolerant to animal proteins.

Amelioration of neurobehavioral and cognitive abilities of F1 progeny following dietary supplementation with Spirulina to protein malnourished mothers

Early life adversities (stress, infection and mal/undernutrition) can affect neurocognitive, hippocampal and immunological functioning of the brain throughout life. Substantial evidence suggests that maternal protein malnutrition contributes to the progression of neurocognitive abnormalities and psychopathologies in adolescence and adulthood in offspring. Maternal malnutrition is prevalent in low and middle resource populations. The present study was therefore undertaken to evaluate the effects of dietary Spirulina supplementation of protein malnourished mothers during pregnancy and lactation on their offspring’s reflex, neurobehavioral and cognitive development. Spirulina is a Cyanobacterium and a major source of protein and is being used extensively as a dynamic nutraceutical against aging and neurodegeneration. Sprague Dawley rats were switched to low protein (8% protein) or normal protein (20% protein) diet for 15 days before conception. Spirulina was orally administered (400 mg/kg/b.wt.) to subgroups of pregnant females from the day of conception throughout the lactational period. We examined several parameters including reproductive performance of dams, physical development, postnatal reflex ontogeny, locomotor behavior, neuromuscular strength, anxiety, anhedonic behavior, cognitive abilities and microglia populations in the F1 progeny. The study showed improved reproductive performance of Spirulina supplemented protein malnourished dams, accelerated acquisition of neurological reflexes, better physical appearance, enhanced neuromuscular strength, improved spatial learning and memory and partly normalized PMN induced hyperactivity, anxiolytic and anhedonic behavior in offspring. These beneficial effects of Spirulina consumption were also accompanied by reduced microglial activation which might assist in restoring the behavioral and cognitive skills in protein malnourished F1 rats. Maternal Spirulina supplementation is therefore proposed as an economical nutraceutical/supplement to combat malnutrition associated behavioral and cognitive deficits.

Impact of gestational low protein diet and postnatal bisphenol A exposure on chemically induced mammary carcinogenesis in female offspring rats.

This study evaluated the effect of gestational low protein diet (LPD) and/or postnatal bisphenol A (BPA) exposure on mammary gland development and carcinogenesis in female offspring. Pregnant Sprague-Dawley rats were fed a normal protein diet (NPD, 17% protein) or LPD (6% protein). At weaning, female offspring were distributed in four groups (NPD, LPD, NPD + BPA, and LPD + BPA) and received vehicle or BPA in drinking water (0.1%), during postnatal day (PND) 21 to 51. On PND 51, some female offspring were euthanized or received a single dose of 7,12-dimethylbenzoanthracene (DMBA, 30 mg/kg, i.g.) and were euthanized on PND 250. On PND 51, neither gestational LPD nor postnatal BPA exposure, individually or in combination, significantly altered the development of mammary gland tree, mean number of terminal structures or estrogen receptor beta (ER-β), proliferating cell nuclear antigen (PCNA) or caspase-3 protein expression in the mammary tissue. A significant reduction in mammary epithelial area (%) was observed in both LPD groups and a significant increase in ER-α protein expression was detected only in LPD group. In LPD + BPA group was observed a significant increase in both fat pad area (%) and in mean number of mammary epithelial cells positive for progesterone receptor (PR). On PND 250, the groups that received BPA presented lower latency and higher tumor incidence and tumor multiplicity and LPD + BPA group more aggressive tumors. These findings suggest that postnatal BPA exposure associated with gestational LPD is able to induce morphological changes in the mammary gland and increase susceptibility to mammary carcinogenesis.

Protein malnutrition impairs bone marrow endothelial cells affecting hematopoiesis

Protein malnutrition (PM) affects hematopoiesis leading to bone marrow (BM) hypoplasia and arrests hematopoietic stem cells (HSC) in G0/G1 cell cycle phases, which cause anemia and leukopenia. Hematopoiesis is mainly regulated by BM niches where endothelial cells (EC) present a key regulatory role. Thus, our objective is to evaluate whether PM affects the modulatory capacity of EC on hematopoiesis. C57BL/6 male mice received for 5 weeks a normal protein diet (12% casein) or a low protein diet (2% casein). MSC were isolated and differentiated invitro into EC and the synthesis of SCF, Ang-1, CXCL-12, IL-11, TGF-β and G-CSF were evaluated. The HSC and hematopoietic progenitors were quantified and the EC capacity to modulate the hematopoietic system was also evaluated. Moreover, the ability of PM bone marrow to support hematopoieisis was assessed by proliferation of infused leukemic myelo-monoblasts cells. PM decreases HSC and hematopoietic progenitor pool and promotes cell cycle arrest and a lower proliferation rate of leukemic myelo-monoblasts. PM also committed hematopoietic regulatory characteristics from EC, resulting in the modification of both cell cycle pattern and hematopoietic differentiation. BM microenvironment is compromised in PM, and since PM disturbs EC, it becomes one of the factors responsible for the hematopoietic cell cycle arrest and impairment of HSC differentiation.

Supplementation exogenous bile acid improved growth and intestinal immune function associated with NF-κB and TOR signalling pathways in on-growing grass carp (Ctenopharyngodon idella): Enhancement the effect of protein-sparing by dietary lipid

This study investigated the effects of bile acid (BA) supplementation on growth performance, intestinal immune function and the mRNA expression of the related signalling molecules in on-growing grass carp (Ctenopharyngodon idella). A total of 540 healthy grass carp (mean weight 179.85 ± 1.34 g) were fed a normal protein and lipid (NPNL) diet containing 29% crude protein (CP) and 5% ether extract (EE), and five low-protein and high-lipid (LPHL) diets (26% CP, 6% EE) with graded levels of BA (0–320 mg/kg diet) for 50 days. The fish were then challenged with Aeromonas hydrophila for 14 days. The results indicated that compared with the NPNL diet, the LPHL diet (unsupplemented BA) suppressed the growth performance, intestinal development and enteritis resistance capability and impaired the partial intestinal immune function of on-growing grass carp. Whereas in the LPHL diet, optimal BA supplementation significantly improved fish growth performance (percent weight gain, specific growth rate, feed intake and feed efficiency) and intestinal growth and function (intestine weight, intestine length and intestosomatic index), increased beneficial bacteria Lactobacillus and Bifidobacterium amounts, decreased harmful bacteria Aeromonas and Escherichia coli amounts, elevated lysozyme and acid phosphatase activities, increased complement (C3 and C4) and immunoglobulin M contents, and upregulated β-defensin-1, hepcidin, liver expressed antimicrobial peptide 2A (LEAP-2A), LEAP-2B, Mucin2, interleukin 10 (IL-10), IL-11, transforming growth factor (TGF)-β1, TGF-β2, IL-4/13A (not IL-4/13B), TOR, S6K1 and inhibitor of κBα (IκBα) mRNA levels. In addition, optimal BA supplementation in the LPHL diet downregulated tumour necrosis factor α (TNF-α), interferon γ2 (IFN-γ2), IL-1β, IL-6, IL-8, IL-15, IL-17D, IL-12p35, IL-12p40 (rather than proximal intestine (PI) or mid intestine (MI), nuclear factor kappa B p65 (NF-κB p65) (except NF-κB p52), c-Rel, IκB kinase β (IKKβ), IKKγ (except IKKα), eIF4E-binding proteins (4E-BP)1 and 4E-BP2 mRNA levels in all three intestinal segments of on-growing grass carp (P < 0.05). These findings suggest that BA supplementation in the LPHL diet improves growth and intestinal immune function of fish. Furthermore, 240 mg/kg BA supplementation in the LPHL diet was superior to the NPNL diet in improving growth and enhancing intestinal immune function of fish. Finally, based on percent weight gain, feed intake, protecting fish against enteritis, lysozyme activity in MI and acid phosphatase activity in distal intestine (DI), the optimal BA supplementation for on-growing grass carp were estimated to be 168.98, 170.23, 166.67, 176.50 and 191.97 mg/kg diet, respectively.

Effects of low-protein diet on the intestinal morphology, digestive enzyme activity, blood urea nitrogen, and gut microbiota and metabolites in weaned pigs

ABSTRACTThis study investigated the effects of low-protein diet supplemented with Lysine (Lys), Methionine (Met), Threonine (Thr), and Tryptophan (Trp) on small intestine morphology, enzyme activity, blood urea nitrogen, and gut microbiota and metabolites in weaned piglets. Eighteen weaned pigs weighing an average of 9.57 kg received one of three treatments: a normal protein diet with 20% crude protein (CP, diet [NP]), a moderately reduced protein diet with 17% CP (MP), or a low-protein diet with 14% CP (LP). All three diets were supplemented with Lys, Met, Thr and Trp to meet essential amino acid requirements for post-weaned piglets according to the NRC (2012). Following a 45 d study period, piglets on the LP and MP diets demonstrated atrophic small intestinal morphology, with decreased villus heights and lower ratios of villus height to crypt depth (p < 0.05); pepsin activity in the stomach was also reduced in these two groups (p < 0.05). Increased plasma cholesterol and decreased blood urea nitrogen presented in the MP and LP groups compared with the NP group (p < 0.05). Overall, gastrointestinal hormones were not affected by dietary protein levels with the exception of reduced somatostatin levels in the MP and LP groups. Jejunum and colon microbiota were not affected at either the phyla or genera level in any of the diets. Colonic ammonia nitrogen concentration was reduced in MP and LP groups. Dietary protein level had no effect on short chain fatty acids or biogenic amines. Our data suggest that reducing dietary protein levels by 3% (MP) or 6% (LP) in weaned pigs has the potential to decrease nitrogen emissions and impaired digestive capacity. Therefore, dietary protein level cannot be reduced by more than 3% in consideration of maladaptive changes to small intestinal morphology and pepsin activity in weaned piglets.

Effects of Wheel Running on Health-Related Outcomes in Growth Restricted Mice.

Growth restriction caused by early life undernutrition leads to an increased risk of cardiovascular disease, hypertension, type II diabetes and sarcopenia. However, limited information exists on the beneficial effects of physical activity engagement in growth restricted individuals. PURPOSE: To determine the effects of wheel running access on health-related outcomes in growth restricted mice. METHODS: Mice were undernourished in gestation (GUN, N=15) or lactation (PUN, N=17) by feeding FVB mothers a low protein diet (8% protein). The control group (CON, N=14) was fed a normal protein diet (20% protein) throughout gestation and lactation. At postnatal day 21 (PN21), all pups were weaned and refed with the control diet. At PN45, mice were singly housed and either given access to a free moving running wheel (VOL-wheel access) or used as a non-active control (SED-sedentary). At PN70 a maximal treadmill test was performed to determine exercise capacity, and at PN72 echocardiography was performed to evaluate cardiovascular function. RESULTS: Final body weight showed SED PUN (M: 21.22±2.07 g, F: 17.42±1.7 g) weighed significantly (P=0.0002) less than SED CON (M: 26.83±2.2 g, F: 20.65±1.65 g) and SED GUN (M: 26.9±1.5 g, F: 19.98±1.6 g) mice, while the VOL CON mice (M: 24.9±1.62 g, F: 23.0±1.42 g) were significantly larger (P=0.0441) than VOL PUN mice (M: 22.6±2.7 g, F: 20.0±2.26 g). Wheel access improved treadmill running time to exhaustion in CON (P=0.045, VOL: 1078±47s, SED: 936±40s), and GUN mice (P=0.042; VOL 1021±39s SED 890±44s), but not PUN mice (P=0.59; VOL 933±31s and SED 908±32s). Echoes showed heart rate was significantly lowered (P=0.002) in GUN mice (VOL:366±11 bpm; SED: 421±10 bpm) with running wheel access. Stroke volume was also significantly higher (P=0.02) in GUN mice (VOL: 27±1.2 uL; SED: 23±1.1 uL). VOL CON (1.64±0.08mm) mice had a significantly greater (P=0.05) left ventricular anterior wall thickness at systole than SED CON (1.38±0.08mm). CONCLUSION: Voluntary wheel access does not attenuate growth-restriction in PUN mice nor does it improve maximal treadmill tests. This is due to a lack of improvements in cardiac function for PUN mice, despite access to voluntary wheel running, while GUN mice did improve.

Dietary Branched-Chain Amino Acids Regulate Food Intake Partly through Intestinal and Hypothalamic Amino Acid Receptors in Piglets

Strategies to increase feed intake are of great importance for producing more meat in swine production. Intestinal and hypothalamic amino acid receptors are found to largely participate in feed intake regulation. The purpose of the current research is to study the function of branched-chain amino acid (BCAA) supplementation in the regulation of feed intake through sensors that can detect amino acids in piglets. Twenty-four piglets were assigned one of four treatments and fed one of the experimental diets for either a short period (Expt. 1) or a long period (Expt. 2): a normal protein diet (NP, 20.04% CP), a reduced-protein diet (RP, 17.05% CP), or a reduced-protein test diet supplemented with one of two doses of BCAAs (BCAA1, supplemented with 0.13% l-isoleucine, 0.09% l-leucine, and 0.23% l-valine; BCAA2, supplemented with the 150% standardized ileal digestibility BCAA requirement, as recommended by the National Research Council (2012)). In Expt. 1, no differences were observed in the feed intake among piglets fed different diets ( P > 0.05). In Expt. 2, compared with the RP group, the feed intake of piglets was significantly increased after sufficient BCAAs were supplemented in the BCAA1 group, which was associated with decreased cholecystokinin secretion ( P < 0.05), down-regulated expression of type-1 taste receptors 1/3 (T1R1/T1R3) in the intestine, as well as increased expression of pro-opiomelanocortin, activated general control nonderepressible 2 (GCN2), and eukaryotic initiation factor 2α (eIF2α) in the hypothalamus ( P < 0.05). However, the feed intake was decreased for unknown reasons when the piglets were fed a BCAA over-supplemented diet. Our study confirmed that a BCAA-deficient diet inhibited feed intake through two potential ways: regulating the amino acid T1R1/T1R3 receptor in the intestine or activating GCN2/eIF2α pathways in the hypothalamus.

MiRNAs, target genes expression and morphological analysis on the heart in gestational protein-restricted offspring.

Gestational protein restriction was associated with low birth weight, hypertension and higher prevalence of cardiac disorders in adults. Several mechanisms, including epigenetics, could be related with the cardiovascular phenotype on protein-restricted offspring. Thus, we investigated the morphological cardiac effects of gestational protein restriction and left ventricle miRNAs and target genes expression pattern in both 12-day and 16-week old gestational protein-restricted male offspring. Pregnant Wistar rats were allocated into two groups, according to protein supply during pregnancy: NP (normal protein diet- 17%) or LP (low protein diet—6%). Dams on the gestational protein-restricted diet had lower body weight gain and higher food intake. Gestational protein-restricted offspring had low birth weight, followed by rapidly body weight recovery, hypertension, and increased myocytes cross-sectional area and collagen fraction at 16-week old age. At 12-days old, miR-184, miR-192, miR-376c, miR-380-3p, miR-380-5p, miR-451, and miR-582-3p had increased expression, and miR-547 and miR-743a had decreased expression in the gestational protein-restricted left ventricle. At 16-week old, let-7b, miR-125a-3p, miR-142-3p, miR-182 and miR-188-5p had increased expression and let-7g, miR-107, miR-127, miR-181a, miR-181c, miR-184, miR-324-5p, miR-383, miR-423-5p and miR-484 had decreased expression in gestational protein-restricted left ventricle. Target predicted gene expression analysis showed higher expression of Dnmt3a, Oxct1, Rictor and Trps1 and lower expression of Bbs1 and Calml3 in 12-day old protein-restricted offspring. 16-week old protein-restricted offspring had higher expression of Adrbk1, Bbs1, Dnmt3a, Gpr22, Inppl1, and Oxct1 genes. In conclusion, gestational protein restriction was related to offspring low birth weight, increased systolic blood pressure and morphological heart alterations that could be related to early heart miRNA expression changes that perpetuate into adulthood and which are associated with the regulation of essential genes involved in cardiovascular development, heart morphology, function, and metabolism.

Renal hypertrophic signaling triggers activation of kidney immune response and accelerates cystogenesis in polycystic kidney disease

BackgroundAutosomal dominant polycystic kidney disease (ADPKD) is the most common genetic kidney disease with the predominant form resulting from mutations in the gene, PKD1. The disease severity is highly variable even among families with the same PKD1 gene mutation and factors other than genetics may affect cystogenesis. Protein load or unilateral nephrectomy (UNx: 1K) results in glomerular hyperfiltration and renal hypertrophy which both accelerates kidney cyst growth in PKD mice. Children with PKD that exhibit glomerular hyperfiltration were shown to have a higher rate of cyst growth and faster decline in kidney function. Thus, hypertrophic signaling in PKD may clinically be a risk factor to accelerate cystogenesis.MethodsTo test the effect of renal hypertrophy in PKD, we used adult tamoxifen inducible Pkd1flox/flox mice with or without CAGG‐cre. Three weeks after cre induction, first group of mice underwent sham surgery or UNx to accelerate cyst formation and observed for 3 or 6 weeks. The second group of mice were fed with either high protein (60%), normal protein (18%) or low protein diet (6%) for a total of 6 weeks. Mice from both UNx and modified protein diet group were sacrificed at the end of the experiment and kidneys were harvested for RNA‐seq, histology, inflammatory cytokines and flow cytometry for kidney immune cell sorting.ResultsAnalysis of RNA sequencing data revealed that 1K compared to intact two kidney (2K) Pkd1 deficient mice show differentially expressed genes involved in activating/recruiting macrophages and production of pro‐inflammatory cytokines during the hypertrophic signaling. 1K compared to 2K Pkd1 mice had increased number of resident macrophage (CD11blo, F4/80 hi) but not infiltrating macrophages (CD11bhi, F4/80lo), increased inflammatory cytokine production, and severe cystic kidneys. Pkd1 deficient mice that were given a high protein diet compared to a low protein diet, resulted in activation of kidney immune cells, recruitment of inflammatory cytokines and worsening kidney cysts.ConclusionsRenal hypertrophic signaling triggered by either UNx or protein load in adult Pkd1 mice activates kidney immune cells, inflammatory cytokine production and accelerates cyst growth.Support or Funding InformationNIH K08DK106465, P30 DK074038, T32AI007051This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.

Influence of Low Protein Diet-Induced Fetal Growth Restriction on the Neuroplacental Corticosterone Axis in the Rat.

Objectives: Placental steroid metabolism is linked to the fetal hypothalamus-pituitary-adrenal axis. Intrauterine growth restriction (IUGR) might alter this cross-talk and lead to maternal stress, in turn contributing to the pathogenesis of anxiety-related disorders of the offspring, which might be mediated by fetal overexposure to, or a reduced local enzymatic protection against maternal glucocorticoids. So far, direct evidence of altered levels of circulating/local glucocorticoids is scarce. Liquid chromatography tandem-mass spectrometry (LC-MS/MS) allows quantitative endocrine assessment of blood and tissue. Using a rat model of maternal protein restriction (low protein [LP] vs. normal protein [NP]) to induce IUGR, we analyzed fetal and maternal steroid levels via LC-MS/MS along with the local expression of 11beta-hydroxysteroid-dehydrogenase (Hsd11b).Methods: Pregnant Wistar dams were fed a low protein (8%, LP; IUGR) or an isocaloric normal protein diet (17%, NP; controls). At E18.5, the expression of Hsd11b1 and 2 was determined by RT-PCR in fetal placenta and brain. Steroid profiling of maternal and fetal whole blood, fetal brain, and placenta was performed via LC-MS/MS.Results: In animals with LP-induced reduced body (p < 0.001) and placental weights (p < 0.05) we did not observe any difference in the expressional Hsd11b1/2-ratio in brain or placenta. Moreover, LP diet did not alter corticosterone (Cort) or 11-dehydrocorticosterone (DH-Cort) levels in dams, while fetal whole blood levels of Cort were significantly lower in the LP group (p < 0.001) and concomitantly in LP brain (p = 0.003) and LP placenta (p = 0.002). Maternal and fetal progesterone levels (whole blood and tissue) were not influenced by LP diet.Conclusion: Various rat models of intrauterine stress show profound alterations in placental Hsd11b2 gatekeeper function and fetal overexposure to corticosterone. In contrast, LP diet in our model induced IUGR without altering maternal steroid levels or placental enzymatic glucocorticoid barrier function. In fact, IUGR offspring showed significantly reduced levels of circulating and local corticosterone. Thus, our LP model might not represent a genuine model of intrauterine stress. Hypothetically, the observed changes might reflect a fetal attempt to maintain anabolic conditions in the light of protein restriction to sustain regular brain development. This may contribute to fetal origins of later neurodevelopmental sequelae.

INFLUENCE OF DIETARY POLYZYME ON THE PERFORMANCE OF BROILERS FED LOW CRUDE PROTEIN

The present experiment was carried out in order to investigate the effect of polyzyme (multi enzymes) in broiler diets with low protein levels on growth performance, carcass traits, some blood components and economic efficiency. A total of 180 Ross 308 unsexed one - day old broiler chicks, were distributed at random into 3 groups each in 3 replicates, 20 chicks each. Treatments were: T1: positive control, without Polyzyme, T2: negative control, without Polyzyme and T3: negative control, with o.5 g Polyzyme/ kg diet through the starter (1- 21 d) and finisher (22- 35 d) period. Results revealed that, chicks fed the negative control with polyzyme addition had significantly (P ≤ 0.05) higher body weight, body weight gain and performance index, while daily feed intake decreased. Feed conversion ratio, European efficiency index and economic efficiency improved also with the supplementation. Dressing, liver and heart % were increased in the same treatment (T3), while gizzard % was not affected. Polyzyme supplementation to low protein diet decreased serum total cholesterol and increased aspartic transaminase (AST) enzyme compared to the positive control (T1), meanwhile total protein, creatinine, glucose and alanine transaminase (ALT) enzyme were not affected, indicating the safety use of polyzyme at the level of 0.5 g/ kg diet. Data indicated that the beneficial economical effect of using polyzyme with low protein diet is to reach almost the same performance with normal protein diet.

Core body temperature, energy expenditure, and epinephrine during fasting, eucaloric feeding, and overfeeding in healthy adult men: evidence for a ceiling effect for human thermogenic response to diet

BackgroundIn homeothermic animals, approximately 50% of daily energy expenditure (EE) is spent to maintain a consistent core body temperature (CBT). In humans, little is known about CBT responses to feeding and overfeeding and their relationship to diet-related changes in EE. ObjectiveTo study the effects of feeding and overfeeding on CBT and its association with diet-induced thermogenesis (DIT). DesignFifty-three healthy men with normal glucose regulation and a wide range of body composition (mean ± SD, body fat: 25 ± 8%, range: 7–43%) had 24-h EE assessed during fasting in a whole-room indirect calorimeter with concomitant CBT measurement by ingestible capsules and 24-h urinary collection for catecholamine measurements. Changes in 24-h EE (DIT) and CBT compared to fasting were assessed during three normal-protein (20%) diets using a cross-over design: one eucaloric diet (EBL, 50% carbohydrate, n = 37) and two overfeeding diets with 200% energy requirements: a high-fat (FNP, 60% fat, n = 25) and a high-carbohydrate (CNP; 75% carbohydrate, n = 24) diet. ResultsThe average 24-h CBT (avgCBT) during fasting was 36.81 ± 0.14 °C (inter-individual CV = 0.4%) and positively correlated with 24-h urinary epinephrine (r = 0.61, p < 0.001), but not with body composition measures (p > 0.05). AvgCBT increased during EBL (Δ = 0.06 ± 0.11 °C, p = 0.002), FNP (Δ = 0.13 ± 0.14 °C, p < 0.001), and CNP (Δ = 0.19 ± 0.13 °C, p < 0.001) and associated with increased DIT during EBL (r = 0.43, p = 0.01, β = 31 kcal/day/0.1 °C) and FNP (r = 0.60, p = 0.002, β = 43 kcal/day/0.1 °C), but not CNP (p = 0.47). A ceiling effect for the increase in CBT, but not in DIT, was observed during feeding and, particularly, overfeeding. ConclusionsCBT increases with feeding and is moderately associated with DIT to a different degree depending on the macronutrient composition of the overfeeding diet. There is a ceiling effect such that individuals with a higher CBT during fasting have limited capacity to increase CBT with feeding. Because of body thermoregulatory mechanisms that maintain a constant CBT, these results indicate that CBT has a limited role in the inter-individual variability in DIT.

Can pentoxifylline recover reproductive parameters' damage induced by high-protein diet in male rats?

Introduction: Pentoxifylline (PEN) is a xanthine derivative used as a drug to inhibit the inflammatory factors activity, reduce blood viscosity and improve peripheral blood flow. Proteins play the most important role in reproductive parameters. The aim of the present investigation is to evaluate the effects of PEN against high-protein diet (HPD)-induced damage to the reproductive parameter of male rats. Materials and Methods: In this experimental study, 48 male rats were randomly divided to 8 groups: sham (normal protein diet) and HPD (35% protein) groups; PEN groups (25, 50 and 100 mg/kg) and HPD + PEN groups (25, 50 and 100 mg/kg). Animals of the HPD group have fed with high protein daily for 10 months. Daily PEN treatment was injected intraperitoneally. The sperm parameters, spermatogenesis index, total antioxidant capacity, testosterone level and seminiferous tubule diameter were analysed. Results: The values of all reproductive parameters reduced significantly in the HPD group compared to the sham group (P

Supplementation of Natural Antioxidants to Reduced Crude Protein Diets for Japanese Quails Exposed to Heat Stress

ABSTRACT The study aimed at comparing the effects of the supplementation of natural antioxidant sources to a reduced crude protein diet on the performance, carcass traits, blood parameters, liver antioxidant enzyme activities and meat lipid peroxidation of Japanese quails exposed to heat stress. A total of 640 14-day-old male Japanese quails were exposed to two different temperature treatments (TT): thermoneutral (TN) or heat stress (HS)and were fed five different dietary treatments (DTs). A normal-protein diet (SCP) was formulated according to the National Research Council (24% CP). The reduced crude protein diet (RCP) was formulated to contain 3% less protein than that of the SCP diet. Three additional diets were prepared by supplementing the RCP with200 mg/kg of α-tocopherol acetate (RCP+TA200), pomegranate peel extract (RCP+PPE200) or apple peel extract (RCP+APE200). HS significantly deteriorated the growth performance of quails throughout the experiment. Quails fed the SCP and RCP+PPE200 presented higher hematocrit values. Feeding the RCP+TA200 and RCP+PPE200 diets reduced the blood heterophil/lymphocyte (H/L) ratio compared with the other diets. Quails fed the SCP, RCP+TA200, RCP+PPE200 and RCP+APE200 diets presented higher liver catalase and glutathione peroxidase activities, plasma uric acid level, and lower meat malondialdehyde value at 7days of age compared with those fed the RCP diet. In conclusion, the results show that the extracts of pomegranate peel and apple peel can be used as alternative natural antioxidant sources to vitamin E in the diets of Japanese quails exposed to heat stress and fed a reduced crude protein diet.

The Divergent Effect of Maternal Protein Restriction during Pregnancy and Postweaning High-Fat Diet Feeding on Blood Pressure and Adiposity in Adult Mouse Offspring.

Obesity is a growing health crisis of pandemic proportions. Numerous animal and human studies have confirmed that obesity and related metabolic abnormalities, such as insulin resistance and cardiovascular disease, may be programmed during development by adverse maternal nutrition. We previously documented that offspring of female mice who were protein-restricted during pregnancy alone had no alterations to their body weights, but did display a considerable reduction in food intake, a finding which was linked to reduced expression levels of appetite regulatory genes in the hypothalamus. Whether such observations were accompanied by changes in metabolic and phenotypic parameters remained to be determined. Female pregnant MF-1 mice were fed, exclusively during the pregnancy period, a normal protein diet containing 18% casein (C) or an isocaloric protein-restricted diet containing 9% casein (PR). From birth, the lactating dams were fed a normal protein diet. At weaning, offspring were fed either the standard chow which contain 7% kcal fat (C) or high-fat diet (HF, 45% kcal fat). This yielded 4 experimental groups denoted by maternal diet/offspring diet: C/C, C/HF, PR/C, PR/HF. Our results showed that offspring adiposity was significantly increased in HF-fed offspring, and was not affected by the 50% reduction in protein content of the maternal diet fed during pregnancy. Similarly, blood glucose levels were higher in HF-fed offspring, regardless of protein content of the maternal diet. Systolic blood pressure, on the other hand, was significantly increased in both male and female offspring of dams fed the PR diet, and this was exacerbated by a postweaning HF diet. Our results show that maternal protein restriction leads to elevations in systolic blood pressure, which is exacerbated by a postweaning HF-diet. Our present findings suggest that, while changes in offspring adiposity brought about by exposure to maternal protein restriction during pregnancy may be restored by adequate maternal protein content during lactation, the same may not be true for systolic blood pressure, which was similarly impaired, regardless of the timing of maternal low-protein exposure.