Low-protein Model Research Articles

Implementation and numerical aspects of the matlab solver designed for the solution of low protein model

In this paper, we discuss the implementation and numerical aspects of the Matlab solver designed for the solution of Low Protein Model (LPD). In this paper, we study the existence and uniqueness of the weak solution and we try to write some codes in Matlab which are based on Euler’s Method and several technics of programmation. subject to an initial condition 
 dM
 dt = µL − δM, (2)
 L(0) = 0 and M (0) = 0. (3)
 The code is based on Euler’s Method and several technics of programmation.

Suboptimal nutrition in utero causes DNA damage and accelerated aging of the female reproductive tract

Early life exposure to adverse environments can lead to a variety of metabolic and cardiovascular diseases in offspring. We hypothesize that female reproductive function may also be affected, with subsequent implications for fertility. We used an established maternal low-protein model where animals are born small but undergo rapid postnatal catch-up growth by suckling a control-fed dam (recuperated offspring). Markers of oxidative stress and cellular aging in reproductive tract tissues were assessed at 3 and 6 mo of age. Recuperated offspring had lower birth weight than controls (P<0.01) but caught up during lactation. 4-Hydroxynonenal (4HNE; an indicator of oxidative stress) was increased in recuperated animals compared with controls in both ovaries and oviducts at 6 mo. At 3 and 6 mo, ovaries and oviducts of recuperated offspring had increased mitochondrial (mt)DNA copy number (P<0.01). By contrast, germ-line cells showed no difference in mtDNA copy number, suggesting they were protected from suboptimal maternal nutrition. Oviduct and somatic ovarian telomere length declined more rapidly with age in recuperated animals. This accelerated cellular aging was associated with a declined ovarian reserve in developmentally programmed animals. These findings have significant clinical implications in light of worldwide trends to delayed childbearing.

Proteomic analysis of the maternal protein restriction rat model for schizophrenia: identification of translational changes in hormonal signaling pathways and glutamate neurotransmission.

Previous studies have found that some first onset schizophrenia patients show signs of impaired insulin signaling. Also, epidemiological studies have shown that periods of suboptimal nutrition including protein deficiencies during pregnancy can lead to increased incidence of metabolic conditions and psychiatric disorders in the offspring. For these reasons, we have carried out a molecular profiling analysis of blood serum and brain tissues from adult offspring produced by the maternal low protein (LP) rat model. The results showed similar changes to those seen in schizophrenia. Multiplex immunoassay profiling identified changes in the levels of insulin, adiponectin, and leptin along with alterations in inflammatory and vascular system-related proteins such as osteopontin, macrophage colony-stimulating factor 1, and vascular cell adhesion molecule 1. LC-MS(E) proteomic profiling showed that glutamatergic pathways were altered in frontal cortex, while signaling pathways and cytoskeletal proteins involved in hormonal secretion and synaptic remodeling were altered in the hypothalamus. Taken together, these studies indicate that the LP rat model recapitulates several pathophysiological attributes seen in schizophrenia patients. We propose that the LP model may have utility for drug discovery efforts, especially to identify compounds that modulate the metabolic and glutamatergic systems.

Poor maternal nutrition programmes a pro-atherosclerotic phenotype in ApoE-/- mice.

Numerous animal studies have consistently shown that early life exposure to LP (low-protein) diet programmes risk factors for CVD (cardiovascular disease) such as dyslipidaemia, high BP (blood pressure) and cardiac dysfunction in the offspring. However, studies on the effect of maternal under-nutrition on offspring development of atherosclerosis are scarce. Applying our LP model to the ApoE−/− atherosclerosis-prone mouse model, we investigated the development of atherosclerotic lesions in the aortic root of 6-month-old offspring. In addition, markers of plaque progression including SMA (smooth muscle actin) and Mac3 (macrophage marker 3) were studied. Pregnant dams were fed on a control (20% protein) or on an isocaloric LP diet (8% protein) throughout pregnancy and lactation. After weaning, male offspring were maintained on 20% normal laboratory chow. At 6 months of age, LP offspring showed a significantly greater plaque area (P<0.05) with increased cholesterol clefts and significantly higher indices of DNA damage compared with controls (P<0.05). The expression of HMG-CoA reductase (3-hydroxy-3-methyl-glutaryl-CoA reductase) (P<0.05) and LDL (low-density lipoprotein) receptor in the liver of LP offspring were increased. Furthermore, LP offspring had higher LDL-cholesterol levels (P<0.05) and a trend towards elevated insulin. There were no differences in other lipid measurements and fasting glucose between groups. These observations suggest that early exposure to an LP diet accelerates the development and increases the progression of atherosclerotic lesions in young adult offspring. Future studies are needed to elucidate the specific mechanisms linking in utero exposure to a diet low in protein to the development of atherosclerosis.

Elevated Insulin Sensitivity in Low‐protein Offspring Rats Is Prevented by a High‐fat Diet and Is Associated With Visceral Fat

This study tests the hypothesis that a high-fat postnatal diet increases fat mass and reduces improved insulin sensitivity (IS) found in the low-protein model of maternal undernutrition. Offspring from Wistar dams fed either a 20% (control (CON)) or 8% (low protein (LP)) protein diet during gestation and lactation were randomly assigned to a control (con) or cafeteria (caf) diet at weaning (21 days) until 3 months of age at which point IS was measured (hyperinsulinemic-euglycemic clamp). Fat mass, growth, energy intake (EI) and expenditure (EE), fuel utilization, insulin secretion, and leptin and adiponectin levels were measured to identify a possible role in any changes in IS. IS was increased in LP-con in comparison to CON-con animals. Cafeteria feeding prevented this increase in LP animals but had no effect in CON animals (insulin-stimulated glucose infusion rates (GIRs; mg/min/kg); CON-con: 13.9 +/- 1.0, CON caf: 12.1 +/- 2.1, LP-con: 25.4 +/- 2.0, LP-caf: 13.7 +/- 3.7, P < 0.05). CON-caf animals had similar percent epididymal white adipose tissue (%EWAT; CON-con: 1.71 +/- 0.09 vs. CON-caf: 1.66 +/- 0.08) and adiponectin (microg/ml: CON-con: 4.61 +/- 0.34 vs. CON-caf: 3.67 +/- 0.18) except hyperinsulinemia and relative hyperleptinemia in comparison to CON-con. Differently, LP-caf animals had increased %EWAT (LP-con: 1.11 +/- 0.06 vs. LP-caf: 1.44 +/- 0.08, P < 0.05) and adiponectin (microg/ml: LP-con: 5.38 +/- 0.39 vs. LP-caf: 3.75 +/- 0.35, P < 0.05) but did not show cafeteria-induced hyperinsulinemia or relative hyperleptinemia. An increased propensity to store visceral fat in LP animals may prevent the elevated IS in LP offspring.

Effector/memory T cells of the weanling mouse exhibit Type 2 cytokine polarization in vitro and in vivo in the advanced stages of acute energy deficit

Our objective was to determine whether the polarizing cytokine profile of the effector/memory T-cell compartment reflects the profound decline of cell-mediated inflammatory competence that characterizes acute prepubescent malnutrition. Weanling C57BL/6J mice were permitted free access to a complete purified diet, free access to an isocaloric low-protein diet or restricted intake of the complete diet for 14 days. First, interleukin (IL)-4 and interferon (IFN)-γ concentrations generated in vitro by splenic and nodal effector/memory T cells were assessed following exposure to plate-bound anti-CD3. Second, net systemic production of IFN-γ and IL-4 by the effector/memory T-cell compartment was assessed by the in vivo cytokine capture assay following anti-CD3 stimulation. In vitro stimulation generated less IFN-γ ( P=.002) but more IL-4 ( P=.05) by T cells from the restricted-intake group relative to the age-matched control group. Similarly, in vivo stimulation generated low serum levels of antibody-captured IFN-γ in the restricted-intake group vis-à-vis the age-matched control group ( P=.01), while the IL-4 response was sustained ( P=.39). By contrast, the 14-day low-protein model exhibited no change in T-cell cytokine signature either in vitro or in vivo. However, following extended consumption of the low-protein diet (26 days), carcass energy losses exceeded those of the 14-day protocol and serum levels of in vivo antibody-captured IFN-γ were low after anti-CD3 challenge relative to the age-matched control group ( P=.02), while levels of captured IL-4 remained unaffected ( P=.07). Acute weanling malnutrition elicits a Type 2 polarizing cytokine character on the part of the effector/memory T-cell compartment, but only in the most advanced stages of energy decrement.

Prenatal Dietary Docosahexaenoic Acid Supplementation in Combination with Protein Restriction Does Not Affect Blood Pressure in Adult Wistar Rats

Recent findings indicate that prenatal protein restriction, which leads to elevated blood pressure in adult rats, results in decreased levels of docosahexaenoic acid (DHA) in neonatal rat brain. In light of the evidence of a relationship between dietary DHA and adult blood pressure, the purpose of this study was to ascertain whether prenatal dietary supplementation with DHA would prevent the development of hypertension associated with maternal protein restriction. Throughout gestation, female Wistar rats were fed isocaloric diets containing either 18% casein+10% corn oil (CON; control), 9% casein+10% corn oil (LP; low-protein) or 9% casein+8.5% corn oil+1.5% DHASCO (LP+0.6% DHA). DHA increased levels of DHA in neonatal forebrain but there were no effects of LP. At 10 weeks there were no dietary effects on blood pressure measured on four consecutive days using tail-cuff plethysmography. There were also no significant effects measured at 30 weeks, using femoral artery catheterisation, despite adequate power to detect a 10 mm Hg difference. Trends in corticosterone measurements suggested higher stress reactivity in the LP group. These results do not provide strong support for the prenatal low protein model of hypertension and a relation with dietary DHA.

The maternal endocrine environment in the low-protein model of intra-uterine growth restriction.

Many adult diseases, including type 2 diabetes, hypertension and cardiovascular disease, are related to low birth weight. The mechanistic basis of this relationship is not known. To investigate the role of fetal undernutrition, we used a rat model of maternal protein restriction in which dams were fed a diet containing 80 g protein/kg (v. 200 g/kg in the control group) throughout gestation and lactation. Offspring were born smaller than controls and in adulthood developed diabetes, hyperinsulinaemia and tissue insulin resistance. To determine possible mechanisms of fetal programming, circulating levels of several hormones were measured in maternal plasma at gestational days 14, 17 and 21 and fetal plasma at gestational day 21. Several differences were noted at day 14, when glucose concentrations in maternal and feto-placental blood were raised significantly (P=0.04 and P=0.0001 respectively); insulin levels in the low-protein (LP) dams were raised (P=0.04), prolactin levels were raised (P=0.047) and progesterone levels were reduced (P=0.02). Circulating 17beta-oestradiol in the LP dams was raised by 35 % over those of the controls from day 17 to day 21 (P=0.008). A significant decrease in maternal leptin levels (P=0.004) was observed at gestation on day 21. Neither oestradiol nor leptin levels were altered in the fetal circulation at day 21. Maternal and fetal corticosterone levels were comparable with control levels, suggesting that they do not initiate the programming effects in this model. Our present results suggest that maternal protein restriction imposes changes in maternal levels of glucose, insulin, prolactin, progesterone, oestradiol and leptin; these changes could influence the programming of eventual adult disease in the developing fetus.

Dietary protein restriction in pregnancy induces hypertension and vascular defects in rat male offspring.

It is established that dietary protein restriction of pregnant rats results in their offspring developing hypertension. However, to date no studies have investigated peripheral vascular function of offspring using the low protein model. Therefore, the aim of the study was to assess isolated resistance artery function from adult male offspring of control (C, 18% casein) and protein-restricted (PR, 9% casein) pregnant dams at two different ages. The birthweight of PR offspring did not significantly differ from that of C offspring. Systolic blood pressure was significantly elevated in PR compared with C (p < 0.05). Maximal vascular contraction to phenylephrine and the thromboxane analog U46619 were similar in C and PR offspring at postnatal d 87 and 164. Relaxation induced by the endothelium-dependent vasodilators acetylcholine or bradykinin was significantly reduced in the PR group (p < 0.05). Relaxation to the endothelium-independent vasodilator sodium nitroprusside and phosphodiesterase type 3 inhibitor cilostamide was less in the PR offspring compared with C (p < 0.01). Dietary protein restriction in pregnancy induces hypertension and vascular dysfunction in male offspring. Abnormalities in the nitric oxide-cGMP pathway may explain the defect in endothelium-dependent and -independent relaxation. Reduced vasodilation may be a potential mechanism underlying the elevated systolic blood pressure observed in this model.

Mechanisms Underlying the Programming of Small Artery Dysfunction: Review of the Model Using Low Protein Diet in Pregnancy in the Rat

Human and animal studies have shown that unbalanced maternal nutrition is associated with the development of cardiovascular and metabolic disease in adulthood. In the Southampton maternal low protein model (SMLP), protein deprivation (50%) throughout pregnancy in rats leads to elevated blood pressure in adult offspring. Impaired peripheral arterial function may contribute to the cardiovascular dysfunction observed in these offspring. This review discusses the impact of such a dietary insult on the vascular function of resistance arteries from pregnant rats (pF 0), their offspring (F 1), the pregnant offspring (pF 1) and the second generation (F 2). At each stage, disturbances in endothelium-dependent relaxation were observed, implicating changes in endothelial nitric oxide (NO)-guanylate cyclase (GC) signalling pathway in the vascular adaptations to pregnancy and the programmed effects on offspring.

Expansion of the humoral effector cell compartment of both systemic and mucosal immune systems in a weanling murine model which duplicates critical features of human protein-energy malnutrition.

A direct comparison of systemic (spleen) and mucosal (intestine) antibody-producing systems was made in weanling male C57BL/6J mice subjected to wasting protein-energy malnutrition (PEM) by means of a low-protein protocol known to duplicate immunological and physiological features of human malnutrition. ELISA revealed low concentrations of biliary and gut lumen immunoglobulin (Ig) A in malnourished mice concomitantly with a high concentration of blood IgA. The low-protein model, therefore, exhibited fidelity to human protein-energy malnutrition in its influence on the concentrations of the mucosal Ig, IgA, in critical biological fluids. The number of IgA-, IgM- and IgG-containing cells was estimated morphometrically on a per organ basis. The low-protein protocol supported expansion in numbers of mucosal IgA-containing cells (18 x relative to a zero-time control group) and of splenic IgG-containing cells (135x), albeit an attenuated expansion in comparison with that of well-nourished control animals (132x and 571x respectively relative to zero-time controls). Up to terminal differentiation of Ig-containing cells, systemic and mucosal antibody-producing systems exhibited similarly remarkable resistance to wasting malnutrition. Epithelial transport of IgA may be an aspect of the mucosal antibody response which is particularly sensitive to PEM.