Impact of Postprandial Lipemia and Glycemia on Inflammatory Factors in over 1000 Individuals in the US and UK: Insights from the PREDICT 1 and InterCardio Studies

Abstract Objectives Postprandial glycemia (PPG) and lipemia (PPL) initiate an acute inflammatory response, which may be relevant to future CVD. We characterised the impact of PPL and PPG on inflammatory responses using traditional (IL-6) and emerging (glycoprotein acetyls; GlycA) biomarkers of inflammation in a large scale, tightly controlled study (PREDICT 1; NCT03479866) and an independent validation study (InterCardio; NCT03438084). Methods The PREDICT 1 dietary intervention study of 1102 healthy individuals from the US and UK, assessed the postprandial (0–6 h) metabolic responses to sequential mixed-nutrient meals (50 g fat and 85 g carb at 0 h; 22 g fat and 71 g carb at 4 h). Baseline microbial diversity (16S Shannon diversity) and visceral fat mass (VFM; based on DXA) were also measured. Results were validated in an independent randomised crossover trial (n = 50). For both studies, glucose, triacylglycerol (TG), IL-6 and GlycA were measured at multiple intervals. Results In PREDICT 1, GlycA and IL-6 concentrations increased significantly after meals (by 4.5 and 169%; peak 6 h, respectively) but were not correlated. Peak postprandial TG and glucose concentrations were strongly associated with GlycA (r = 0.832 and r = 0.239, respectively) but not IL-6. Machine learning with cross-validation, revealed that PPL was the strongest predictor of postprandial GlycA. There was evidence of an interaction; individuals with higher microbial diversity and lower VFM had an attenuated inflammatory response. Individuals eliciting an enhanced response (30% rise at 6 h) had higher predicted CVD risk compared to the rest of the cohort. In the InterCardio study, the postprandial inflammatory increase in GlycA was also significantly correlated with PPL and varied within the four different types of fat tested. Conclusions In the first study to investigate postprandial inflammation at scale, we observed that PPL was a stronger determinant of systemic inflammation compared with PPG. The clinically significant and variable postprandial inflammatory response, and its association with lipemia and glycemia, highlights the potential for personalized dietary strategies to lower postprandial metabolic responses to reduce low grade inflammatory related diseases. Funding Sources NIHR, Wellcome Trust, Zoe Global Ltd, BBSRC DRINC.

Download Full-text

C1QTNF6 participates in the pathogenesis of PCOS by affecting the inflammatory response of granulosa cells

Biology of Reproduction ◽

10.1093/biolre/ioab094 ◽

2021 ◽

Author(s):

Sisi Yan ◽

Jinli Ding ◽

Yi Zhang ◽

Jiayu Wang ◽

Sainan Zhang ◽

...

Keyword(s):

Inflammatory Response ◽

Mouse Models ◽

Granulosa Cells ◽

Polycystic Ovary ◽

Serum Levels ◽

Inflammatory Factors ◽

Low Grade ◽

Reactive Protein ◽

Reproductive Endocrine ◽

Factor Α

Abstract Polycystic ovary syndrome (PCOS) is a common reproductive endocrine disease. It has been reported that chronic low-grade inflammation might participate in its pathogenesis. C1q and TNF related 6 (C1QTNF6) is a newly identified adiponectin paralog associated with inflammation. The aim of the present study was to investigate the role of C1QTNF6 in the development of chronic inflammation in PCOS and the underlying molecular mechanism. After analyzing the expression of C1QTNF6 in the serum and granulosa cells (GCs) of PCOS patients and healthy controls, we verified the roles of C1QTNF6 in inflammation through dehydroepiandrosterone-induced PCOS mouse models and cell models of lipopolysaccharide (LPS)-induced inflammation. The results demonstrated that C1QTNF6 expression in the serum and GCs of patients with PCOS was significantly elevated compared with those of the controls, and similar results were observed in the serum and ovary of PCOS mouse models. In PCOS mice and C1QTNF6-overexpressing PCOS mice, serum levels of pro-inflammatory factors including C-reactive protein (CRP), interleukin 6 (IL6) and tumor necrosis factor-α (TNFα) were increased, while the opposite effects were observed when C1QTNF6 was downregulated in PCOS mice. Furthermore, C1QTNF6 overexpression upregulated the levels of TNFα, IL6, and CRP and activated the AKT/NF-κB pathway in LPS-treated KGN cells, whereas C1QTNF6 knockdown and BAY-117082 (an NF-κB inhibitor) treatment resulted in the opposite effects. Taken together, our results indicate that C1QTNF6 is involved in the pathogenesis of PCOS by affecting the inflammatory response via the AKT/NF-κB signaling pathway.

Download Full-text

Comparing the effect of intestinal bacteria from rabbit, pig, and chicken on inflammatory response in cultured rabbit crypt and villus

Canadian Journal of Microbiology ◽

10.1139/cjm-2017-0757 ◽

2019 ◽

Vol 65 (1) ◽

pp. 59-67 ◽

Cited By ~ 1

Author(s):

Hong Xiao Cui ◽

Xiu Rong Xu

Keyword(s):

Inflammatory Response ◽

Inflammatory Responses ◽

Intestinal Bacteria ◽

Inflammatory Factors ◽

Rabbit Ileum ◽

Necrosis Factor Alpha ◽

Heat Treated ◽

Tnf Α ◽

Factor Alpha ◽

Anti Inflammatory

Rabbit is susceptible to intestinal infection, which often results in severe inflammatory response. To investigate whether the special community structure of rabbit intestinal bacteria contributes to this susceptibility, we compared the inflammatory responses of isolated rabbit crypt and villus to heat-treated total bacteria in pig, chicken, and rabbit ileal contents. The dominant phylum in pig and chicken ileum was Firmicutes, while Bacteroidetes was dominant in rabbit ileum. The intestinal bacteria from rabbit induced higher expression of toll-like receptor 4 (TLR4) in rabbit crypt and villus (P < 0.05). TLR2 and TLR3 expression was obviously stimulated by chicken and pig intestinal bacteria (P < 0.05) but not by those of rabbit. The ileal bacteria from those three animals all increased the expression of tumor necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) in crypts and villus (P < 0.05). Chicken and pig ileal bacteria also stimulated the expression of anti-inflammatory factors interferon beta (IFN-β) and IL-10 (P < 0.05), while those of rabbit did not (P > 0.05). In conclusion, a higher abundance of Gram-negative bacteria in rabbit ileum did not lead to more expressive pro-inflammatory cytokines in isolated rabbit crypt and villus, but a higher percentage of Lactobacillus in chicken ileum might result in more expressive anti-inflammatory factors.

Download Full-text

RhTrx-1 ameliorates miroglial neuroinflammation after cerebral ischemic stroke

10.21203/rs.3.rs-18172/v1 ◽

2020 ◽

Author(s):

Yang Jiao ◽

Jianjian Wang ◽

Huixue Zhang ◽

Yuze Cao ◽

Yang Qu ◽

...

Keyword(s):

Ischemic Stroke ◽

Inflammatory Response ◽

Inflammatory Responses ◽

Inflammatory Factors ◽

Experimental Stroke ◽

Inflammasome Activation ◽

Cerebral Ischemic

Abstract Background Microglia are rapidly activated after ischemic stroke and participate in the occurrence of neuroinflammation, which exacerbates the injury of ischemic stroke. Receptor Interacting Serine Threonine Kinase 1 (RIPK1) is thought to be involved in the development of inflammatory responses, but its role in ischemic microglia remains unclear. Here, we applied recombinant human thioredoxin-1 (rhTrx-1), a potential neuroprotective agent, to explore the role of rhTrx-1 in inhibiting RIPK1-mediated neuroinflammatory responses in microglia. Method Middle cerebral artery occlusion (MCAO) and Oxygen and glucose deprivation (OGD) were conducted for in vivo and in vitro experimental stroke models. The expression of RIPK1 in microglia after ischemia was examined. The inflammatory response of microglia was analyzed after treatment with rhTrx-1 and Necrostatin-1 (Nec-1, inhibitors of RIPK1), and the mechanisms were explored. In addition, the effects of rhTrx-1 on neurobehavioral deficits and cerebral infarct volume were examined. Results RIPK1 expression was detected in microglia after ischemia. Molecular docking results showed that rhTrx-1 could directly bind to RIPK1. In vitro experiments found that rhTrx-1 reduced necroptosis, mitochondrial membrane potential damage, Reactive oxygen species (ROS) accumulation and NLR Family, pyrin domain-containing 3 protein (NLRP3) inflammasome activation by inhibiting RIPK-1 expression, and regulated microglial M1/M2 phenotypic changes, thereby reducing the release of inflammatory factors. Consistently, in vivo experiments found that rhTrx-1 treatment attenuated cerebral ischemic injury by inhibiting the inflammatory response. Conclusion Our study demonstrates the role of RIPK1 in microglia-arranged neuroinflammation after cerebral ischemia. Administration of rhTrx-1 provides neuroprotection in ischemic stroke-induced microglial neuroinflammation by inhibiting RIPK1 expression.

Download Full-text

TNFα Mediates Inflammation-Induced Effects on PPARG Splicing in Adipose Tissue and Mesenchymal Precursor Cells

Cells ◽

10.3390/cells11010042 ◽

2021 ◽

Vol 11 (1) ◽

pp. 42

Author(s):

Simona Cataldi ◽

Marianna Aprile ◽

Daniela Melillo ◽

Inès Mucel ◽

Sophie Giorgetti-Peraldi ◽

...

Keyword(s):

Adipose Tissue ◽

Precursor Cells ◽

Dominant Negative ◽

Inflammatory Factors ◽

Diabetic Patients ◽

Low Grade ◽

Mesenchymal Precursor Cells ◽

Inflammatory Macrophages ◽

The Impact

Low-grade chronic inflammation and reduced differentiation capacity are hallmarks of hypertrophic adipose tissue (AT) and key contributors of insulin resistance. We identified PPARGΔ5 as a dominant-negative splicing isoform overexpressed in the AT of obese/diabetic patients able to impair adipocyte differentiation and PPARγ activity in hypertrophic adipocytes. Herein, we investigate the impact of macrophage-secreted pro-inflammatory factors on PPARG splicing, focusing on PPARGΔ5. We report that the epididymal AT of LPS-treated mice displays increased PpargΔ5/cPparg ratio and reduced expression of Pparg-regulated genes. Interestingly, pro-inflammatory factors secreted from murine and human pro-inflammatory macrophages enhance the PPARGΔ5/cPPARG ratio in exposed adipogenic precursors. TNFα is identified herein as factor able to alter PPARG splicing—increasing PPARGΔ5/cPPARG ratio—through PI3K/Akt signaling and SRp40 splicing factor. In line with in vitro data, TNFA expression is higher in the SAT of obese (vs. lean) patients and positively correlates with PPARGΔ5 levels. In conclusion, our results indicate that inflammatory factors secreted by metabolically-activated macrophages are potent stimuli that modulate the expression and splicing of PPARG. The resulting imbalance between canonical and dominant negative isoforms may crucially contribute to impair PPARγ activity in hypertrophic AT, exacerbating the defective adipogenic capacity of precursor cells.

Download Full-text

Physical exercise as a human model of limited inflammatory response

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y98-040 ◽

1998 ◽

Vol 76 (5) ◽

pp. 589-597 ◽

Cited By ~ 53

Author(s):

Pang N Shek ◽

Roy J Shephard

Keyword(s):

Physical Exercise ◽

Inflammatory Response ◽

Inflammatory Responses ◽

Tissue Injury ◽

Active Phase ◽

Human Model ◽

Inflammatory Factors ◽

Trauma Patients ◽

Inflammatory Reactions ◽

Underlying Mechanisms

An inflammatory response represents a fundamental series of humoral and cellular reaction cascades in response to infection, tissue injury, and related insults. An excessive response is commonly seen under the pathological conditions of trauma, sepsis, and burns. It is becoming increasingly evident that most, if not all, of the distinguishing features of a classical inflammatory response are detectable in an exercising individual, namely mobilization and activation of granulocytes, lymphocytes, and monocytes; release of inflammatory factors and soluble mediators; involvement of active phase reactants; and activation of the complement and other reactive humoral cascade systems. While the manifestation of many exercise-induced immune and related changes has been reported and confirmed repeatedly, the underlying mechanisms triggering and modulating the elicited immune responses are, at best, poorly understood. Unlike the exaggerated and sometimes uncontrollable inflammatory response in septic and trauma patients resulting in morbidity and mortality, strenuous and severe exercise normally elicits an inflammatory response of a subclinical nature to facilitate the repairing process for site-specific tissue damage. Regardless of the inciting event, for example trauma, infection, or exercise, and given an appropriate triggering signal, a remarkably similar sequence of inflammatory reactions can be reproduced in the affected host. Therefore, physical exercise and training represent an acceptable and good model for the study of limited inflammatory responses in humans.Key words: trauma, infection, exercise, inflammatory response, cytokines.

Download Full-text

Probiotic yogurt and acidified milk similarly reduce postprandial inflammation and both alter the gut microbiota of healthy, young men

British Journal Of Nutrition ◽

10.1017/s0007114517000885 ◽

2017 ◽

Vol 117 (9) ◽

pp. 1312-1322 ◽

Cited By ~ 38

Author(s):

Kathryn J. Burton ◽

Marta Rosikiewicz ◽

Grégory Pimentel ◽

Ueli Bütikofer ◽

Ueli von Ah ◽

...

Keyword(s):

Inflammatory Response ◽

Gut Microbiota ◽

Young Men ◽

Milk Intake ◽

Lactobacillus Delbrueckii ◽

Low Grade ◽

Probiotic Yogurt ◽

Postprandial Inflammation ◽

The Impact ◽

Low Grade Inflammation

AbstractProbiotic yogurt and milk supplemented with probiotics have been investigated for their role in ‘low-grade’ inflammation but evidence for their efficacy is inconclusive. This study explores the impact of probiotic yogurt on metabolic and inflammatory biomarkers, with a parallel study of gut microbiota dynamics. The randomised cross-over study was conducted in fourteen healthy, young men to test probiotic yogurt compared with milk acidified with 2 % d-(+)-glucono-δ-lactone during a 2-week intervention (400 g/d). Fasting assessments, a high-fat meal test (HFM) and microbiota analyses were used to assess the intervention effects. Baseline assessments for the HFM were carried out after a run-in during which normal milk was provided. No significant differences in the inflammatory response to the HFM were observed after probiotic yogurt compared with acidified milk intake; however, both products were associated with significant reductions in the inflammatory response to the HFM compared with the baseline tests (assessed by IL6, TNFα and chemokine ligand 5) (P<0·001). These observations were accompanied by significant changes in microbiota taxa, including decreased abundance of Bilophila wadsworthia after acidified milk (log 2-fold-change (FC)=–1·5, Padj=0·05) and probiotic yogurt intake (FC=–1·3, Padj=0·03), increased abundance of Bifidobacterium species after acidified milk intake (FC=1·4, Padj=0·04) and detection of Lactobacillus delbrueckii spp. bulgaricus (FC=7·0, Padj<0·01) and Streptococcus salivarius spp. thermophilus (FC=6·0, Padj<0·01) after probiotic yogurt intake. Probiotic yogurt and acidified milk similarly reduce postprandial inflammation that is associated with a HFM while inducing distinct changes in the gut microbiota of healthy men. These observations could be relevant for dietary treatments that target ‘low-grade’ inflammation.

Download Full-text

Plant-Based Nutritional Supplementation Attenuates LPS-Induced Low-Grade Systemic Activation

International Journal of Molecular Sciences ◽

10.3390/ijms22020573 ◽

2021 ◽

Vol 22 (2) ◽

pp. 573

Author(s):

Jin Yu ◽

Hong Zhu ◽

Saeid Taheri ◽

William Mondy ◽

Stephen Perry ◽

...

Keyword(s):

Performance Enhancement ◽

Inflammatory Responses ◽

Inflammatory Diseases ◽

Nutritional Supplementation ◽

Mitochondrial Activity ◽

Low Grade ◽

Loading Test ◽

Insulin Tolerance ◽

Neurological Alterations ◽

The Impact

Plant-based nutritional supplementation has been shown to attenuate and reduce mortality in the processes of both acute and chronic disorders, including diabetes, obesity, cardiovascular disease, cancer, inflammatory diseases, and neurological and neurodegenerative disorders. Low-level systemic inflammation is an important contributor to these afflictions and diets enriched in phytochemicals can slow the progression. The goal of this study was to determine the impact of lipopolysaccharide (LPS)-induced inflammation on changes in glucose and insulin tolerance, performance enhancement, levels of urinary neopterin and concentrations of neurotransmitters in the striatum in mouse models. Both acute and chronic injections of LPS (2 mg/kg or 0.33 mg/kg/day, respectively) reduced glucose and insulin tolerance and elevated neopterin levels, which are indicative of systemic inflammatory responses. In addition, there were significant decreases in striatal neurotransmitter levels (dopamine and DOPAC), while serotonin (5-HT) levels were essentially unchanged. LPS resulted in impaired execution in the incremental loading test, which was reversed in mice on a supplemental plant-based diet, improving their immune function and maintaining skeletal muscle mitochondrial activity. In conclusion, plant-based nutritional supplementation attenuated the metabolic changes elicited by LPS injections, causing systemic inflammatory activity that contributed to both systemic and neurological alterations.

Download Full-text

ATPase Inhibitory Factor 1 Is Critical for Regulating Sevoflurane-Induced Microglial Inflammatory Responses and Caspase-3 Activation

Frontiers in Cellular Neuroscience ◽

10.3389/fncel.2021.770666 ◽

2021 ◽

Vol 15 ◽

Author(s):

Yaru Xu ◽

Ge Gao ◽

Xiaoru Sun ◽

Qidong Liu ◽

Cheng Li

Keyword(s):

Inflammatory Response ◽

Caspase 3 ◽

Inflammatory Responses ◽

Animal Experiments ◽

Atp Synthesis ◽

Inhibitory Factor ◽

Inflammatory Factors ◽

General Anesthetics ◽

General Anesthetic ◽

Inhibitory Factor 1

Postoperative delirium (POD) is one of the most important complications after surgery with general anesthesia, for which the neurotoxicity of general anesthetics is a high-risk factor. However, the mechanism remains largely unknown, which also hinders the effective treatment of POD. Here, we confirmed that a clinical concentration of the general anesthetic sevoflurane increased the expression of inflammatory factors and activated the caspase-3 by upregulating ATPase inhibitory factor 1 (ATPIF1) expression in microglia. Upregulation of ATPIF1 decreased the synthesis of ATP which is an important signaling molecule secreted by microglia. Extracellular supplementation with ATP attenuated the microglial inflammatory response and caspase-3 activation caused by sevoflurane or overexpression of ATPIF1. Additionally, the microglial inflammatory response further upregulated ATPIF1 expression, resulting in a positive feedback loop. Animal experiments further indicated that intraperitoneal injection of ATP significantly alleviated sevoflurane anesthesia-induced POD-related anxiety behavior and memory damage in mice. This study reveals that ATPIF1, an important protein regulating ATP synthesis, mediates sevoflurane-induced neurotoxicity in microglia. ATP supplementation may be a potential clinical treatment to alleviate sevoflurane-induced POD.

Download Full-text

Mediterranean meal favorably effects postrandial oxidative stress response compared with a western meal in healthy women

International Journal for Vitamin and Nutrition Research ◽

10.1024/0300-9831/a000734 ◽

2021 ◽

Author(s):

Tuğçe Bulmuş Tüccar ◽

Gamze Akbulut

Keyword(s):

Oxidative Stress ◽

Inflammatory Responses ◽

Low Grade ◽

Necrosis Factor Alpha ◽

Total Thiol ◽

Healthy Women ◽

Meal Intake ◽

Tnf Α ◽

Hs Crp ◽

The Impact

Abstract. Oxidative stress and inflammation are underlying factors in the pathogenesis of chronic diseases. The postprandial state is characterized by low-grade oxidative and inflammatory responses, but the impact of different dietary patterns on these responses is unclear. The objective of this study was to investigate postprandial oxidative and inflammatory responses to Mediterranean diet (MED) and Western diet (WD) meals. In a randomised crossover design, eleven healthy women, aged between 19–45 years with a body mass index of 20.0–24.9 kg/m2, consumed two different isocaloric meals: MED and WD. Blood samples were collected at fasting and 2, 3, 4 h postprandially and analyzed for oxidative [total antioxidant status (TAS), total oxidant status (TOS), total thiol, native thiol, malondialdehyde (MDA)] and inflammatory [high sensitivity C-reactive protein (hs-CRP), interleukin (IL)-6, IL-17, IL-23, tumor necrosis factor alpha (TNF-α) and nuclear factor kappa B (NF-κB)] markers. MED meal intake resulted in increases in TAS (0.05±0.02 mmol/L; p=0.017), total thiol (23.00±7.69 μmol/L; p=0.013) and native thiol (12.82±4.94 μmol/L; p=0.027), while a decrease in MDA (−0.17±0.06 nmol/L; p=0.022) at 2 h. On the other hand, TAS reduced significantly overall (p=0.005) after WD meal intake. There was a significant increase after WD meal intake for IL-6 (1.39±0.49 pg/mL; p=0.017), IL-17 (4.30±1.50 pg/mL; p=0.017), IL-23 (8.38±3.51 pg/mL; p=0.038) at 4 h. However, serum hs-CRP, TNF-α and NF-κB levels were not changed significantly by meal intake. The results indicate that MED meal induces favorable effects on oxidative stress, while WD meal partially increases inflammation in daily life.

Download Full-text

3417 Impact of Protein-Energy Malnutrition on Outcomes of Heart Failure Hospitalizations

Journal of Clinical and Translational Science ◽

10.1017/cts.2019.279 ◽

2019 ◽

Vol 3 (s1) ◽

pp. 123-123

Author(s):

Adeyinka Charles Adejumo ◽

Olumuyiwa Ogundipe

Keyword(s):

Heart Failure ◽

Clinical Outcomes ◽

Protein Energy Malnutrition ◽

Low Grade ◽

Protein Energy ◽

The Us ◽

Study Population ◽

Comorbidity Index ◽

The Impact ◽

Low Grade Inflammation

OBJECTIVES/SPECIFIC AIMS: Chronically elevated cytokines from un-abating low-grade inflammation in heart failure (HF) results in Protein-Energy Malnutrition (PEM). However, the impact of PEM on clinical outcomes of admissions for HF exacerbations has not been evaluated in a national data. METHODS/STUDY POPULATION: From the 2012-2014 Nationwide Inpatient Sample (NIS) patient’s discharge records for primary HF admissions, we identified patients with concomitant PEM, and their demographic and comorbid factors. We propensity-matched PEM cohorts (32,771) to no-PEM controls (1:1) using a greedy algorithm-based methodology and estimated the effect of different clinical outcomes (SAS 9.4). RESULTS/ANTICIPATED RESULTS: There were 32,771 (~163,885) cases of PEM among the 541,679 (~2,708,395) primary admissions for HF between 2012 and 2014 in the US. PEM cases were older (PEM:76 vs. no-PEM:72 years), Whites (70.75% vs. 67.30%), and had higher comorbid burden, with Deyo-comorbidity index >3 (31.61% vs. 26.30%). However, PEM cases had lower rates of obesity, hyperlipidemia and diabetes. After propensity-matching, PEM was associated with higher mortality (AOR:2.48[2.31-2.66]), cardiogenic shock (3.11[2.79-3.46]), cardiac arrest (2.30[1.96-2.70]), acute kidney failure (1.49[1.44-1.54]), acute respiratory failure (1.57[1.51-1.64]), mechanical ventilation (2.72[2.50-2.97]). PEM also resulted in higher non-routine discharges (2.24[2.17-2.31]), hospital cost ($80,534[78,496-82,625] vs. $43,226[42,376-44,093]) and longer duration of admission (8.61[8.49-8.74] vs. 5.28[5.23-5.34] days). DISCUSSION/SIGNIFICANCE OF IMPACT: In the US, PEM is a common comorbidity among hospitalized HF subjects, and results in devastating health outcomes. Early identification and prevention of PEM in heart failure subjects during clinic visits and prompt treatment of PEM both in the clinic and during hospitalization are essential to decrease the excess burden of PEM.

Download Full-text