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Innate immune remodeling by short-term intensive fasting.
Qian, J, Fang, Y, Yuan, N, Gao, X, Lv, Y, Zhao, C, Zhang, S, Li, Q, Li, L, Xu, L, et al
Aging cell. 2021;(11):e13507
Abstract
Previous studies have shown that long-term light or moderate fasting such as intermittent fasting can improve health and prolong lifespan. However, in humans short-term intensive fasting, a complete water-only fasting has little been studied. Here, we used multi-omics tools to evaluate the impact of short-term intensive fasting on immune function by comparison of the CD45+ leukocytes from the fasting subjects before and after 72-h fasting. Transcriptomic and proteomic profiling of CD45+ leukocytes revealed extensive expression changes, marked by higher gene upregulation than downregulation after fasting. Functional enrichment of differentially expressed genes and proteins exposed several pathways critical to metabolic and immune cell functions. Specifically, short-term intensive fasting enhanced autophagy levels through upregulation of key members involved in the upstream signals and within the autophagy machinery, whereas apoptosis was reduced by down-turning of apoptotic gene expression, thereby increasing the leukocyte viability. When focusing on specific leukocyte populations, peripheral neutrophils are noticeably increased by short-term intensive fasting. Finally, proteomic analysis of leukocytes showed that short-term intensive fasting not only increased neutrophil degranulation, but also increased cytokine secretion. Our results suggest that short-term intensive fasting boost immune function, in particular innate immune function, at least in part by remodeling leukocytes expression profile.
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2.
Effects of Ramadan fasting on athletes' hematological indices: a systematic review.
Trabelsi, K, Shephard, RJ, Boukhris, O, Ammar, A, El-Abed, K, Khanfir, S, Hakim, A, Bragazzi, NL
La Tunisie medicale. 2019;(10):1104-1113
Abstract
OBJECTIVE To evaluate the effects of Ramadan fasting on hematological data in athletes through a systematic appraisal of the literature. DESIGN Systematic review Data sources: The entire content of two databases, PubMed/MEDLINE and Web of Science Eligibility criteria for selecting studies: Ramadanrelated measurements of any hematological indices in athletes were considered. Both single-group pre-post with and without a control group studies conducted in athletes and published in English language before December 31, 2018 were included. Study appraisal: The methodological quality of the studies identified was assessed using 'QualSyst'. RESULTS Of nine selected articles, eight were of moderate quality and only one was of strong quality. The main problem to date has been a lack of appropriate controls. Compared to before Ramadan, hematocrit and hemoglobin values increased in three studies, decreased in one study and did not change in one study during Ramadan fasting. Another study reported increased hematocrit and a puzzling decrease of hemoglobin during as compared to before Ramadan fasting. In most studies, blood platelet counts and the limited number of immune function used to date remainedunchanged. CONCLUSIONS All reported changes in hematological indices remained within the normal reference range of the laboratory. Therefore, regular training can continue safely during Ramadan fasting from a hematological view point.
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Small-protein Enrichment Assay Enables the Rapid, Unbiased Analysis of Over 100 Low Abundance Factors from Human Plasma.
Harney, DJ, Hutchison, AT, Su, Z, Hatchwell, L, Heilbronn, LK, Hocking, S, James, DE, Larance, M
Molecular & cellular proteomics : MCP. 2019;(9):1899-1915
Abstract
Unbiased and sensitive quantification of low abundance small proteins in human plasma (e.g. hormones, immune factors, metabolic regulators) remains an unmet need. These small protein factors are typically analyzed individually and using antibodies that can lack specificity. Mass spectrometry (MS)-based proteomics has the potential to address these problems, however the analysis of plasma by MS is plagued by the extremely large dynamic range of this body fluid, with protein abundances spanning at least 13 orders of magnitude. Here we describe an enrichment assay (SPEA), that greatly simplifies the plasma dynamic range problem by enriching small-proteins of 2-10 kDa, enabling the rapid, specific and sensitive quantification of >100 small-protein factors in a single untargeted LC-MS/MS acquisition. Applying this method to perform deep-proteome profiling of human plasma we identify C5ORF46 as a previously uncharacterized human plasma protein. We further demonstrate the reproducibility of our workflow for low abundance protein analysis using a stable-isotope labeled protein standard of insulin spiked into human plasma. SPEA provides the ability to study numerous important hormones in a single rapid assay, which we applied to study the intermittent fasting response and observed several unexpected changes including decreased plasma abundance of the iron homeostasis regulator hepcidin.
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Beta cell function in type 1 diabetes determined from clinical and fasting biochemical variables.
Wentworth, JM, Bediaga, NG, Giles, LC, Ehlers, M, Gitelman, SE, Geyer, S, Evans-Molina, C, Harrison, LC, , , ,
Diabetologia. 2019;(1):33-40
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Abstract
AIMS/HYPOTHESIS Beta cell function in type 1 diabetes is commonly assessed as the average plasma C-peptide concentration over 2 h following a mixed-meal test (CPAVE). Monitoring of disease progression and response to disease-modifying therapy would benefit from a simpler, more convenient and less costly measure. Therefore, we determined whether CPAVE could be reliably estimated from routine clinical variables. METHODS Clinical and fasting biochemical data from eight randomised therapy trials involving participants with recently diagnosed type 1 diabetes were used to develop and validate linear models to estimate CPAVE and to test their accuracy in estimating loss of beta cell function and response to immune therapy. RESULTS A model based on disease duration, BMI, insulin dose, HbA1c, fasting plasma C-peptide and fasting plasma glucose most accurately estimated loss of beta cell function (area under the receiver operating characteristic curve [AUROC] 0.89 [95% CI 0.87, 0.92]) and was superior to the commonly used insulin-dose-adjusted HbA1c (IDAA1c) measure (AUROC 0.72 [95% CI 0.68, 0.76]). Model-estimated CPAVE (CPEST) reliably identified treatment effects in randomised trials. CPEST, compared with CPAVE, required only a modest (up to 17%) increase in sample size for equivalent statistical power. CONCLUSIONS/INTERPRETATION CPEST, approximated from six variables at a single time point, accurately identifies loss of beta cell function in type 1 diabetes and is comparable to CPAVE for identifying treatment effects. CPEST could serve as a convenient and economical measure of beta cell function in the clinic and as a primary outcome measure in trials of disease-modifying therapy in type 1 diabetes.
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Time-restricted feeding influences immune responses without compromising muscle performance in older men.
Gasmi, M, Sellami, M, Denham, J, Padulo, J, Kuvacic, G, Selmi, W, Khalifa, R
Nutrition (Burbank, Los Angeles County, Calif.). 2018;:29-37
Abstract
OBJECTIVE This study examined the effect of 12 wk of time-restricted feeding (TRF) on complete blood cell counts, natural killer cells, and muscle performance in 20- and 50-year-old men. METHODS Forty active and healthy participants were randomly divided into young experimental, young control, aged experimental, and aged control group. Experimental groups participated in TRF. Before (P1) and after (P2) TRF, participants performed a maximal exercise test to quantify muscle power. Resting venous blood samples were collected for blood count calculation. RESULTS No changes were identified in muscle power in all groups after TRF (P > 0.05). At P1, red cells, hemoglobin, and hematocrit were significantly higher in young participants compared with elderly participants (P < 0.05). At P2, this age effect was not found in red cells between the young experimental group and the aged experimental group (P > 0.05). At P1, white blood cells and neutrophils were significantly higher in young participants compared with elderly participants (P < 0.05). At P2, only neutrophils decreased significantly (P < 0.05) in experimental groups without significant (P > 0.05) difference among them. Lymphocytes decreased significantly in the aged experimental group at P2 (P < 0.05), whereas NKCD16+ and NKCD56+ decreased significantly in experimental groups at P2 (P < 0.05). TRF had no effect on CD3, CD4+, and CD8+ levels (P > 0.05). CONCLUSION TRF decreases hematocrit, total white blood cells, lymphocytes, and neutrophils in young and older men. TRF may be effective in preventing inflammation by decreasing natural killer cells. As such, TRF could be a lifestyle strategy to reduce systemic low-grade inflammation and age-related chronic diseases linked to immunosenescence, without compromising physical performance.
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Men and women differ in their diurnal expression of monocyte peroxisome proliferator-activated receptor-α in the fed but not in the fasted state.
Wege, N, Schutkowski, A, Boenn, M, Bialek, J, Schlitt, A, Noack, F, Grosse, I, Stangl, GI
FASEB journal : official publication of the Federation of American Societies for Experimental Biology. 2015;(7):2905-11
Abstract
Peroxisome proliferator-activated receptor-α (PPARα) plays a pivotal role in regulating metabolic response to fasting and is an inhibitor of inflammatory pathways in immune cells. It represents a therapeutic target for treatment of several diseases, mainly hyperlipidemia. To shed light on PPARα expression changes in response to fasting, young healthy male and female volunteers were fed or fasted for 24 hours. Monocytes were analyzed every 2 hours to compile both profiles of mRNA and protein expression of PPARα and its interactive partner, the circadian pacemaker brain and muscle aryl hydrocarbon receptor nuclear translocator like-1 (BMAL1). We found that women change their diurnal expression profiles of PPARα and BMAL1 when switching from the fed to the fasted state, whereas men do not. Interestingly, the PPARα and BMAL1 profiles of men and women in the fed state are different, whereas the profiles in the fasted state are virtually identical. The finding of diametrically opposite responses of male and female PPARα expression in the fed state might have practical implication in human medicine as PPARα activators like fibrates are used for the therapy of chronic lymphocytic leukemia, microvascular complications in diabetes, and kidney diseases.
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Fasting and recovery from exercise.
Burke, L
British journal of sports medicine. 2010;(7):502-8
Abstract
Recovery after strenuous exercise involves processes that are dependent on fluid and food intake. Current sports nutrition guidelines provide recommendations for the quantity and timing of consumption of nutrients to optimise recovery issues such as refuelling, rehydration and protein synthesis for repair and adaptation. Recovery of immune and antioxidant systems is important but less well documented. In some cases, there is little effective recovery until nutrients are supplied, while in others, the stimulus for recovery is strongest in the period immediately after exercise. Lack of appropriate nutritional support will reduce adaption to exercise and impair preparation for future bouts. Ramadan represents a special case of intermittent fasting undertaken by many athletes during periods of training as well as important competitive events. The avoidance of fluid and food intake from sunrise to sundown involves prolonged periods without intake of nutrients, inflexibility with the timing of eating and drinking over the day and around an exercise session, and changes to usual dietary choices due to the special foods involved with various rituals. These outcomes will all challenge the athlete's ability to recover optimally between exercise sessions undertaken during the fast or from day to day.