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Circulating glutamate concentration as a biomarker of visceral obesity and associated metabolic alterations

Circulating glutamate concentration as a biomarker of visceral obesity and associated metabolic alterations

We aimed to determine the ability of glutamate concen- tration to identify individuals with visceral obesity and an altered metabolic profile. We showed that glutamate level was significantly associated with VAT and that it allowed identification of individuals with VAT area ≥ 100 cm 2 and ≥ 130 cm 2 . To this end, the optimal glutamate thresh- old had a greater sensitivity, but a lower specificity than the MetS and the HTW phenotype. Furthermore, women with a high glutamate level had an altered metabolic pro- file, particularly regarding total TG levels and the amount of TG and cholesterol in their VLDLs. To our knowledge, this is the first study focusing on the potential of glutam- ate concentration as a biomarker of VAT accumulation and metabolic alterations.
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Deciphering the role of interleukin-22 in metabolic alterations

Deciphering the role of interleukin-22 in metabolic alterations

IL-22 is a small protein discovered in 2000 by the research group of Renauld [1]. The main producers of IL-22 are CD4+ effector/memory T-cells including T-helper(Th)1-, Th17-, and Th22-cells as well as group 3 innate lymphoid cell (ILC3), the latter comprising natural killer cells, lymphoid tissue inducer like cells, and natural cytotoxicity receptor-positive ILCs [1]. The exact cellular sources of IL-22 in human diseases are often unknown and probably vary depending on the nature of the disorders. While the IL-22 secretion by Th-cells occurs following specific antigenic stimula- tion supported by antigen-presenting cells, IL-22 pro- duction by ILC3 is provoked by cytokines like IL-23, IL-1β, and tumor necrosis factor-α (TNF-α). This is important, because low inflammation is observed in people with adiposity and metabolic alterations and, via these inflammatory mediators, might cause per- manent IL-22 production. IL-22 acts on cells situated
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Metabolic alterations induced by attenuated Zika virus in glioblastoma cells

Metabolic alterations induced by attenuated Zika virus in glioblastoma cells

In addition to metabolic alterations induced by the ZVp over glioblastoma cells, we have also intended to confirm its cytopathic effects over the same cell line and evaluate its potential over several other sorts of tumors. Therefore, we have performed a preliminary anti-proliferative activ- ity test over glioblastomas and eight other different cell lines. This first test confirmed the anti-proliferative effect of the ZVp over GBMs, since it showed 50% of cytostatic effect. Interestingly, the attenuated ZIKV prototype cyto- static effect has also been observed in six other tumors and one immortalized cell lines. Noteworthy, the most affected cell lines were prostate and ovarian tumor cells, where cytostatic effect was most evident. It has been recently observed that ZIKV presents tropism for uro- genital cells [49–51], and our results show that the ZVp presented a similar tropism, even after inactivation by heat. Although prostate and ovarian cells were the most affected, the attenuated ZIKV prototype still presents potential to interfere with other 6 cell lines that have also shown cytostatic effect, mainly glioblastoma, which is the most studied cell line with respect to ZIKV infection.
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Ameliorative effect of tamarind leaf on fluoride-induced metabolic alterations

Ameliorative effect of tamarind leaf on fluoride-induced metabolic alterations

Tamarindus indica L. (Fabaceae; common name: tam- arind) is a multipurpose tropical tree: the leaves, flowers, fruits and seeds are used to make curries, salads, stews and soups in many countries. The tender leaves of T. indica are traditionally used with lentils in Southern India, replacing the tamarind fruit. The leaves are also used to treat throat infections/coughs, fever, intestinal worm infections, uri- nary problems and liver ailments. Leaves and pulp act as a cholagogue, laxative and anticongestant and exhibit anti- oxidant activity in the liver in addition to their blood sugar- reducing properties [22]. The leaf extracts were also shown to be antifungal and antimicrobial [23, 24]. As there are no reports concerning the utility of tamarind leaves against sodium fluoride-induced toxicity, we evaluated the efficacy of tamarind leaves in mitigating fluoride-induced metabolic alterations in carbohydrate, lipid and antioxidant profiles.
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A Study on High Prevalence of Metabolic Alterations (Dyslipidemia, Diabetes Mellitus, Hyperuricemia) in Patients with Primary Sjogren’s Syndrome

A Study on High Prevalence of Metabolic Alterations (Dyslipidemia, Diabetes Mellitus, Hyperuricemia) in Patients with Primary Sjogren’s Syndrome

A few therapeutic agents like thiazolidinediones, metformin, antioxidants and statins might have a potential role for treatment of primary SS in near future. statins have been proved to have a pleotrophic effort apart from their lipid lowering effect. Atorvastatin has a special role with anti- inflammatory and immunomodulatory action in primary SS. Hence it has been proved to have a promising role in the treatment of systemic autoimmune diseases with coexisting metabolic alteration. There have been previous studies suggesting a superior role of immunomodulators (antimalarials) when compared with corticosteroids in the treatment of metabolic alterations in Sjogren s syndrome. Hence it has been suggested to limit the use of corticosteroids in treatment of SS with extraglandular manifestations alone with the least possible dose. When the use of corticosteroid therapy is indicated for a prolonged duration, the supplementation with biological agents or immunomodulators has been advised.
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Systemic and central nervous system metabolic alterations in Alzheimer’s disease

Systemic and central nervous system metabolic alterations in Alzheimer’s disease

In Alzheimer’s disease (AD), glucose hypometabolism is con- sidered a typical feature of the disease at clinical stages, indi- cating the loss of neuronal function in specific brain regions [1]. Cerebral glucose hypometabolism, characterized by im- paired glucose uptake and utilization related to brain insulin resistance [2, 3], and progressive mitochondrial dysfunction with aging [4] have both been recently associated with AD and suggest involvement of energy metabolism alterations in AD pathophysiology. Importantly, these alterations in early AD may occur both at the central nervous system (CNS) and the systemic level and play a role in clinical disease pro- gression [5, 6]. Despite these observations, the extent and sig- nificance of CNS and systemic metabolic alterations in AD remain poorly understood. Therefore, further and in-depth characterization of metabolic alterations to unravel potential new targets for therapeutic intervention is needed. Metabolo- mics is a powerful phenotyping technology, which allows to systematically identify and quantify the active small molecule-metabolite complement of cells, tissues, or biofluids and provide a sensitive and highly specific multiparametric measure of disease phenotype at the molecular level [7–14].
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Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

Metabolic alterations in multiple sclerosis and the impact of vitamin D supplementation

pathways and another incorporating known information on metabolic pathways. For the agnostic approach, we applied WGCNA to identify related metabolite modules (38). WGCNA is a systems biology method that was originally developed to characterize correlation patterns among genes from microarray studies. It has been applied in other settings, such as metabolomics, cancer, and analysis of brain imaging data (39–42). As an analytic technique, its primary goal is to find clusters (modules) of interconnected nodes (e.g., metabolites in this case), and it allows summary measures of the clusters to be used in subsequent analysis. This helps to alleviate some of the multiple testing problems introduced by analyzing hundreds of nodes because module scores are used in the analysis rather than an individ- ual marker. WGCNA can also identify highly connected hub nodes (metabolites), which are centrally located within the module, and prior studies of gene expression have shown that such hub nodes are more likely to be biologically relevant markers. Briefly, WGCNA identifies modules by constructing a correlation network of metabolites and derives eigen-metabolite scores (corresponding to the first prin- cipal component) from the identified modules.
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Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations

Deficiency of metabolic regulator FGFR4 delays breast cancer progression through systemic and microenvironmental metabolic alterations

FGF21 and FGF19 are potent regulators of glucose, lipid and energy metabolic homeostasis and suppress obesity and diabetes through targeting adipose tissue and liver [14,18,20,26]. These metabolic effects occur without a same extent of growth and proliferation-promoting activ- ity characteristic of canonical FGFs such as FGF1 and FGF2 [11,14]. We confirmed our prediction that the breast adipose compartment is also a target of systemic FGF21 [17]. The upregulation of Cpt1, Pck1, PPARα and Ucp1 in addition to adiponectin in breast tissue is consistent with previous studies in the independent adipose tissue and adipocytes, which showed that FGF21 activates the adipose FGFR1-KLB complex leading to significant changes in the expression of these metabolic genes and regulators [18,72]. Therefore, these results support the notion that FGF21 and possibly FGF19/15 as well, are top candi- dates underlying changes in metabolic pathways and concurrent delay of breast cancer development observed here (Figure 9). They not only modulate metabolic path- ways in peripheral fat depots that affect the breast system- ically, but also directly act on breast adipocytes with major microenvironmental impact on mammary epithelial cells during development of mammary tumor. These activities of FGF21 and possibly FGF19 on adipocytes that elicit tumor suppressive metabolic signals appear sufficient to override tumor-promoting effects of elevated bile acids,
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Systemic Immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD)

Systemic Immuno-metabolic alterations in chronic obstructive pulmonary disease (COPD)

The reduction of OCR and ECAR in COPD PBMCs is most likely because of inhibition of enzymes of the glyco- lytic and β-oxidation pathway which may lead to an accu- mulation of the intermediates within the cells. A number of glycolytic enzymes in immune cells are known to per- form non-metabolic functions through signaling and gene regulation that influence the inflammatory response [29]. For eg, GAPDH is known to be translocated to the nu- cleus under conditions of oxidative stress to initiate apop- tosis [30] or induce translation of IFN-γ and IL-2 in T- cells under glucose deprived conditions [31]. Alternative pathways in the cytoplasm may also metabolize glucose such as the pentose phosphate pathway (which is also known to be upregulated under oxidative-stress) and glu- coronic acid pathway. Unutilized or excess fatty acids may uncouple mitochondrial respiration and induce lipotoxi- city if not stored in the form of lipid droplets which act as highly dynamic storage pool of fatty acids to support im- mune cell activation and function. Similarly, unutilized glucose could also be stored as glycogen within the cells. Thus it could be postulated that, impaired immune cell metabolism may drive disease pathophysiology by altering the immune cell function. As is evident from both, in- vitro and in-vivo data; mitochondrial health in immune cells play an important role in the progression of COPD (Fig. 2a, Fig. 4b) and could be considered as the driving force in the development of COPD. As long as the mito- chondria are healthy, the disease progression is impeded as shown in healthy smokers and RAW 264.7 cells ex- posed to 0.1 and 0.25% CSC.
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Fluorescence Monitoring of Mitochondrial Components of Oxidative Phosphorilation of Post-Synaptic Activation in Neocortical Slices in the Mouse

Fluorescence Monitoring of Mitochondrial Components of Oxidative Phosphorilation of Post-Synaptic Activation in Neocortical Slices in the Mouse

These results, although preliminary in nature (these were obtained with a very small number of samples, 3 mice, 3 slices per mouse), do not evidence consistent differences between the two groups of mice in the first part of the response following the electrical stimulus. However, Fig 2 indicates a consistent difference in the second part of the response (overshoot), i.e., in the amplitude, and therefore also in the duration as well. Therefore, we can confirm that metabolic alterations previously showed in the stressed mice model (3) and evidenced as fasting hyperglycemia, probably due in part to unbalance of hypothalamus-pituitary- adrenal hormones, can be responsible for alterations evidenced in the brain of stressed mice as well, . Moreover, according to the present results, in the light of data in the literature, brain alterations can be put in relationship to mitochondrial function: in fact, Shuttleworth et al (7) showed that different glucose concentration in the bath solution may modulate overshoot in different directions. Other possibilities cannot be excluded. For example previous experiments in the literature indicate that modulation of the overshoot component is influenced by drugs which stimulate, or vice-versa inhibit, post-synaptic neuronal excitation, for example bicuculline or ouabain; also changes in the Na+ concentration of ACSF solution may influence the response (7). Neonatal repeated stressful procedures induce alterations of several receptorial families, e.g., those related to the GABA and the opioid systems (see ref (8). Therefore, much experimental work is necessary before giving correct interpretation of our data, and on the role played by receptorial systems in the “overshoot” phenomenon produced in the somatosensorial cortex in our experiments.
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Asiatic acid attenuates renin angiotensin system activation and improves vascular function in high carbohydrate, high fat diet fed rats

Asiatic acid attenuates renin angiotensin system activation and improves vascular function in high carbohydrate, high fat diet fed rats

asiatic acid with its antioxidant and anti-inflammatory activity, improved hemodynamic and metabolic alterations in diet-induced metabolic syndrome [5]. Asiatic acid has also been shown to ameliorate insulin resistance and oxidative stress and reduce inflammatory markers in mice hepatic tissues, resulting in protection from high fat diet-induced hepatic injury [32]. In streptozotocin induced diabetic rats, asiatic acid attenuated hyperlip- idemia and hyperglycemiavia regulating key enzyme in lipid metabolism [33]. Other biological effects of asi- atic acid have been demonstrated. Wang revealed anti- glycative effects of asiatic acid that related to decreasing oxidative stress and inflammation in human keratinocyte cells [34]. Antihypertensive effects of asiatic acid in animal model hypertension has been reported to involve the modulation eNOS/p 47phox protein expression [28].
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Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

Region-specific effects on brain metabolites of hypoxia and hyperoxia overlaid on cerebral ischemia in young and old rats: a quantitative proton magnetic resonance spectroscopy study

It is known that oxidative stress is a relevant mechanism involved in the process of brain aging [4,5]. Moreover, aging is the most important risk factor for neurodegenera- tive disorders, such as Alzheimer and Parkinson's disease [16,17]. Oxidative damage is essential for most neurode- generative diseases [2,3,16,18]. Excessive production of ROS also is germane to the neuronal damage associated with ischemia and brain edema, ranging from metabolic alterations to apoptosis or necrosis [8,19]. Hypoxia and hyperoxia, the former being often a sequel of a disease pro- cess and the latter a treatment modality, act as inducers of ROS formation [6-8]. In the present study, therefore, we set
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New and emerging agents in the management of lipodystrophy in HIV-infected patients

New and emerging agents in the management of lipodystrophy in HIV-infected patients

Factors related to lipodystrophy and metabolic alterations in patients with human immunodeficiency virus infection receiving highly active antiretroviral therapy.. Clin Infect Dis.[r]

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ATHEROSCLEROTIC RISK AMONG EPILEPTIC PATIENTS TAKING CARBAMAZEPINE, PHENYTOIN TREATMENT: BRIEF REVIEW

ATHEROSCLEROTIC RISK AMONG EPILEPTIC PATIENTS TAKING CARBAMAZEPINE, PHENYTOIN TREATMENT: BRIEF REVIEW

Very little data exist regarding the effects of specific AEDs on the incidence of vascular events. One Finnish study found a lower prevalence of ischemic heart disease in epilepsy patients, and furthermore found that patients who were on enzyme-inducing AEDs had 29% lower mortality due to heart disease 15 . When a Norwegian group performed a survey of coronary risk profiles on patients with epilepsy and controls, however, they found no significant differences 16 . It is possible that the Finnish study reflects genetic variants in the isolated, homogeneous Finnish population, as Finnish studies of serologic risk factors also yield different results than those in other populations. This review focuses on risk of atherogenic metabolic alterations, disordered lipid profiles, and increased lipoprotein (a) serum levels among epileptic patients on phenytoin, carbamazepine treatment. Mechanism of Enzyme induction effects on Serum Cholesterol: The enzyme-inducing AEDs phenytoin (PHT), carbamazepine (CBZ), increase the activity of the hepatic cytochrome P450 system, which is involved in synthesis of serum cholesterol. Animal data show that a particular enzyme, CYP51A1, catalyzes the conversion of lanosterol into cholesterol intermediates 17 . When these intermediates build up through inhibition of the enzyme, they in turn inhibit the rate-limiting step of cholesterol synthesis, 3-hydroxy-3-methylglutaryl- coenzyme A reductase, and slow the synthesis of cholesterol 18 .
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Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming

Ionizing Radiation Impairs T Cell Activation by Affecting Metabolic Reprogramming

In connection with the compromised metabolic reprogramming, TCR-induced cell proliferation was also found decreased in T cells exposed to IR. The results showed an apparent halt of proliferation after 3Gy IR exposure, while 0.1Gy or 0.5Gy doses had little effect on TCR-stimulated proliferation measured by CFSE staining (Fig. 2B). Interestingly, results of metabolomics profiling (Fig. 3C, 3D, & 4B) indicate that the metabolic up-regulation in response to TCR stimulation is significantly compromised at a dose of as low as 0.5Gy, whilst at this dose no remarkable effect on proliferation was observed (Supplementary Figure 1). This discrepancy indicates that metabolic reprogramming during T cell activation is rather sen- sitive to radiation damage and there might be a threshold effect of metabolic impairment in order to induce the detectable alterations in other cellular processes, such as proliferation and cytokine produc- tion. Nevertheless, the impaired metabolic modula- tion at the dose range with little effect on T cell pro- liferation, like the one observed in 0.5Gy group of this study, may lead to alteration of T cell function. Inter- estingly, the low dose radiation such as 0.1Gy showed distinct changes from the higher doses as demon- strated in the PCA plot (Fig. 3C) with levels of some metabolites elevated in 0.1Gy rather than decreased in the other tested doses (Fig. 4B). It remains to be de- termined whether these metabolomics changes con- tribute to the widely known stimulatory effect of low dose radiation on immune cells [31, 32]. In this study we took advantage of UPLC-QTOF technique in combination with cell immunology methods to inves- tigate the effects of IR on T cell function. The robust metabolomics approach that elucidates the metabolic alterations is more sensitive than the commonly used cell biology assays and reveals significant changes in
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The ischaemic constellation: an alternative to the ischaemic cascade—implications for the validation of new ischaemic tests

The ischaemic constellation: an alternative to the ischaemic cascade—implications for the validation of new ischaemic tests

Assembling data from experiments that use different possibilities from the three ways of spreading ischaemia intensity on a spectrum relies on the assumption that the three dif- ferent meanings of increasing ischaemia are equivalent. If the ischaemic cascade model is accurate, the order of events should be the same in all three. For example, it might be metabolic alterations fi rst, followed sequen- tially by myocardial perfusion abnormalities, wall motion abnormalities, ECG changes and angina. If this assumption is not correct then we should be much more thoughtful when displaying illustrations of the process of ischaemia.
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Metabolic Syndrome and Perioperative Complications during Scheduled Surgeries with Spinal Anesthesia

Metabolic Syndrome and Perioperative Complications during Scheduled Surgeries with Spinal Anesthesia

Background: Metabolic syndrome (MS) is a constellation of factors associated with increased risk of developing cardiovascular diseases and Diabetes Mellitus. Despite of the many studies related to MS, little is known about its impact on scenarios such as surgical anesthesia. Objective: To ex- amine the correlation between demographic and metabolic variables with the occurrence of pe- rioperative complications in patients with MS undergoing scheduled surgeries using a spinal anesthesia technique in the surgery department at the University Clinic San Juan de Dios in Carta- gena de Indias, Colombia. Methods: Observational, analytical, cross-sectional, single-center study of 150 subjects with MS and 150 control subjects. Perioperative complications, socio-demographic, hemodynamic and respiratory variables were registered. Groups were compared using t test, Fisher’s exact test or Chi-square, as appropriate. We applied a logistic multiple regression model, adjusted by backward stepwise at 0.25 and forward at 0.05, to find possible incompatible associa- tions. p value < 0.05 was considered significant. Results: There were significant differences be- tween groups in age, American Society of Anesthesiologists physical status classification, frequen- cy of diseases associated to MS and perioperative complications. There were no cases of mortality among patients. There was statistically significant difference between the two groups for intra- operative hypotension and hypertension with p values of <0.0001 and 0.034. Among postopera- tive complications there was statistically significant difference in pain (13.3% vs 5.3% in patients without MS) and nausea and/or postoperative vomiting (8% vs 2% in patients without MS) with a
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Serum calcium and phosphate level alterations in metabolic syndrome

Serum calcium and phosphate level alterations in metabolic syndrome

this syndrome (Bucher et al., 1996). Parathyroid hormone increases intracellular calcium by stimulating calcium channels and thus influence insulin sensitivity and blood pressure. Increased serum calcium concentration has been found to be associated with high blood pressure, impaired glucose tolerance, and dyslipidemia. Also increased serum calcium concentration has been described as a feature of the metabolic syndrome. Haglin presented a hypothesis in 2001 suggesting that low serum phosphate is the cause of the disturbed metabolism in the metabolic syndrome (Haglin, 2001). This was based on the fact that serum phosphate is an important component of energy metabolism (Grundy et al., 2005; Malik and Razig, 2008). Reduction of serum phosphate levels could therefore theoretically contribute to the pathogenesis of the syndrome by leading to disturbances in energy metabolism resulting in insulin resistance, hyperglycemia, disturbed lipid metabolism, increased weight, and hypertension. It was suggested for the first time in 1926 that hypophosphatemia might contribute to impaired glucose tolerance (Lind et al., 1988). More recently, hypophosphatemia has been linked to impaired glucose utilization, insulin resistance, and hyperinsulinemia (Bucher et al., 1996; Lind et al., 1988; Fardella and Rodriguez-Portales, 1995) in patients with the metabolic syndrome; a negative correlation between serum phosphate and body mass index (BMI) has been observed (Kim et al., 2008; Wang et al. 2008). Recent studies shows that the phosphate is involved directly in carbohydrate metabolism: hypophosphatemia can result in impaired utilization of glucose, insulin resistance, and hyperinsulinemia (Dobnig et al., 2008). So, reduced phosphate levels may contribute directly to the development of the obesity, hypertension, and dyslipidemia that characterize metabolic syndrome. The aim of the present study is to investigate the relation of calcium, phosphate levels with the characteristics of metabolic syndrome, as well as the mechanism that may be responsible for alterations in serum calcium and phosphate level in patients with this syndrome.
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Impacts of Ambient Temperature and Humidity on Biochemical Traits in Male Rabbits Fed Dietary Protein and Selenium Supplementation

Impacts of Ambient Temperature and Humidity on Biochemical Traits in Male Rabbits Fed Dietary Protein and Selenium Supplementation

Cortisol concentrations differed significantly between the three dietary proteins with high level at 18g/100g as compared to other dietary levels. Although no particular trend observed. However, it has been shown that low protein diets could elicit certain physiological stress in both human and animals, due to metabolic demand for amino acids to maintain nitrogen balance for the body system [23], and sustenance of normal body functions. As such, this biological response could be responsible for the increased cortisol levels when the level of dietary protein is low, and vice versa. In addition, it has been shown that adequate protein intake and utilization may enhance normal hormonal and enzymatic secretions or functions, with consequent optimum metabolic functions in rabbits[5]. Hence, there may be very low levels of cortisol in body circulation of group of animal under high protein dietary treatment, due to absence of stress. However, cortisol concentration was also affected by period, but there may be possible increase in metabolic heat in the body, as dietary protein level has been shown to enhance the production of metabolic heat in the body[26]. Therefore feeding protein diets at appropriate levels may be an important aspect of dietary modification in controlling stressful conditions in animals.
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