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Dietary Regulation of Immunity.
Lee, AH, Dixit, VD
Immunity. 2020;(3):510-523
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Abstract
Integrated immunometabolic responses link dietary intake, energy utilization, and storage to immune regulation of tissue function and is therefore essential for the maintenance and restoration of homeostasis. Adipose-resident leukocytes have non-traditional immunological functions that regulate organismal metabolism by controlling insulin action, lipolysis, and mitochondrial respiration to control the usage of substrates for production of heat versus ATP. Energetically expensive vital functions such as immunological responses might have thus evolved to respond accordingly to dietary surplus and deficit of macronutrient intake. Here, we review the interaction of dietary intake of macronutrients and their metabolism with the immune system. We discuss immunometabolic checkpoints that promote healthspan and highlight how dietary fate and regulation of glucose, fat, and protein metabolism might affect immunity.
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Competition for nutrients and its role in controlling immune responses.
Kedia-Mehta, N, Finlay, DK
Nature communications. 2019;(1):2123
Abstract
Changes in cellular metabolism are associated with the activation of diverse immune subsets. These changes are fuelled by nutrients including glucose, amino acids and fatty acids, and are closely linked to immune cell fate and function. An emerging concept is that nutrients are not equally available to all immune cells, suggesting that the regulation of nutrient utility through competitive uptake and use is important for controlling immune responses. This review considers immune microenvironments where nutrients become limiting, the signalling alterations caused by insufficient nutrients, and the importance of nutrient availability in the regulation of immune responses.
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Immunomodulatory and Metabolic Changes after Gnetin-C Supplementation in Humans.
Nakagami, Y, Suzuki, S, Espinoza, JL, Vu Quang, L, Enomoto, M, Takasugi, S, Nakamura, A, Nakayama, T, Tani, H, Hanamura, I, et al
Nutrients. 2019;(6)
Abstract
Gnetin-C is a naturally occurring stilbene derived from the seeds of Gnetum gnemon L., an edible plant native to Southeast Asia that is called melinjo. Although the biological properties and safety of G. gnemon extract, which contains nearly 3% Gnetin-C, have been confirmed in various human studies, whether or not pure Gnetin-C is safe for humans is unclear at present. We conducted a randomized, double-blind, placebo-controlled trial. Healthy subjects were randomly divided into two groups. The interventional group (n = 6) was given Gnetin-C, and the control group (n = 6) was provided a placebo, for 14 days. Lipid profiles, biomarkers of oxidative stress and circulating blood cells were assessed before and after the intervention. All subjects completed the study, with no side effects reported across the study duration. Gnetin-C supplementation demonstrated a statistically significant increase in the absolute number of circulating natural killer (NK) cells expressing the activating receptors NKG2D and NKp46. NK cells derived from subjects who received Gnetin-C for two weeks showed higher cytotoxicity against K562 target cells than those before receiving Gnetin-C. In addition, Gnetin-C also resulted in a significant decrease in the absolute neutrophil count in the blood compared with the placebo. Furthermore, Gnetin-C significantly reduced the levels of uric acid, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol, total adiponectin, and high-molecular-weight adiponectin. These data indicate that Gnetin-C has biological effects of enhancing the NK activity on circulating human immune cells. The immunomodulatory effects are consistent with a putative improvement in cancer immunosurveillance via the upregulation of the NKG2D receptor. The study was registered with UMIN-CTR, number 000030364, on 12 December 2017.
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Gene Expression and Cardiometabolic Phenotypes of Vitamin D-Deficient Overweight and Obese Black Children.
Rajakumar, K, Yan, Q, Khalid, AT, Feingold, E, Vallejo, AN, Demirci, FY, Kamboh, MI
Nutrients. 2019;(9)
Abstract
Associations between whole blood transcriptome and clinical phenotypes in vitamin D-deficient overweight and obese children can provide insight into the biological effects of vitamin D and obesity. We determined differentially expressed genes (DEGs) in relation to body mass index (BMI) in vitamin D-deficient black children with a BMI ≥ 85th percentile and ascertained the cardiometabolic phenotypes associated with the DEGs. We examined whole-blood transcriptome gene expression by RNA sequencing and cardiometabolic profiling in 41, 10- to 18-year-old children. We found 296 DEGs in association with BMI after adjusting for age, race, sex, and pubertal status. Cardiometabolic phenotypes associated with the BMI-related DEGs, after adjusting for age, sex, pubertal status, and %total body fat, were (i) flow-mediated dilation (marker of endothelial function), (ii) c-reactive protein (marker of inflammation), and (iii) leptin (adipocytokine). Canonical pathways of relevance for childhood obesity and its phenotypes that were significantly associated with the BMI-related DEGs affected immune cell function/inflammation, vascular health, metabolic function, and cell survival/death; several immune and inflammatory pathways overlapped across the three phenotypes. We have identified transcriptome-based biomarkers associated with BMI in vitamin D-deficient, overweight and obese black children. Modulating effects of vitamin D supplementation on these biomarkers and their related phenotypes need further exploration.
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Insulin resistance - "the good or the bad and ugly".
Szosland, K, Lewinski, A
Neuro endocrinology letters. 2018;(5):355-362
Abstract
Insulin resistance (IR) is a state of decreased sensitivity or responsiveness of target tissues to metabolic actions of circulating insulin. IR can be selective, involving only certain aspects of insulin action, i.e. only its impact on hepatic glucose disposal. Plasma insulin concentration is a continuous variable, dependent upon several physiological stimuli, thus the thresholds used to diagnose IR are arbitrary. Insulin resistance (impaired insulin action) may occur due to derangements on three levels: pre-receptor (antibodies against insulin, defected insulin molecule), receptor (defects of insulin receptor, anti-receptor antibodies) and post-receptor (disregulated intracellular pathways). The aim of the study has been promoting the opinion that IR itself cannot be considered only a harmful phenomenon. Detrimental effect is rather chronic hyperinsulinemia related to IR. IR appears important physiological mechanism responsible for adaptation to various stresses: physical, as well as emotional/physiological. Diurnal, seasonal, age-related, pregnancy-associated, and illness-induced fluctuations in food intake and energy expenditure necessitate homeostatic versatility, including the capacity to vary insulin sensitivity, so as to optimize partitioning between tissues of a variable nutrient supply. IR has positively been selected during evolution for the short-lived energy-consuming activation of the brain or immune system. Physiologic situations that require organisms to reserve priority nutrient access for an emerging metabolic requirement, for example immune system activation or foetal development, promote the decrease of systemic insulin sensitivity, reducing nutrient uptake by non-priority tissues and reserving glucose for priority cells. It has been suggested that IR is a mechanism of antioxidant defence in conditions of nutrient energy excess.
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The impact of protein quantity during energy restriction on genome-wide gene expression in adipose tissue of obese humans.
Van Bussel, IPG, Backx, EMP, De Groot, CPGM, Tieland, M, Müller, M, Afman, LA
International journal of obesity (2005). 2017;(7):1114-1120
Abstract
BACKGROUND Overweight and obesity is a growing health problem worldwide. The most effective strategy to reduce weight is energy restriction (ER). ER has been shown to be beneficial in disease prevention and it reduces chronic inflammation. Recent studies suggest that reducing the protein quantity of a diet contributes to the beneficial effects by ER. The organ most extensively affected during ER is white adipose tissue (WAT). OBJECTIVE The first objective was to assess changes in gene expression between a high-protein diet and a normal protein diet during ER. Second, the total effect of ER on changes in gene expression in WAT was assessed. METHODS In a parallel double-blinded controlled study, overweight older participants adhered to a 25% ER diet, either combined with high-protein intake (HP-ER, 1.7 g kg-1 per day), or with normal protein intake (NP-ER, 0.9 g kg-1 per day) for 12 weeks. From 10 HP-ER participants and 12 NP-ER participants subcutaneous WAT biopsies were collected before and after the diet intervention. Adipose tissue was used to isolate total RNA and to evaluate whole-genome gene expression changes upon a HP-ER and NP-ER diet. RESULTS A different gene expression response between HP-ER and NP-ER was observed for 530 genes. After NP-ER, a downregulation in expression of genes linked to immune cell infiltration, adaptive immune response and inflammasome was found, whereas no such effect was found after HP-ER. HP-ER resulted in upregulation in expression of genes linked to cell cycle, GPCR signalling, olfactory signalling and nitrogen metabolism. Upon 25% ER, gene sets related to energy metabolism and immune response were decreased. CONCLUSIONS Based on gene expression changes, we concluded that consumption of normal protein quantity compared with high-protein quantity during ER has a more beneficial effect on inflammation-related gene expression in WAT.
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Selected In-Season Nutritional Strategies to Enhance Recovery for Team Sport Athletes: A Practical Overview.
Heaton, LE, Davis, JK, Rawson, ES, Nuccio, RP, Witard, OC, Stein, KW, Baar, K, Carter, JM, Baker, LB
Sports medicine (Auckland, N.Z.). 2017;(11):2201-2218
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Abstract
Team sport athletes face a variety of nutritional challenges related to recovery during the competitive season. The purpose of this article is to review nutrition strategies related to muscle regeneration, glycogen restoration, fatigue, physical and immune health, and preparation for subsequent training bouts and competitions. Given the limited opportunities to recover between training bouts and games throughout the competitive season, athletes must be deliberate in their recovery strategy. Foundational components of recovery related to protein, carbohydrates, and fluid have been extensively reviewed and accepted. Micronutrients and supplements that may be efficacious for promoting recovery include vitamin D, omega-3 polyunsaturated fatty acids, creatine, collagen/vitamin C, and antioxidants. Curcumin and bromelain may also provide a recovery benefit during the competitive season but future research is warranted prior to incorporating supplemental dosages into the athlete's diet. Air travel poses nutritional challenges related to nutrient timing and quality. Incorporating strategies to consume efficacious micronutrients and ingredients is necessary to support athlete recovery in season.