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Scientific Reports Jun 2021To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and...
To study, in young growing rats, the consequences of different levels of dietary protein deficiency on food intake, body weight, body composition, and energy balance and to assess the role of FGF21 in the adaptation to a low protein diet. Thirty-six weanling rats were fed diets containing 3%, 5%, 8%, 12%, 15% and 20% protein for three weeks. Body weight, food intake, energy expenditure and metabolic parameters were followed throughout this period. The very low-protein diets (3% and 5%) induced a large decrease in body weight gain and an increase in energy intake relative to body mass. No gain in fat mass was observed because energy expenditure increased in proportion to energy intake. As expected, Fgf21 expression in the liver and plasma FGF21 increased with low-protein diets, but Fgf21 expression in the hypothalamus decreased. Under low protein diets (3% and 5%), the increase in liver Fgf21 and the decrease of Fgf21 in the hypothalamus induced an increase in energy expenditure and the decrease in the satiety signal responsible for hyperphagia. Our results highlight that when dietary protein decreases below 8%, the liver detects the low protein diet and responds by activating synthesis and secretion of FGF21 in order to activate an endocrine signal that induces metabolic adaptation. The hypothalamus, in comparison, responds to protein deficiency when dietary protein decreases below 5%.
Topics: Animals; Diet, Protein-Restricted; Disease Models, Animal; Energy Intake; Energy Metabolism; Fibroblast Growth Factors; Humans; Hypothalamus; Liver; Male; Protein Deficiency; Rats; Satiety Response
PubMed: 34127689
DOI: 10.1038/s41598-021-91274-4 -
Asia Pacific Journal of Clinical... 2020Lean body mass (LBM) agglomerates the bulk of nitrogen (N)-containing molecules following well-identified age and sex evolutionary patterns best appraised in clinical... (Review)
Review
Lean body mass (LBM) agglomerates the bulk of nitrogen (N)-containing molecules following well-identified age and sex evolutionary patterns best appraised in clinical practice using the serial measurement of plasma transthyretin (TTR). Methionine (Met), the sole essential amino acid bearing a sulfur (S) atom, presides at the initiation of protein synthesis while maintaining stable body tissue S:N molar ratios of approximately 1:14.5. In protein- depleted states, N- and Met-deficiencies operate as limiting factors for LBM protein synthesis and accretion, causing growth retardation and subnormal TTR plasma values. In inflammatory disorders, LBM is subjected to cytokine-induced tissue breakdown reflecting the S:N ratio found in healthy tissues whereas the liver secretion of TTR declines in proportion. Both malnutrition and inflammation are characterized by stepwise LBM downsizing and reduced bioavailability of Met body stores setting in motion molecular mechanisms safeguarding Met homeostasis at the expense of augmented homocysteine (Hcy) values in biological fluids. Divergent TTR and Hcy alterations indicate that rising Hcy values measured in plasma and cerebrospinal fluid should be regarded as the dark side of efficient compensatory processes. As a result, the neuroprotective activities normally exerted by TTR are weakened, whereas the oxidative burden generated by supranormal Hcy concentrations are strengthened. The combination of protein malnutrition and inflammatory disorders of any cause maximizes the risk of incurable neurodegenerative effects.
Topics: Alzheimer Disease; Energy Metabolism; Humans; Inflammation; Protein Deficiency
PubMed: 32990603
DOI: 10.6133/apjcn.202009_29(3).0002 -
Asian Pacific Journal of Cancer... Sep 2023This study aimed to analyze the correlation between the 3-year disease-free survival (DFS) and mismatch repair (MMR) protein levels in patients with type 1 endometrial... (Observational Study)
Observational Study
BACKGROUND
This study aimed to analyze the correlation between the 3-year disease-free survival (DFS) and mismatch repair (MMR) protein levels in patients with type 1 endometrial carcinoma. Many studies have reported different results regarding the role of MMR in the prognosis of endometrial carcinoma; therefore, we aimed to identify this association in our hospital.
METHODS
This observational study employed a historical cohort design and included patients with type 1 endometrial carcinoma who underwent surgery at Dr. Soetomo Hospital between January 2017 and December 2019. Medical records and paraffin blocks meeting these criteria were obtained. MMR proteins (MLH1 and MSH2) were assessed using immunohistochemistry.
RESULTS
A total of 46 patients with type 1 endometrial carcinoma were analyzed. We observed MMR deficiency (dMMR) in 12 patients (26.1%) and MMR proficiency (pMMR) in 34 patients (73.9%). Of the 12 patients with dMMR, nine cases (75%) were diagnosed as stage I and 7 (58.33%) as low grade. The 3-year DFS in patients with dMMR and pMMR was 83.3% and 67.6%, respectively (Hazard Ratio 2.31, 95% CI 0.5135-10.475, p=0.27). Higher stages had a 5.42 times increased risk of recurrence (95% CI 1.3378-21.9358, p=0.018). Higher histopathological grades were also associated with 8.65 times increased risk of recurrence (95% CI 2.5020-29.8738, p=0.001).
CONCLUSION
Patients with dMMR had a better DFS compared to those with pMMR; however, the difference was not statistically significant. The tumor stage and histopathological grade were independent risk factors for recurrence.
Topics: Female; Humans; Disease-Free Survival; DNA Mismatch Repair; Retrospective Studies; Colorectal Neoplasms; Endometrial Neoplasms; Protein Deficiency; MutL Protein Homolog 1; Mismatch Repair Endonuclease PMS2
PubMed: 37774076
DOI: 10.31557/APJCP.2023.24.9.3229 -
Frontiers in Nutrition 2020Nutritional epidemiology shows that insufficient protein intake is related to senile dementia. The levels of protein intake in aged people are positively associated with...
Nutritional epidemiology shows that insufficient protein intake is related to senile dementia. The levels of protein intake in aged people are positively associated with memory function, and elderly people with high protein intake have a low risk of mild cognitive impairment. Although the beneficial roles of protein nutrition in maintaining brain function in aged people are well demonstrated, little is known about the mechanism by which dietary intake of protein affects memory and brain conditions. We fed aged mice a low protein diet (LPD) for 2 months, which caused behavioral abnormalities, and examined the nutritional effect of essential amino acid administration under LPD conditions. The passive avoidance test revealed that LPD mice demonstrated learning and memory impairment. Similarly, the LPD mice showed agitation and hyperactive behavior in the elevated plus maze test. Moreover, LPD mice exhibited decreased concentrations of gamma-aminobutyric acid (GABA), glutamate, glycine, dopamine, norepinephrine, serotonin and aspartate in the brain. Interestingly, oral administration of seven essential amino acids (EAAs; valine, leucine, isoleucine, lysine, phenylalanine, histidine, and tryptophan) to LPD mice, which can be a source of neurotransmitters, reversed those behavioral changes. The oral administration of EAAs restored the brain concentration of glutamate, which is involved in learning and memory ability and may be associated with the observed behavioral changes. Although the details of the link between decreased amino acid and neurotransmitter concentrations and behavioral abnormalities must be examined in future studies, these findings suggest the importance of dietary protein and essential amino acids for maintaining brain function.
PubMed: 32219097
DOI: 10.3389/fnut.2020.00023 -
Annals of Translational Medicine Sep 2018Hereditary spherocytosis (HS) belongs to the group of congenital hemolytic anemias resulting from plasma membrane protein deficiency. When diagnosed too late, HS bares... (Review)
Review
Hereditary spherocytosis (HS) belongs to the group of congenital hemolytic anemias resulting from plasma membrane protein deficiency. When diagnosed too late, HS bares the risk of long-term complications including gall stones and severe anemia. Here, there are discussed advances in HS screening and diagnostics, with a particular focus on methodologies, most of which are available in clinical laboratories worldwide.
PubMed: 30306078
DOI: 10.21037/atm.2018.07.35 -
World Journal of Clinical Cases Jul 2021Patients with lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency have a variety of clinical symptoms, but there is no apparent...
BACKGROUND
Patients with lipopolysaccharide (LPS)-responsive beige-like anchor protein (LRBA) deficiency have a variety of clinical symptoms, but there is no apparent genotype-phenotype correlation, and patients carrying the same mutations may have different phenotypes. Therefore, it is not easy for doctors to make a decision regarding hematopoietic stem cell transplantation (HSCT) for LRBA-deficient patients. We hypothesized that there may be a protein-phenotype correlation to indicate HSCT for LRBA-deficient patients.
AIM
To report on three Chinese LRBA-deficient patients and determine the correlation between residual protein expression and disease phenotypes
METHODS
Clinical data of three Chinese LRBA-deficient patients were collected, and protein levels were detected by Western blot analysis. In addition, LRBA mutation information of another 83 previously reported patients was summarized.
RESULTS
All the major clinical findings indicated enteropathy, but patients 1 and 3 presented with more severe symptoms than patient 2. Endoscopy and histology indicated nonspecific colitis for patients 1 and 3 but Crohn's disease-like colitis for patient 2. Compound heterozygous mutations in LRBA were found in patient 1, and homozygous mutations in LRBA were found in patient 2 and patient 3. Only patient 2 responded well to traditional immunosuppressive treatment. Residual expression of the LRBA protein in patients 1 and 3 was very low, but in patient 2, a more than 0.5-fold in expression of the LRBA protein was found compared to that in the control. After HSCT, patient 1 had increased LRBA protein expression. We summarized the genetic information of 86 patients, and the mutations in patients 1 and 3 were novel mutations.
CONCLUSION
We described three Chinese LRBA-deficient patients, two of whom carried novel mutations. These patients had no genotype-phenotype correlations, but their residual LRBA protein expression might be associated with disease outcome and could be an indicator for HSCT.
PubMed: 34368306
DOI: 10.12998/wjcc.v9.i21.5873 -
The American Journal of Clinical... Nov 2016Environmental enteropathy, which is linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide....
BACKGROUND
Environmental enteropathy, which is linked to undernutrition and chronic infections, affects the physical and mental growth of children in developing areas worldwide. Key to understanding how these factors combine to shape developmental outcomes is to first understand the effects of nutritional deficiencies on the mammalian system including the effect on the gut microbiota.
OBJECTIVE
We dissected the nutritional components of environmental enteropathy by analyzing the specific metabolic and gut-microbiota changes that occur in weaned-mouse models of zinc or protein deficiency compared with well-nourished controls.
DESIGN
With the use of a H nuclear magnetic resonance spectroscopy-based metabolic profiling approach with matching 16S microbiota analyses, the metabolic consequences and specific effects on the fecal microbiota of protein and zinc deficiency were probed independently in a murine model.
RESULTS
We showed considerable shifts within the intestinal microbiota 14-24 d postweaning in mice that were maintained on a normal diet (including increases in Proteobacteria and striking decreases in Bacterioidetes). Although the zinc-deficient microbiota were comparable to the age-matched, well-nourished profile, the protein-restricted microbiota remained closer in composition to the weaned enterotype with retention of Bacteroidetes. Striking increases in Verrucomicrobia (predominantly Akkermansia muciniphila) were observed in both well-nourished and protein-deficient mice 14 d postweaning. We showed that protein malnutrition impaired growth and had major metabolic consequences (much more than with zinc deficiency) that included altered energy, polyamine, and purine and pyrimidine metabolism. Consistent with major changes in the gut microbiota, reductions in microbial proteolysis and increases in microbial dietary choline processing were observed.
CONCLUSIONS
These findings are consistent with metabolic alterations that we previously observed in malnourished children. The results show that we can model the metabolic consequences of malnutrition in the mouse to help dissect relevant pathways involved in the effects of undernutrition and their contribution to environmental enteric dysfunction.
Topics: Animals; DNA, Bacterial; Diet; Dietary Proteins; Feces; Gastrointestinal Microbiome; Gastrointestinal Tract; Lipocalin-2; Male; Malnutrition; Metabolomics; Mice; Mice, Inbred C57BL; Peroxidase; Protein Deficiency; RNA, Ribosomal, 16S; Sequence Analysis, DNA; Weaning; Zinc
PubMed: 27733402
DOI: 10.3945/ajcn.116.131797 -
Pediatric Nephrology (Berlin, Germany) Feb 2021Some children with declining height and BMI SDS fail to respond to optimisation of nutritional intake. As well as poor growth, they have muscle wasting and relative... (Review)
Review
Some children with declining height and BMI SDS fail to respond to optimisation of nutritional intake. As well as poor growth, they have muscle wasting and relative preservation of body fat. This is termed protein energy wasting (PEW). The process results from an interaction of chronic inflammation alongside poor nutritional intake. This review discusses the causes and potential preventative therapies for PEW.
Topics: Cachexia; Child; Eating; Humans; Nutritional Status; Protein-Energy Malnutrition; Renal Dialysis; Renal Insufficiency, Chronic
PubMed: 31834488
DOI: 10.1007/s00467-019-04424-2 -
Cellular Physiology and Biochemistry :... Mar 2021Hereditary Spherocytosis (HS) is the most common erythrocyte membrane disorder causing hemolytic anemia. The wide heterogeneity of both clinical and laboratory... (Clinical Trial)
Clinical Trial
BACKGROUND/AIMS
Hereditary Spherocytosis (HS) is the most common erythrocyte membrane disorder causing hemolytic anemia. The wide heterogeneity of both clinical and laboratory manifestations of HS contributes to difficulties associated with the diagnosis of this disorder. Although massive data previously reported worldwide, there is yet no data on HS among the Tunisian population. Here we aim to characterize HS in Tunisian patients at biochemical and cellular levels, identify the membrane protein deficiency, and compare the accuracy of the diagnostic tests to identify the most appropriate assay for HS diagnosis.
METHODS
We investigated 81 patients with hemolytic anemia and 167 normal controls. The exploration of HS based on clinical and family history, physical examination, and the results of laboratory tests: blood smear, osmotic fragility test (OFT), cryohemolysis test (CT), pink test (PT), eosine-5'-maleimide (EMA) test, and erythrocyte membrane protein electrophoresis.
RESULTS
We identified 21 patients with HS, classified as severe (6/21;28.5%), moderate (10/21;47.6%), and mild (5/21;23.8%). The most prevalent protein deficiency was the band 3 protein detected in ten Tunisian HS patients. The EMA test showed a high specificity (97.5%) and sensitivity (94.7%) for HS diagnosis compared to the other screening tests. Interestingly, fourteen among sixteen patients presenting with homozygous sickle cells HbSS showed an increase of EMA fluorescence intensity compared to other anemic patients.
CONCLUSION
Our study highlights the efficiency of the EMA dye for the detection of HS whatever the nature of the involved protein deficiency. We report for the first time, the most prevalent protein deficiency among Tunisians with HS. Moreover, we found that the combination of the EMA-binding test with PT or incubated OFT improves the diagnosis sensitivity while maintaining a good specificity.
Topics: Adolescent; Adult; Child; Child, Preschool; Eosine Yellowish-(YS); Erythrocyte Membrane; Female; Flow Cytometry; Humans; Infant; Male; Membrane Proteins; Osmotic Fragility; Proteomics; Spherocytosis, Hereditary; Tunisia
PubMed: 33667330
DOI: 10.33594/000000333 -
Oncotarget Apr 2017Cancer patients often experience weight loss caused by protein calorie malnutrition (PCM) during the course of the disease or treatment. PCM is expressed as severe if... (Review)
Review
Cancer patients often experience weight loss caused by protein calorie malnutrition (PCM) during the course of the disease or treatment. PCM is expressed as severe if the patient has two or more of the following characteristics: obvious significant muscle wasting, loss of subcutaneous fat; nutritional intake of <50% of recommended intake for 2 weeks or more; bedridden or otherwise significantly reduced functional capacity; weight loss of >2% in 1 week, 5% in 1 month, or 7.5% in 3 months. Cancer anorexia-cachexia syndrome (CACS) is a multifactorial condition of advanced PCM associated with underlying illness (in this case cancer) and is characterized by loss of muscle with or without loss of fat mass. Cachexia is defined as weight loss of more than 5% of body weight in 12 months or less in the presence of chronic disease. Hence with a chronic illness on board even a small amount of weight loss can open the door to cachexia. These nutritional challenges can lead to severe morbidity and mortality in cancer patients. In the clinic, the application of personalized medicine and the ability to withstand the toxic effects of anti-cancer therapies can be optimized when the patient is in nutritional homeostasis and is free of anorexia and cachexia. Routine assessment of nutritional status and appropriate intervention are essential components of the effort to alleviate effects of malnutrition on quality of life and survival of patients.
Topics: Animals; Anorexia; Cachexia; Energy Metabolism; Humans; Neoplasms; Nutritional Status; Precision Medicine; Protein-Energy Malnutrition
PubMed: 28177923
DOI: 10.18632/oncotarget.15103