Early-life nutrition influences thymic growth in male mice that may be related to the regulation of longevity

2009 ◽  
Vol 118 (6) ◽  
pp. 429-438 ◽  
Author(s):  
Jian-Hua Chen ◽  
Jane L. Tarry-Adkins ◽  
Chantal A.A. Heppolette ◽  
Donald B. Palmer ◽  
Susan E. Ozanne

Nutrition and growth rate during early life can influence later health and lifespan. We have demonstrated previously that low birthweight, resulting from maternal protein restriction during pregnancy followed by catch-up growth in rodents, was associated with shortened lifespan, whereas protein restriction and slow growth during lactation increased lifespan. The underlying mechanisms by which these differences arise are unknown. In the present study, we report that maternal protein restriction in mice influences thymic growth in early adult life. Offspring of dams fed a low-protein diet during lactation (PLP offspring) had significant thymic growth from 21 days to 12 weeks of age, whereas this was not observed in control mice or offspring of dams fed a low-protein diet during pregnancy (recuperated offspring). PCNA (proliferating-cell nuclear antigen) and SIRT1 (silent information regulator 1) protein levels at 21 days of age were significantly higher in the thymus from both PLP mice (P<0.001 and P<0.05 respectively) and recuperated mice (P<0.001 and P<0.01 respectively) compared with controls. At 12 weeks, PLP mice maintained a higher SIRT1 level, whereas PCNA was decreased in the thymus from recuperated offspring. This suggests that mitotic activity was initially enhanced in the thymus from both PLP and recuperated offspring, but remained sustained into adulthood only in PLP mice. The differential mitotic activity in the thymus from PLP and recuperated mice appeared to be influenced by changes in sex hormone concentrations and the expression of p53, p16, the androgen receptor, IL-7 (interleukin-7) and the IL-7 receptor. In conclusion, differential thymic growth may contribute to the regulation of longevity by maternal diet.

Cells ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 1094 ◽  
Author(s):  
Talita de Mello Santos ◽  
Marilia Martins Cavariani ◽  
Dhrielly Natália Pereira ◽  
Bruno César Schimming ◽  
Luiz Gustavo de Almeida Chuffa ◽  
...  

The maternal nutritional status is essential to the health and well-being of the fetus. Maternal protein restriction during the perinatal stage causes sperm alterations in the offspring that are associated with epididymal dysfunctions. Vascular endothelial growth factor (VEGF) and its receptor, VEGFr-2, as well as aquaporins (AQPs) are important regulators of angiogenesis and the epididymal microenvironment and are associated with male fertility. We investigated the effects of maternal protein restriction on epididymal angiogenesis and AQP expression in the early stages of postnatal epididymal development. Pregnant rats were divided into two experimental groups that received either a normoprotein (17% protein) or low-protein diet (6% protein) during gestation and lactation. At postnatal day (PND)7 and PND14, male offspring were euthanized, the epididymides were subjected to morphometric and microvascular density analyses and to VEGF-A, VEGF-r2, AQP1 and AQP9 expression analyses. The maternal low-protein diet decreased AQP9 and VEGFr-2 expression, decreased epididymal microvascularity and altered the morphometric features of the epididymal epithelium; no changes in AQP1 expression were observed at the beginning of postnatal epididymal development. Maternal protein restriction alters microvascularization and affects molecules involved in the epidydimal microenvironment, resulting in morphometric alterations related to a delay in the beginning of epididymis postnatal development.


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Mark R. Garbrecht ◽  
Fred S. Lamb

The placenta acts as a physiological barrier, preventing the transfer of maternal glucocorticoids to the developing fetus. This is accomplished via the oxidation, and subsequent inactivation, of endogenous glucocorticoids by the 11-β hydroxysteroid dehydrogenase type 2 enzyme (HSD2). Maternal protein restriction during pregnancy has been shown to result in a decrease in placental HSD2 expression and fetal glucocorticoid overexposure, especially late in gestation, resulting in low birth weight and “fetal programming” of the offspring. This dietary intervention impairs fetal growth and cardiovascular function in adult C57BL/6 offspring, but the impact on placental HSD2 has not been defined. The goal of the current study was to examine the effects of a maternal low-protein diet (18% versus 9% protein) on placental HSD2 gene expression and enzyme activity in mice during late gestation. In contrast to previous studies in rats, a maternal low-protein diet did not affect HSD2 protein or enzyme activity levels in the placentas of C57BL/6 mice and this was irrespective of the gender of the offspring. These data suggest that the effects of maternal protein restriction on adult phenotypes in C57BL/6 mice depend upon a mechanism that may be independent of placental HSD2 or possibly occurs earlier in gestation.


1995 ◽  
Vol 6 (5) ◽  
pp. 1379-1385
Author(s):  
J Coresh ◽  
M Walser ◽  
S Hill

Concerns have been raised about the possibility of protein restriction resulting in malnutrition and poor subsequent survival on dialysis. However, no studies have examined patients treated with protein restriction to determine their subsequent survival on dialysis. This study prospectively monitored 67 patients with established chronic renal failure (mean initial serum creatinine of 4.3 mg/dL) who were treated with a very low-protein diet (0.3 g/kg per day) supplemented with either essential amino acids or a ketoacid-amino acid mixture and observed closely for clinical complications. Forty-four patients required dialysis. Once dialysis was started, dietary treatment was no longer prescribed. The cumulative mortality rate during the first 2 yr after starting dialysis was 7% (95% confidence interval, 0 to 16%). During this period, only two deaths occurred compared with 11.5 deaths expected on the basis of national mortality rates adjusted for age, sex, race, and cause of renal disease (P = 0.002). However, the protective effect was limited to the first 2 yr on dialysis. Thereafter, mortality rates increased, resulting in a total of 10 deaths during 96.4 person-years of follow-up, which was not significantly lower than the 14.9 deaths expected (P = 0.25). Extrapolation of sequential serum creatinine measurements made before dietary treatment suggests that the improved survival cannot be due to the early initiation of dialysis. Although the lack of an internal control group and data on dialysis lends uncertainty, the large difference in mortality rate between these patients and the nationwide experience indicates that protein restriction and close clinical monitoring predialysis does not worsen and may substantially improve survival during the first 2 yr on dialysis. These findings point out the importance of studying predialysis treatments as a means for lowering mortality on dialysis.


2016 ◽  
Vol 8 (2) ◽  
pp. 178-187 ◽  
Author(s):  
E. Matsumoto ◽  
S. Kataoka ◽  
Y. Mukai ◽  
M. Sato ◽  
S. Sato

Maternal dietary restriction is often associated with cardiovascular disease in offspring. The aim of this study was to investigate the effect of green tea extract (GTE) intake during lactation on macrophage infiltration, and activation of adenosine monophosphate (AMP)-activated protein kinase (AMPK) and serine-threonine kinase Akt (Akt) in the hearts of weanlings exposed to maternal dietary protein restriction. Pregnant Wistar rats were fed control (C) or low-protein diets (LP) throughout gestation. Following delivery, the dams received a control or a GTE-containing control diet during lactation: control diet during gestation and lactation (CC), low-protein diet during gestation and lactation (LPC), low-protein diet during gestation and 0.12% GTE-containing low-protein diet during lactation (LPL), and low-protein diet during gestation and 0.24% GTE-containing low-protein diet during lactation (LPH). The female offspring were sacrificed at day 22. Biochemical parameters in the plasma, macrophage infiltration, degree of fibrosis and expression levels of AMPK and Akt were examined. The plasma insulin level increased in LPH compared with LPC. Percentage of the fibrotic areas and the number of macrophages in LPC were higher than those in CC. Conversely, the fibrotic areas and the macrophage number in LPH were smaller (21 and 56%, respectively) than those in LPC. The levels of phosphorylated AMPK in LPL and LPH, and Akt in LPH were greater than those in LPC. In conclusion, maternal protein restriction may induce macrophage infiltration and the decrease of insulin levels. However, GTE intake during lactation may suppress macrophage infiltration and restore insulin secretion function via upregulation of AMPK and insulin signaling in weanlings.


Endocrinology ◽  
2004 ◽  
Vol 145 (6) ◽  
pp. 3004-3013 ◽  
Author(s):  
E. A. Joanette ◽  
B. Reusens ◽  
E. Arany ◽  
S. Thyssen ◽  
R. C. Remacle ◽  
...  

2009 ◽  
Vol 103 (4) ◽  
pp. 608-616 ◽  
Author(s):  
Xiang Gao ◽  
Jianxiang Wu ◽  
Zheyi Dong ◽  
Can Hua ◽  
Huimin Hu ◽  
...  

Dietary protein restriction is one major therapy in chronic kidney disease (CKD), and ketoacids have been evaluated in CKD patients during restricted-protein diets. The objective of the present study was to compare the efficacy of a low-protein diet supplemented with ketoacids (LPD+KA) and a low-protein diet alone (LPD) in halting the development of renal lesions in CKD. 5/6 Nephrectomy Sprague–Dawley rats were randomly divided into three groups, and fed with either 22 % protein (normal-protein diet; NPD), 6 % protein (LPD) or 5 % protein plus 1 % ketoacids (LPD+KA) for 24 weeks. Sham-operated rats were used as controls. Each 5/6 nephrectomy group included fifteen rats and the control group included twelve rats. Proteinuria, decreased renal function, glomerular sclerosis and tubulointerstitial fibrosis were found in the remnant kidneys of the NPD group. Protein restriction ameliorated these changes, and the effect was more obvious in the LPD+KA group after 5/6 nephrectomy. Lower body weight and serum albumin levels were found in the LPD group, indicating protein malnutrition. Lipid and protein oxidative products were significantly increased in the LPD group compared with the LPD+KA group. These findings indicate that a LPD supplemented with ketoacids is more effective than a LPD alone in protecting the function of remnant kidneys from progressive injury, which may be mediated by ketoacids ameliorating protein malnutrition and oxidative stress injury in remnant kidney tissue.


2019 ◽  
Vol 8 (12) ◽  
pp. 573-581 ◽  
Author(s):  
Victoria P. de Quadros ◽  
Natalia Tobar ◽  
Lais R. Viana ◽  
Rogerio W. dos Santos ◽  
Paulo H. M. Kiyataka ◽  
...  

Objectives Insufficient protein ingestion may affect muscle and bone mass, increasing the risk of osteoporotic fractures in the elderly, and especially in postmenopausal women. We evaluated how a low-protein diet affects bone parameters under gonadal hormone deficiency and the improvement led by hormone replacement therapy (HRT) with 17β-oestradiol. Methods Female Wistar rats were divided into control (C), ovariectomized (OVX), and 17β-oestradiol-treated ovariectomized (OVX-HRT) groups, which were fed a control or an isocaloric low-protein diet (LP; 6.6% protein; seven animals per group). Morphometric, serum, and body composition parameters were assessed, as well as bone parameters, mechanical resistance, and mineralogy. Results The results showed that protein restriction negatively affected body chemical composition and bone metabolism by the sex hormone deficiency condition in the OVX group. The association between undernutrition and hormone deficiency led to bone and muscle mass loss and increased the fragility of the bone (as well as decreasing relative femoral weight, bone mineral density, femoral elasticity, peak stress, and stress at offset yield). Although protein restriction induced more severe adverse effects compared with the controls, the combination with HRT showed an improvement in minimizing these damaging effects, as it was seen that HRT had some efficacy in maintaining muscle and bone mass, preserving the bone resistance and minimizing some deleterious processes during the menopause. Conclusion Protein restriction has adverse effects on metabolism, leading to more severe menopausal symptoms, and HRT could minimize these effects. Therefore, special attention should be given to a balanced diet during menopause and HRT. Cite this article: Bone Joint Res 2019;8:573–581.


1990 ◽  
Vol 79 (6) ◽  
pp. 647-656 ◽  
Author(s):  
Gian Marco Ghiggeri ◽  
Fabrizio Ginevri ◽  
Giovanni Cercignani ◽  
Roberta Oleggini ◽  
Alessando Garberi ◽  
...  

1. A low protein diet prevents the development of proteinuria and glomerular damage in adriamycin experimental nephrosis without affecting renal haemodynamics. In this study the hypothesis was tested as to whether protein restriction is able to modulate the purine metabolic cycle and related enzymes such as xanthine oxidase, one of the putative effectors of adriamycin nephrotoxicity. 2. Renal activities of xanthine oxidase and purine nucleoside phosphorylase were markedly depressed in adriamycin-treated rats fed a 9% casein (low protein) diet compared with the group fed a 22% casein (normal protein) diet both 1 day after adriamycin administration and at the time of appearance of heavy proteinuria (day 15), whereas the activity of renal adenosine deaminase was unchanged. 3. The concentrations of the metabolic substrates of xanthine oxidase, i.e. hypoxanthine and xanthine, were constantly lower in renal homogenates of rats fed a low protein diet compared with those on a normal protein diet. In urine, uric acid, the product of hypoxanthine-xanthine transformation, was lower 1 day after adriamycin injection in protein-restricted rats compared with the group on a normal protein diet which showed a marked increase in its excretion. At the same time, the urinary efflux of adenosine 5′-monophosphate, which is the precursor nucleotide of the above-mentioned nucleosides and bases, was very high in rats fed a low protein diet, whereas it was absent in the group on a normal protein diet. 4. The progressive increment in proteinuria of glomerular origin (i.e. increased excretion of albumin and transferrin) typical of adriamycin-treated rats fed a normal protein diet was inhibited in the protein-restricted animals, which were normoproteinuric on day 10 and were only slightly proteinuric on day 15. 5. Like protein restriction, the pharmacological suppression of renal xanthine oxidase by dietary tungstate and the scavenging by dimethylthiourea of the putative free radical deriving from the action of xanthine oxidase, were associated with a similar (quantitative and qualitative) inhibition of glomerular proteinurea. 6. These data demonstrate that dietary protein restriction is associated with a block in purine metabolism within the kidney due to a marked reduction in the activities of two main enzymes of the cycle, i.e. purine nucleoside phosphorylase and xanthine oxidase, the latter being a putative effector of adriamycin nephrotoxicity. The partial reduction of proteinuria induced by a low protein diet is quantitatively and qualitatively comparable with the reduction induced by the specific block of renal xanthine oxidase or by the scavenging of OH · deriving from hypoxanthine and xanthine transformation. The crucial factor(s) determining protection against proteinuria in adriamycin nephrosis may be decreased xanthine oxidase activity in the kidney and inhibition of the O2 · and OH · production via the xanthine oxidase system.


2020 ◽  
Author(s):  
Leticia B Sene ◽  
Wellerson R Scarano ◽  
Adriana Zapparoli ◽  
Jose AR Gontijo ◽  
Patricia A Boer

Abstract Background: Authors demonstrated that gestational low-protein (LP) intake offspring presents a lower birthweight, reduced nephrons numbers and renal salt excretion, arterial hypertension and renal failure development when compared to normal protein (NP) intake rats in adulthood. The current study evaluated the miRNAs and predicted gene expression patterns in the 17-days LP (17-DG) fetal kidney to elucidate the molecular pathways and renal cell proliferation and differentiation profile. Methods: 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%). miRNA transcriptome sequencing (miRNA-Seq) was performed on the MiSeq platform and, RT-qPCR of predicted target genes, immunohistochemistry and morphological quantification from 17-DG offspring kidneys using previously described methods. Results: Forty-four expressed miRNAs, which 19 miRNA were up- and 25 downregulated, were identified in 17-DG LP fetuses compared to age-matched NP offspring. The study selected 7 miRNAs related to proliferation, differentiation, and cellular apoptosis processes. The study showed a reduced cell number, Six-2 and c-Myc immunoreactivity in metanephros cap (CM) and ureter bud (UB) in 17-DG LP fetuses. Also, Ki-67 immunoreactivity in CM was 48% lesser in LP compared to NP age-matched fetus. Conversely, in LP CM and UB β-catenin was 154% and 85% markedly enhanced, respectively and, mTOR immunoreactivity was also higher in LP CM (139%) and UB (104%) compared to the NP offspring. UB TGFβ-1 staining cells increased (about 30%) in the LP offspring. Otherwise, Zeb1 metanephros-stained, enhanced 30% in LP offspring without Zeb2 staining in both groups. Conclusions: The present study demonstrates that maternal protein restriction change miRNAs, mRNAs, and critical proteins expression involved in the processes of proliferation, differentiation, and apoptosis that occurs during renal development. The renal ontogenic dysfunction caused by maternal protein restriction promotes a reduced reciprocal interaction between CM and UB, and consequently, a programmed and expressive decrease in the nephron number fetuses.


Animals ◽  
2019 ◽  
Vol 9 (4) ◽  
pp. 180 ◽  
Author(s):  
Defu Yu ◽  
Weiyun Zhu ◽  
Suqin Hang

Using protein-restriction diets becomes a potential strategy to save the dietary protein resources. However, the mechanism of low-protein diets influencing pigs’ growth performance is still controversial. This study aimed to investigate the effect of protein-restriction diets on gastrointestinal physiology and gut microbiota in pigs. Eighteen weaned piglets were randomly allocated to three groups with different dietary protein levels. After a 16-week trial, the results showed that feeding a low-protein diet to pigs impaired the epithelial morphology of duodenum and jejunum (p < 0.05) and reduced the concentration of many plasma hormones (p < 0.05), such as ghrelin, somatostatin, glucose-dependent insulin-tropic polypeptide, leptin, and gastrin. The relative abundance of Streptococcus and Lactobacillus in colon and microbiota metabolites was also decreased by extreme protein-restriction diets (p < 0.05). These findings suggested that long-term ingestion of a protein-restricted diet could impair intestinal morphology, suppress gut hormone secretion, and change the microbial community and fermentation metabolites in pigs, while the moderately low-protein diet had a minimal effect on gut function and did not impair growth performance.


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