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Nature Jul 2023In metazoan organisms, cell competition acts as a quality control mechanism to eliminate unfit cells in favour of their more robust neighbours. This mechanism has the...
In metazoan organisms, cell competition acts as a quality control mechanism to eliminate unfit cells in favour of their more robust neighbours. This mechanism has the potential to be maladapted, promoting the selection of aggressive cancer cells. Tumours are metabolically active and are populated by stroma cells, but how environmental factors affect cancer cell competition remains largely unknown. Here we show that tumour-associated macrophages (TAMs) can be dietarily or genetically reprogrammed to outcompete MYC-overexpressing cancer cells. In a mouse model of breast cancer, MYC overexpression resulted in an mTORC1-dependent 'winner' cancer cell state. A low-protein diet inhibited mTORC1 signalling in cancer cells and reduced tumour growth, owing unexpectedly to activation of the transcription factors TFEB and TFE3 and mTORC1 in TAMs. Diet-derived cytosolic amino acids are sensed by Rag GTPases through the GTPase-activating proteins GATOR1 and FLCN to control Rag GTPase effectors including TFEB and TFE3. Depletion of GATOR1 in TAMs suppressed the activation of TFEB, TFE3 and mTORC1 under the low-protein diet condition, causing accelerated tumour growth; conversely, depletion of FLCN or Rag GTPases in TAMs activated TFEB, TFE3 and mTORC1 under the normal protein diet condition, causing decelerated tumour growth. Furthermore, mTORC1 hyperactivation in TAMs and cancer cells and their competitive fitness were dependent on the endolysosomal engulfment regulator PIKfyve. Thus, noncanonical engulfment-mediated Rag GTPase-independent mTORC1 signalling in TAMs controls competition between TAMs and cancer cells, which defines a novel innate immune tumour suppression pathway that could be targeted for cancer therapy.
Topics: Animals; Mice; Amino Acids; Basic Helix-Loop-Helix Leucine Zipper Transcription Factors; Cell Competition; Cellular Reprogramming Techniques; Dietary Proteins; Disease Models, Animal; GTP Phosphohydrolases; Lysosomes; Mechanistic Target of Rapamycin Complex 1; Neoplasms; Proto-Oncogene Proteins c-myc; Tumor-Associated Macrophages; Immunity, Innate
PubMed: 37380769
DOI: 10.1038/s41586-023-06256-5 -
The Journal of Experimental Medicine Aug 2023The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4+ T cells. Combining antigenically defined diets with gnotobiotic...
The intestinal immune system must tolerate food antigens to avoid allergy, a process requiring CD4+ T cells. Combining antigenically defined diets with gnotobiotic models, we show that food and microbiota distinctly influence the profile and T cell receptor repertoire of intestinal CD4+ T cells. Independent of the microbiota, dietary proteins contributed to accumulation and clonal selection of antigen-experienced CD4+ T cells at the intestinal epithelium, imprinting a tissue-specialized transcriptional program including cytotoxic genes on both conventional and regulatory CD4+ T cells (Tregs). This steady state CD4+ T cell response to food was disrupted by inflammatory challenge, and protection against food allergy in this context was associated with Treg clonal expansion and decreased proinflammatory gene expression. Finally, we identified both steady-state epithelium-adapted CD4+ T cells and tolerance-induced Tregs that recognize dietary antigens, suggesting that both cell types may be critical for preventing inappropriate immune responses to food.
Topics: CD4-Positive T-Lymphocytes; Intestines; T-Lymphocytes, Regulatory; Immune Tolerance; Antigens; Dietary Proteins
PubMed: 37191720
DOI: 10.1084/jem.20221816 -
European Journal of Nutrition Aug 2023Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI)... (Review)
Review
PURPOSE
Changes in dietary protein intake metabolically affect kidney functions. However, knowledge on potential adverse consequences of long-term higher protein intake (HPI) for kidney health is lacking. To summarise and evaluate the available evidence for a relation between HPI and kidney diseases, an umbrella review of systematic reviews (SR) was conducted.
METHODS
PubMed, Embase and Cochrane Database of SRs published until 12/2022 were searched for the respective SRs with and without meta-analyses (MA) of randomised controlled trials or cohort studies. For assessments of methodological quality and of outcome-specific certainty of evidence, a modified version of AMSTAR 2 and the NutriGrade scoring tool were used, respectively. The overall certainty of evidence was assessed according to predefined criteria.
RESULTS
Six SRs with MA and three SRs without MA on various kidney-related outcomes were identified. Outcomes were chronic kidney disease, kidney stones and kidney function-related parameters: albuminuria, glomerular filtration rate, serum urea, urinary pH and urinary calcium excretion. Overall certainty of evidence was graded as 'possible' for stone risk not to be associated with HPI and albuminuria not to be elevated through HPI (above recommendations (> 0.8 g/kg body weight/day)) and graded as 'probable' or 'possible' for most other kidney function-related parameters to be physiologically increased with HPI.
CONCLUSION
Changes of the assessed outcomes may have reflected mostly physiological (regulatory), but not pathometabolic responses to higher protein loads. For none of the outcomes, evidence was found that HPI does specifically trigger kidney stones or diseases. However, for potential recommendations long-term data, also over decades, are required.
Topics: Humans; Albuminuria; Dietary Proteins; Systematic Reviews as Topic; Kidney Calculi; Nutritional Status
PubMed: 37133532
DOI: 10.1007/s00394-023-03143-7 -
Journal of the International Society of... Dec 2024Protein supplementation often refers to increasing the intake of this particular macronutrient through dietary supplements in the form of powders, ready-to-drink shakes,... (Review)
Review
Protein supplementation often refers to increasing the intake of this particular macronutrient through dietary supplements in the form of powders, ready-to-drink shakes, and bars. The primary purpose of protein supplementation is to augment dietary protein intake, aiding individuals in meeting their protein requirements, especially when it may be challenging to do so through regular food (i.e. chicken, beef, fish, pork, etc.) sources alone. A large body of evidence shows that protein has an important role in exercising and sedentary individuals. A PubMed search of "protein and exercise performance" reveals thousands of publications. Despite the considerable volume of evidence, it is somewhat surprising that several persistent questions and misconceptions about protein exist. The following are addressed: 1) Is protein harmful to your kidneys? 2) Does consuming "excess" protein increase fat mass? 3) Can dietary protein have a harmful effect on bone health? 4) Can vegans and vegetarians consume enough protein to support training adaptations? 5) Is cheese or peanut butter a good protein source? 6) Does consuming meat (i.e., animal protein) cause unfavorable health outcomes? 7) Do you need protein if you are not physically active? 8) Do you to consume protein ≤ 1 hour following resistance training sessions to create an anabolic environment in skeletal muscle? 9) Do endurance athletes need additional protein? 10) Does one need protein supplements to meet the daily requirements of exercise-trained individuals? 11) Is there a limit to how much protein one can consume in a single meal? To address these questions, we have conducted a thorough scientific assessment of the literature concerning protein supplementation.
Topics: Humans; Dietary Proteins; Physical Endurance; Exercise; Dietary Supplements; Muscle, Skeletal
PubMed: 38626029
DOI: 10.1080/15502783.2024.2341903 -
Advances in Nutrition (Bethesda, Md.) Jul 2023The effects of supplementation with whey protein alone or with vitamin D on sarcopenia-related outcomes in older adults are unclear. We aimed to assess the effect of... (Meta-Analysis)
Meta-Analysis Review
The effects of supplementation with whey protein alone or with vitamin D on sarcopenia-related outcomes in older adults are unclear. We aimed to assess the effect of whey protein supplementation alone or with vitamin D on lean mass (LM), strength, and function in older adults with or without sarcopenia or frailty. We searched PubMed, Web of Science, and SCOPUS databases. Randomized controlled trials (RCT) that investigated the effect of whey protein supplementation with or without vitamin D on sarcopenia outcomes in healthy and sarcopenic or frail older adults were included. Standardized mean differences (SMDs) were calculated for LM, muscle strength, and physical function data. The analysis showed that whey protein supplementation had no effect on LM and muscle strength; nevertheless, a significant improvement was found in physical function (SMD = 0.561; 95% confidence interval [CIs]: 0.256, 0.865, n = 33), particularly gait speed (GS). On the contrary, whey protein supplementation significantly improved LM (SMD = 0.982; 95% CI: 0.228, 1.736; n = 11), appendicular lean mass and physical function (SMD = 1.211; 95% CI: 0.588, 1.834; n = 16), and GS in sarcopenic/frail older adults. By contrast, co-supplementation with vitamin D enhanced LM gains (SMD =0.993; 95% CI: 0.112, 1.874; n = 11), muscle strength (SMD =2.005; 95% CI: 0.975, 3.035; n = 11), and physical function (SMD = 3.038; 95% CI: 2.196, 3.879; n = 18) significantly. Muscle strength and physical function improvements after whey protein supplementation plus vitamin D were observed without resistance exercise (RE) and short study duration subgroups. Moreover, the combination of whey protein and vitamin D with RE did not enhance the effect of RE. Whey protein supplementation improved LM and function in sarcopenic/frail older adults but had no positive effect in healthy older persons. By contrast, our meta-analysis showed that co-supplementation with whey protein and vitamin D is effective, particularly in healthy older adults, which is likely owing, we propose, to the correction of vitamin D insufficiency or deficiency. The trial was registered at https://inplasy.com as INPLASY202240167.
Topics: Humans; Aged; Aged, 80 and over; Sarcopenia; Vitamin D; Whey Proteins; Dietary Supplements; Vitamins; Muscle Strength; Muscle, Skeletal; Randomized Controlled Trials as Topic
PubMed: 37196876
DOI: 10.1016/j.advnut.2023.05.011 -
Nutrients Aug 2023To determine the effectiveness of whey protein (WP) supplementation during resistance exercise training (RET) vs. RET with or without placebo supplementation on skeletal... (Meta-Analysis)
Meta-Analysis Review
Effectiveness of Whey Protein Supplementation during Resistance Exercise Training on Skeletal Muscle Mass and Strength in Older People with Sarcopenia: A Systematic Review and Meta-Analysis.
OBJECTIVE
To determine the effectiveness of whey protein (WP) supplementation during resistance exercise training (RET) vs. RET with or without placebo supplementation on skeletal muscle mass, strength, and physical performance in older people with Sarcopenia.
METHODS
Electronic searches in the PubMed, Embase, Scopus, Web of Science, LILACS, SPORTDiscus, Epistemonikos, and CINAHL databases were performed until 20 January 2023. Randomized clinical trials conducted on sarcopenic adults aged 60 or older were included. The studies had to compare the effectiveness of the addition of supplements based on concentrated, isolated, or hydrolyzed whey protein during RET and compare it with RET with or without placebo supplementation on skeletal muscle mass and strength changes. The study selection process, data extraction, and risk of bias assessment were carried out by two independent reviewers.
RESULTS
Seven randomized clinical trials (591 participants) were included, and five of them provided data for quantitative synthesis. The overall pooled standardized mean difference (SMD) estimate showed a small effect size in favor of RET plus WP for skeletal muscle mass according to appendicular muscle index, with statistically significant differences compared with RET with or without the placebo group (SMD = 0.24; 95% CI, 0.05 to 0.42; = 0.01; = 0%, = 0.42). The overall pooled mean difference (MD) estimate showed a significant difference of +2.31 kg (MD = 2.31 kg; 95% CI, 0.01 to 4.6; = 0.05; = 81%, < 0.001) in handgrip strength in the RET plus WP group compared with the RET group with or without placebo. The narrative synthesis revealed discordance between the results of the studies on physical performance.
CONCLUSIONS
WP supplementation during RET is more effective in increasing handgrip strength and skeletal muscle mass in older people with Sarcopenia compared with RET with or without placebo supplementation. However, the effect sizes were small, and the MD did not exceed the minimally important clinical difference. The quality of the evidence was low to very low according, to the GRADE approach. Further research is needed in this field.
Topics: Adult; Humans; Aged; Sarcopenia; Whey Proteins; Muscle Strength; Muscle, Skeletal; Hand Strength; Resistance Training; Dietary Supplements
PubMed: 37571361
DOI: 10.3390/nu15153424 -
Sports Medicine (Auckland, N.Z.) Jul 2023Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Casein protein ingestion prior to sleep has been shown to increase myofibrillar protein synthesis rates during overnight sleep. It remains to be assessed whether pre-sleep protein ingestion can also increase mitochondrial protein synthesis rates. Though it has been suggested that casein protein may be preferred as a pre-sleep protein source, no study has compared the impact of pre-sleep whey versus casein ingestion on overnight muscle protein synthesis rates.
OBJECTIVE
We aimed to assess the impact of casein and whey protein ingestion prior to sleep on mitochondrial and myofibrillar protein synthesis rates during overnight recovery from a bout of endurance-type exercise.
METHODS
Thirty-six healthy young men performed a single bout of endurance-type exercise in the evening (19:45 h). Thirty minutes prior to sleep (23:30 h), participants ingested 45 g of casein protein, 45 g of whey protein, or a non-caloric placebo. Continuous intravenous L-[ring-C]-phenylalanine infusions were applied, with blood and muscle tissue samples being collected to assess overnight mitochondrial and myofibrillar protein synthesis rates.
RESULTS
Pooled protein ingestion resulted in greater mitochondrial (0.087 ± 0.020 vs 0.067 ± 0.016%·h, p = 0.005) and myofibrillar (0.060 ± 0.014 vs 0.047 ± 0.011%·h, p = 0.012) protein synthesis rates when compared with placebo. Casein and whey protein ingestion did not differ in their capacity to stimulate mitochondrial (0.082 ± 0.019 vs 0.092 ± 0.020%·h, p = 0.690) and myofibrillar (0.056 ± 0.009 vs 0.064 ± 0.018%·h, p = 0.440) protein synthesis rates.
CONCLUSIONS
Protein ingestion prior to sleep increases both mitochondrial and myofibrillar protein synthesis rates during overnight recovery from exercise. The overnight muscle protein synthetic response to whey and casein protein does not differ.
CLINICAL TRIAL REGISTRATION
NTR7251 .
Topics: Male; Humans; Caseins; Whey Proteins; Dietary Proteins; Sleep; Muscle Proteins; Mitochondrial Proteins; Eating; Muscle, Skeletal
PubMed: 36857005
DOI: 10.1007/s40279-023-01822-3 -
Medicine and Science in Sports and... Oct 2023Protein ingestion during recovery from exercise has been reported to augment myofibrillar protein synthesis rates, without increasing muscle connective protein synthesis... (Randomized Controlled Trial)
Randomized Controlled Trial
INTRODUCTION
Protein ingestion during recovery from exercise has been reported to augment myofibrillar protein synthesis rates, without increasing muscle connective protein synthesis rates. It has been suggested that collagen protein may be effective in stimulating muscle connective protein synthesis. The present study assessed the capacity of both whey and collagen protein ingestion to stimulate postexercise myofibrillar and muscle connective protein synthesis rates.
METHODS
In a randomized, double-blind, parallel design, 45 young male ( n = 30) and female ( n = 15) recreational athletes (age, 25 ± 4 yr; body mass index, 24.1 ± 2.0 kg·m -2 ) were selected to receive primed continuous intravenous infusions with l -[ring- 13 C 6 ]-phenylalanine and l -[3,5- 2 H 2 ]-tyrosine. After a single session of resistance type exercise, subjects were randomly allocated to one of three groups ingesting either 30 g whey protein (WHEY, n = 15), 30 g collagen protein (COLL, n = 15) or a noncaloric placebo (PLA, n = 15). Blood and muscle biopsy samples were collected over a subsequent 5-h recovery period to assess both myofibrillar and muscle connective protein synthesis rates.
RESULTS
Protein ingestion increased circulating plasma amino acid concentrations ( P < 0.05). The postprandial rise in plasma leucine and essential amino acid concentrations was greater in WHEY compared with COLL, whereas plasma glycine and proline concentrations increased more in COLL compared with WHEY ( P < 0.05). Myofibrillar protein synthesis rates averaged 0.041 ± 0.010, 0.036 ± 0.010, and 0.032 ± 0.007%·h -1 in WHEY, COLL and PLA, respectively, with only WHEY resulting in higher rates when compared with PLA ( P < 0.05). Muscle connective protein synthesis rates averaged 0.072 ± 0.019, 0.068 ± 0.017, and 0.058 ± 0.018%·h -1 in WHEY, COLL, and PLA, respectively, with no significant differences between groups ( P = 0.09).
CONCLUSIONS
Ingestion of whey protein during recovery from exercise increases myofibrillar protein synthesis rates. Neither collagen nor whey protein ingestion further increased muscle connective protein synthesis rates during the early stages of postexercise recovery in both male and female recreational athletes.
Topics: Humans; Male; Female; Young Adult; Adult; Muscle Proteins; Whey Proteins; Collagen; Muscle, Skeletal; Eating; Polyesters; Postprandial Period; Dietary Proteins
PubMed: 37202878
DOI: 10.1249/MSS.0000000000003214 -
The American Journal of Clinical... Feb 2024Protein intake plays an important role in maintaining the health status of older adults. However, few epidemiologic studies examined midlife protein intake in relation...
BACKGROUND
Protein intake plays an important role in maintaining the health status of older adults. However, few epidemiologic studies examined midlife protein intake in relation to healthy aging.
OBJECTIVES
The objective of this study was to evaluate the long-term role of dietary protein intake in healthy aging among female participants in the prospective Nurses' Health Study (NHS) cohort.
METHODS
We included 48,762 NHS participants aged <60 y in 1984. Total protein, animal protein, dairy protein (a subset of animal protein), and plant protein were derived from validated food frequency questionnaires. Healthy aging was defined as being free from 11 major chronic diseases, having good mental health, and not having impairments in either cognitive or physical function, as assessed in the 2014 or 2016 NHS participant questionnaires. We used multivariate logistic regression adjusted for lifestyle, demographics, and health status to estimate the odds ratios (ORs) and 95% confidence intervals for protein intake in relation to healthy aging.
RESULTS
A total of 3721 (7.6%) NHS participants met our healthy aging definition. Protein intake was significantly associated with higher odds of healthy aging. The ORs (95% confidence intervals) per 3%-energy increment with healthy aging were 1.05 (1.01, 1.10) for total protein, 1.07 (1.02, 1.11) for animal protein, 1.14 (1.06, 1.23) for dairy protein, and 1.38 (1.24, 1.54) for plant protein. Plant protein was also associated with higher odds of absence of physical function limitations and good mental status. In substitution analyses, we observed significant positive associations for the isocaloric replacement of animal or dairy protein, carbohydrate, or fat with plant protein (ORs for healthy aging: 1.22-1.58 for 3% energy replacement with plant protein).
CONCLUSIONS
Dietary protein intake, especially plant protein, in midlife, is associated with higher odds of healthy aging and with several domains of positive health status in a large cohort of female nurses.
Topics: Animals; Humans; Aged; Prospective Studies; Healthy Aging; Dietary Proteins; Epidemiologic Studies; Plant Proteins; Nurses; Diet
PubMed: 38309825
DOI: 10.1016/j.ajcnut.2023.11.010 -
Nutrients Sep 2023Proteins and polysaccharides are versatile natural macromolecules that are ubiquitous in nature, and a tailored diet that is fortified with them has been developed to...
Proteins and polysaccharides are versatile natural macromolecules that are ubiquitous in nature, and a tailored diet that is fortified with them has been developed to ameliorate a wide array of diseases [...].
Topics: Food, Fortified; Diet; Nutrition Policy; Dietary Proteins
PubMed: 37836421
DOI: 10.3390/nu15194137