scholarly journals Validation of a Feed Protocol in a Mouse Model That Mimics Marasmic Malnutrition

2021 ◽  
Vol 8 ◽  
Author(s):  
Taiana Ferreira-Paes ◽  
Paula Seixas-Costa ◽  
Elmo Eduardo Almeida-Amaral

Host nutritional status directly interferes with immunity and/or susceptibility to infectious diseases. To understand the mechanisms behind this relationship, the use of animal models and feeding protocols is necessary. In the literature, studies reporting marasmic malnutrition in mice are not common. In this context, the objective of this study was to validate a feed methodology that mimics marasmic malnutrition, examining the nutritional, biochemical, and hematological status in BALB/c mice. Weaned BALB/c mice were or were not fed a Restricted diet (36.26% carbohydrate, 8.79% protein, 4.95% fat, and 7.62 kJ/100 g). Some malnourished mice underwent a refed process with a Control diet (65.93% carbohydrate, 24.18% protein, 9.89% fat, and 15.24 kJ/100 g). The nutritional status of the mice was evaluated through phenotypic markers and hematological and biochemical parameters. Our results showed that the Restricted diet was able to induce mild malnutrition in mice, resulting in mouse weight loss of 12%, which could be reversed after refeeding. Malnourished mice demonstrated slow body growth and low body mass index (BMI) values. Malnourished mice also showed physical and behavioral changes, a reduction of 47.5% in leukocyte counts and a 2-fold increase in cholesterol levels. In conclusion, our feeding protocol was able to generate mild malnutrition and cause changes in the nutritional status of mice that could be similar to those observed in marasmic malnutrition.

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 95
Author(s):  
Imran Ramzan ◽  
Moira Taylor ◽  
Beth Phillips ◽  
Daniel Wilkinson ◽  
Kenneth Smith ◽  
...  

Elevated circulating branched-chain amino acids (BCAAs; isoleucine, leucine, and valine) are associated with obesity and type 2 diabetes (T2D). Reducing circulatory BCAAs by dietary restriction was suggested to mitigate these risks in rodent models, but this is a challenging paradigm to deliver in humans. We aimed to design and assess the feasibility of a diet aimed at reducing circulating BCAA concentrations in humans, while maintaining energy balance and overall energy/protein intake. Twelve healthy individuals were assigned to either a 7-day BCAA-restricted diet or a 7-day control diet. Diets were iso-nitrogenous and iso-caloric, with only BCAA levels differing between the two. The BCAA-restricted diet significantly reduced circulating BCAA concentrations by ~50% i.e., baseline 437 ± 60 to 217 ± 40 µmol/L (p < 0.005). Individually, both valine (245 ± 33 to 105 ± 23 µmol/L; p < 0.0001), and leucine (130 ± 20 to 75 ± 13 µmol/L; p < 0.05), decreased significantly in response to the BCAA-restricted diet. The BCAA-restricted diet marginally lowered Homeostatic Model Assessment of Insulin Resistance (HOMA-IR) levels: baseline 1.5 ± 0.2 to 1.0 ± 0.1; (p = 0.096). We successfully lowered circulating BCAAs by 50% while maintaining iso-nitrogenous, iso-caloric dietary intakes, and while meeting the recommended daily allowances (RDA) for protein requirements. The present pilot study represents a novel dietary means by which to reduce BCAA, and as such, provides a blueprint for a potential dietary therapeutic in obesity/diabetes.


2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
William Jonsson ◽  
Nicholas Margolies ◽  
Emily Mirek ◽  
Thomas Gettys ◽  
Tracy Anthony

Abstract Objectives Dietary restriction of the sulfur amino acids (SAAs) improves metabolic health in part via hepatic production of fibroblast growth factor 21 (FGF21). Transcriptional control of Fgf21includes regulation by ATF4 during low protein feeding. Therefore, we aimed to determine the impact of Atf4 deletion on FGF21 levels and associated metabolic outcomes in mice fed a SAA restricted diet. Methods Male and female mice lacking Atf4 globally or in hepatocytes only were fed either a SAA restricted diet (0.17% Met, 0% Cys) or a control diet (0.86% Met, 0% Cys) alongside littermate controls for up to 10 wk. Body mass and composition, energy expenditure and intake were measured. Blood and tissues were collected at specific time points. Transcript (RT-qPCR) and protein (ELISA and Western blot) abundances were analyzed by two factor ANOVA or Kruskal-Wallis Test, with alpha = 0.05. Results Independent of genotype, SAA restriction attenuated weight gain and reduced adiposity despite increased food intake. Improvements in body weight and composition strongly associated with increased energy expenditure regardless of genotype. Deletion of Atf4 did not prevent hepatic Fgf21 nor circulating FGF21 from increasing during chronic SAA restriction (P < 0.05, effect of diet). However, loss of hepatic Atf4 prevented increased circulating FGF21 at 12 h. Overall, males fed the SAA restricted diet induced hepatic Fgf21and serum FGF21 to a greater degree than females. Other known ATF4 targets in liver such as asparagine synthetase, Asns, showed significant induction in the livers of only intact SAA restricted mice. Conversely, loss of Atf4 exacerbated induction of the pro-apoptotic transcription factor Chop (P < 0.05) by SAA restriction. Conclusions Genetic loss of Atf4 delays but does not impede FGF21 production during dietary SAA restriction. Biological sex is a contributing factor to some of the physiological responses to dietary SAA restriction. Funding Sources DK109714 (TGA) and DK096311 (TWG).


Animals ◽  
2019 ◽  
Vol 9 (10) ◽  
pp. 781
Author(s):  
Osama Anwer Saeed ◽  
Awis Qurni Sazili ◽  
Henny Akit ◽  
Abdul Razak Alimon ◽  
Anjas Asmara Samsudin

Twenty-seven Dorper lambs were used to determine the effect of supplementing corn as a source of energy into the palm kernel cake (PKC) urea-treated rice straw basal diet on the blood metabolic profile and metals in lambs. The lambs were randomly allotted to three experimental treatments according to their initial body weight for a 120 day trial. Dietary treatments were: T1 (control diet) = 75.3% of PKC + 0% corn, T2 = 70.3% of PKC + 5% corn, and T3 = 65.3% of PKC + 10% corn. The results of this study indicated that copper (Cu), selenium (Se), zinc (Zn), and iron (Fe) concentration intake, retention, and its absorption from the gut and apparent mineral digestibility were highly significant for the levels of corn supplementation. The biochemical and hematological parameters remained within normal levels with the treatments, but the white blood cell, eosinophil count, cholesterol, and low-density lipoprotein cholesterol (LDL) were significantly higher in T3. Treatment 3 significantly increased the concentration of Se and Fe, while Zn was reduced in the blood serum of lambs on day 120. The result shows that the inclusion of corn has no effect on the hematological and biochemical parameters of lambs after incorporating corn into the PKC-based diet at 5% and 10%.


2002 ◽  
Vol 87 (6) ◽  
pp. 543-553 ◽  
Author(s):  
Robert E. Olson ◽  
Jean Chao ◽  
Donna Graham ◽  
Margaret W. Bates ◽  
Jessica H. Lewis

The aims of this study were to determine the total body phylloquinone and its metabolic turnover in human subjects using a tracer dose of [5-H3]phylloquinone containing 55·5×104MBq/mmol. Seven subjects aged 22 to 49 years were given 0·3 μg isotopic phylloquinone intravenously on a control diet (75 μg phylloquinone/d) and blood, urine and faeces were sampled periodically for 6 d. Five of these subjects were studied a second time after 3–8 weeks on a low-vitamin K diet (8 μg/d). The changes in the radioactivity of plasma phylloquinone with time were analysed by the method of residuals and fitted to a curve composed of two exponential components. The size of the exchangeable body pool was calculated by isotope dilution. Plasma phylloquinone levels fell during vitamin K restriction but the vitamin K-dependent coagulation factors did not change. After injection the first exponential decay curvet1/2was 1·0 (SD 0·47) H IN THE SUBJECTS ON THE CONTROL DIET AND 0·49 (sd 0·27) h after vitamin K restriction. On the control diet, the second exponentialt1/2was 27·6 (sd 124) h that did not change on the low-vitamin K diet (t1/2=25·1 (sd 13·5) h). These results indicate that the turnover time for phylloquinone in human subjects is about 1·5 d. Urinary excretion of3H-metabolites ranged from 30 % of the administered dose on the control diet to 38 % on the restricted diet and had the same turnover rate as the second component of the plasma decay curves. The exchangeable body pool of phylloquinone declined from about 1·0 μg/kg before restriction to lower values after vitamin K restriction. The faecal excretion of phylloquinone and its metabolites fell from 32 % of the administered dose on the control diet to 13 % on the restricted diet.


2020 ◽  
Vol 2020 ◽  
pp. 1-8
Author(s):  
Jessica Ayensu ◽  
Christopher Larbie ◽  
Reginald Adjetey Annan ◽  
Herman Lutterodt ◽  
Anthony Edusei ◽  
...  

Edible insects have emerged as an inexpensive alternative source of protein for reducing the burden of malnutrition worldwide. However, there is a dearth of evidence on its efficacy, and thus, the aim of this study was to investigate the effect of edible insect consumption on the nutritional status of female Wistar albino rats. The study assessed the subchronic effect of palm weevil larvae (PWL) and orange-fleshed sweet potato- (OFSP-) enriched biscuits (fortified biscuits (FB), plain biscuits (PB), biscuits fortified with PWL (PWB), and biscuits fortified with OFSP only (SPB)) as a model to predict the potential of PWL to improve the nutritional status of pregnant women in Ghana. Twenty-five female Wistar albino rats were randomly assigned to five experimental groups to receive one of the five feed supplements for 28 days. After which, the effects of treatment on haematological and biochemical parameters including lipid profile were assessed. No significant differences were observed with haematological (Hb) parameters. However, total cholesterol levels of the FB, PB, PWB, and SPB were significantly higher than in the N group. Apart from elevated total cholesterol concentrations, biscuits fortified with PWL had no adverse effects and can be a nutritious snack for maintaining acceptable HB levels.


2020 ◽  
Vol 9 ◽  
Author(s):  
A. S. Valable ◽  
M. P. Létourneau-Montminy ◽  
S. Klein ◽  
L. Lardic ◽  
F. Lecompte ◽  
...  

Abstract Chickens adapt to P and Ca restriction during the very first days of life by improving P utilisation efficiency. The present study was built to identify the mechanisms underlying this adaptive capacity, and to identify the optimal window of application of the restriction (depletion). A total of 1600 Cobb 500TM male broilers were used. During each phase (from age 0 to 4 d, 5 to 8 d, 9 to 18 d and 19 to 33 d), the animals received either a control diet (H) or a restricted diet (L) with reduced levels of non-phytate P (nPP) and Ca (between −14 and −25 % for both) with four dietary sequences: HHHH, HLHL, LHHL and LLHL. None of the feeding strategies affected growth. Tibia ash content at day 4 and 8 was impaired when the L diet was fed from 0 to 4 and 5 to 8 d, respectively (P = 0⋅038 and P = 0⋅005). Whatever the early restriction period or length between 0 and 8 d of age, the mineralisation delay was compensated by day 18. This was accompanied by an increased mRNA expression of the Ca transporter, CALB1, and an increased apparent ileal digestibility of Ca at day 8 (P < 0⋅001). This adaptation was limited to the starter phase in restricted birds. No effect was seen on P transporters mRNA or protein expression. In conclusion, birds adapted to mineral restriction by increasing Ca and nPP utilisation efficiencies. Depletion−repletion strategies are promising in improving the sustainability of broiler production but need to be validated in phytase-supplemented diets.


2002 ◽  
Vol 283 (3) ◽  
pp. R623-R630 ◽  
Author(s):  
Eric Bertin ◽  
Marie-Noëlle Gangnerau ◽  
Georges Bellon ◽  
Danièle Bailbé ◽  
Annick Arbelot De Vacqueur ◽  
...  

Fetal malnutrition is now proposed as a risk factor of later obesity and type II diabetes. We previously analyzed the long-term impact of reduced protein and/or energy intake strictly limited to the last week of pregnancy in Wistar rats. Three protocols of gestational malnutrition were used: 1) low-protein isocaloric diet (5 instead of 15%) with pair feeding to the mothers receiving the control diet, 2) restricted diet (50% of control diet), and 3) low protein-restricted diet (50% of low-protein diet). Only isolated protein restriction induced a long-term β-cell mass decrease. In the present study, we used the same protocols of food restriction to analyze their short-term impact (on day 21.5 of pregnancy) on β-cell mass development. A 50% β-cell mass decrease was present in the three restricted groups, but low-protein diet, either associated or not to energy restriction, increased fetal β-cell insulin content. Among all the parameters analyzed to further explain our results, we found that the fetal plasma level of taurine was lowered by low-protein diet and was the main predictor of the fetal plasma insulin level ( r = 0.63, P < 0.01). In conclusion, rat fetuses exposed to protein and/or energy restriction during the third part of pregnancy have a similar dramatic decrease in β-cell mass, and their ability to recover β-cell mass development retardation depends on the type of malnutrition used. Moreover, our results support the hypothesis that taurine might play an important role in fetal β-cell mass function.


Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 418-418
Author(s):  
Bruce S. Sachais ◽  
Tiffany Turrentine ◽  
Jeanine M. Dawicki-McKenna ◽  
Daniel J. Rader ◽  
M. Anna Kowalska

Abstract There is a presence of circulating, activated platelets in blood of patients with atherosclerosis, coronary disease and hypercholesterolemia. Upon activation, platelets release a large amount of platelet factor 4 (PF4), a platelet specific chemokine. Our laboratory has previously demonstrated several potentially proatherogenic properties of PF4 including alteration of LDL metabolism and cellular trafficking, and activation of NFkB, a proinflammatory transcription factor involved in atherosclerosis. We have also localized PF4 to human atherosclerotic lesions. However, to date, no direct in vivo evidence for the involvement of PF4 in atherogenesis. In the current study, we have bred PF4−/− mice onto two athero-susceptible backgrounds, WT-C57Bl/6(WT) and apoE−/−, to examine the importance of PF4 in atherogenesis. PF4−/− and PF4−/−apoE−/− (DKO) mice are viable and healthy, with no spontaneous bleeding disorders. In order to induce atherosclerosis, WT and PF4−/− mice were fed an atherogenic Paigen diet for 30 weeks (Study 1), while apoE−/− and DKO mice were fed a high fat Western style diet for 10 weeks (Study 2). Examination of lesions in the aortic roots of Study 1 animals demonstrated a 5-fold reduction in PF4−/− compared to WT mice (p = 0.008). Measurement of cholesterol levels demonstrated similar total and non-HDL cholesterol levels in WT and PF4−/− mice. However, HDL cholesterol was significantly increased in PF4−/− mice compared to WT (2.5-fold, p = 0.001). Examination of apoE−/− mice (Study 2) demonstrated similar changes, with DKO mice demonstrating a 2.7-fold reduction in aortic atherosclerosis (measured by the en face method; p = 0.03) and a 1.7-fold increase in HDL cholesterol (p = 0.02) compared to apoE−/− mice. Although platelet counts were increased by ~30% in mice lacking PF4, the activation state of the platelets in our mice at sacrifice (WT vs PF4−/− and apoE−/− vs DKO) were similar as measured by both p-selectin expression and annexin V binding. These data demonstrate, for the first time, that the platelet specific chemokine PF4 promotes atherosclerotic lesion development in vivo.


Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 867-867 ◽  
Author(s):  
Geoffrey L. Uy ◽  
Michael P. Rettig ◽  
Pablo Ramirez ◽  
Bruno Nervi ◽  
Camille N. Abboud ◽  
...  

The CXCR4-SDF-1 axis possesses a central role in the trafficking and retention of both normal and malignant stem cells in the bone marrow. Previous work from our laboratory established that in a murine model, a single dose of the CXCR4 antagonist, AMD3100, sensitizes AML blasts to chemotherapy supporting the premise that the interaction between AML blasts and the marrow microenvironment confers resistance to genotoxic stress (Nervi et al., ASH 2006). Here we examine the effects of repetitive dosing of AMD3100 on the kinetics of normal and leukemic mobilization. Following SQ injection of AMD3100 5mg/kg into B6/129 F1 mice daily for 5 days (n=8), we observed a 2.4 fold increase in total leukocyte counts with a 12.4 increase in CFU-GM when compared to 3 hours post injection (Fig 1A). No differences were seen in the degree of mobilization between d1 and d5 with WBC and CFU-GM counts returning to baseline after 24 hours. We next tested repetitive doses of AMD3100 in our mouse model of AML in which 106 blasts derived from leukemic mice carrying the PML-RARα fusion gene in the murine cathepsin G locus are adoptively transferred into genetically compatible secondary recipients. AMD3100 at 5mg/kg was then administered to these AML mice for 4 consecutive days. At 3 hrs post AMD3100 injection, we observed a 1.8 fold increase in peripheral leukocyte counts with a 4.5 fold increase in circulating blasts compared to baseline (n=3). Again, no significant differences are seen in the degree of mobilization from d1 to d4 (Fig 1B). Based on these preclinical data, we have initiated a phase I/II trial of AMD3100 plus mitoxantrone, etoposide and cytarabine (MEC) in relapsed or refractory AML in which AMD3100 is administered 4 hours prior to MEC daily for 5 consecutive days. To study the kinetics of human AML mobilization, we administered AMD3100 by SQ injection followed by 24hr observation period prior to chemotherapy. Two patients have been treated at the first dose level of AMD3100, 80 μg/kg. In pt #1 following AMD3100 mobilization, total WBC increased from 3 × 103/mm3 to a peak of 17 × 103/mm3 at 6 hours post-AMD3100 representing a 5.7 fold increase in total white count (Fig 2). In addition, the blasts (CD45dim, SSlow) increased by 7.3 fold. Similarly in pt #2, we observed a 2 fold increase in the total WBC from 2.5 to 5.1 × 103/mm3 with a 2.3 fold increase in blasts (CD45dim, SSlow). Mobilization of AML was confirmed in both patients through informative FISH for 11q23 (MLL). No adverse events have been observed during mobilization. These data provide the preclinical rationale for repetitive dosing of AMD3100 and direct clinical evidence that AMD3100 mobilizes human AML blasts into the peripheral circulation. Our trial of AMD3100 plus MEC in relapsed or refractory AML is ongoing. Figure 1. AMD3100 induced mobilization of (A) normal progenitors and (B) AML blasts Figure 1. AMD3100 induced mobilization of (A) normal progenitors and (B) AML blasts Figure 2. AMD3100 mobilization of human AML Figure 2. AMD3100 mobilization of human AML


2020 ◽  
Vol 10 (2) ◽  
pp. 173-180
Author(s):  
Teti Tejayanti

Abstrak   Latar belakang:  Status  gizi  perempuan  di  Indonesia  cenderung  memburuk.  Hasil  Riset  Kesehatan  Dasar (Riskesdas) menunjukkan bahwa kekurangan energi kronis (KEK) pada wanita usia reproduksi meningkat dari 13,6 persen pada 2007 menjadi 20,8 persen pada 2013. Ibu hamil yang kekurangan gizi akan berdampak buruk pada bayinya. Tujuan: Memperoleh determinan status gizi kurang yaitu KEK dan Indeks Massa Tubuh (IMT) rendah dari wanita hamil di Indonesia pada tahun 2013. Metode: Penelitian menggunakan data Riskesdas 2013. Analisis dilakukan dengan multivariat regresi logistik. Jumlah sampel adalah 7236 ibu hamil. Ibu hamil dikatakan KEK jika pertengahan lingkar lengan atas (LILA) < 23,5 cm dan IMT diukur dengan pendekatan metode Broca. Hasil: Determinan ibu hamil KEK dan IMT rendah adalah tinggal di perdesaan (AOR 1,20; 95% CI [1,11-1,13]), usia <20 tahun (AOR 1,62; 95% CI [1,60-1,65]), paritas 1 anak (AOR 2,04; 95% CI [2,02-2,06]), berpendidikan rendah (AOR 1,92; 95% CI [0,91-0,93]) dan status ekonomi rendah (AOR 3,36; 95% CI [3,31- 3,41]). Kesimpulan: Pendidikan harus ditingkatkan minimal hingga sekolah menengah atas sehingga pengetahuan gizi ibu meningkat dan kehamilan dini dapat dicegah. Ibu dengan status ekonomi rendah harus menjadi prioritas dalam pelayanan ibu dan upaya intervensi gizi.   Kata kunci: Sosial ekonomi, lingkar lengan atas, KEK, BMI, gizi ibu hamil.     Abstract   Background: The nutritional status of women in Indonesia tends to worsen. Basic Health Research (Riskesdas) showed that chronic energy deficiency (CED) among women of reproductive age increased from 13.6 percent in 2007 to 20.8 percent in 2013. Pregnant women who are lack of nutrition will have an impact on their babies. Objective: To determine the determinants of poor nutritional status which are CED and low body mass index (BMI) of pregnant women in Indonesia. Method: This study used 2013 Riskesdas data. The analysis was done using multivariate logistic regression. The total  sample  was 7236  pregnant  women.  Pregnant  women  with CED are those who  have mid-upper  arm circumference (MUAC) of less than 23.5 cm and BMI was measured by the Broca method approach. Results: The determinants of pregnant women with CED and low BMI are living in rural area (AOR 1.20; 95% CI [1.11-1.13]), age of <20 years (AOR 1.62; 95% CI [1.60-1.65]), having 1 child (AOR 2.04; 95% CI [2.02- 2.06]), having low education (AOR 1.92; 95% CI [0.91-0.93]) and low economic status (AOR 3.36; 95% CI [3.31- 3.41]). Conclusion: Education must be improved to at least high school degree, so that the mother's nutritional knowledge will increase, and early pregnancy will be prevented. Mothers with low economic status must be priority in maternal cervices and nutrition interventions.   Keywords: Socioeconomic, nutrition, mid-upper arm, CED, BMI, nutrition of pregnant women


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