Mechanistic studies further showed that such metabolic inflammation is related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect under prolonged nutritional excess
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Endogenous Levels of Circulating Androgens and Risk of Crohn's Disease and Ulcerative C... - 0 views
www.ncbi.nlm.nih.gov/...25844961
Testosterone hormone hormones IBD Crohn's disease ulcerative colitis women disease
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Inflammatory cause of metabolic syndrome via brain stress and NF-κB - 0 views
www.ncbi.nlm.nih.gov/...PMC3314172
metabolic syndrome TLR cytokines hypothalamus brain neurology metabolic syndrome NF-kappaB DIO diet induced obesity over nutrition nutrition inflammation
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intracellular stress-inflammation process for metabolic syndrome has been established in the central nervous system (CNS) and particularly in the hypothalamus
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the CNS and the comprised hypothalamus are known to govern various metabolic activities of the body including appetite control, energy expenditure, carbohydrate and lipid metabolism, and blood pressure homeostasis
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Reactive oxygen species (ROS) refer to a class of radical or non-radical oxygen-containing molecules that have high oxidative reactivity with lipids, proteins, and nucleic acids
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a large measure of intracellular ROS comes from the leakage of mitochondrial electron transport chain (ETC)
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Another major source of intracellular ROS is the intentional generation of superoxides by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
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there are other ROS-producing enzymes such as cyclooxygenases, lipoxygenases, xanthine oxidase, and cytochrome p450 enzymes, which are involved with specific metabolic processes
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To counteract the toxic effects of molecular oxidation by ROS, cells are equipped with a battery of antioxidant enzymes such as superoxide dismutases, catalase, peroxiredoxins, sulfiredoxin, and aldehyde dehydrogenases
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intracellular oxidative stress has been indicated to contribute to metabolic syndrome and related diseases, including T2D [72; 73], CVDs [74-76], neurodegenerative diseases [69; 77-80], and cancers
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intracellular oxidative stress is highly associated with the development of neurodegenerative diseases [69] and brain aging
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mitochondrial dysfunction in hypothalamic proopiomelanocortin (POMC) neurons causes central glucose sensing impairment
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Endoplasmic reticulum (ER) is the cellular organelle responsible for protein synthesis, maturation, and trafficking to secretory pathways
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ER stress has been associated to obesity, insulin resistance, T2D, CVDs, cancers, and neurodegenerative diseases
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under environmental stress such as nutrient deprivation or hypoxia, autophagy is strongly induced to breakdown macromolecules into reusable amino acids and fatty acids for survival
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intact autophagy function is required for the hypothalamus to properly control metabolic and energy homeostasis, while hypothalamic autophagy defect leads to the development of metabolic syndrome such as obesity and insulin resistance
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prolonged oxidative stress or ER stress has been shown to impair autophagy function in disease milieu of cancer or aging
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TLRs are an important class of membrane-bound pattern recognition receptors in classical innate immune defense
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overnutrition constitutes an environmental stimulus that can activate TLR pathways to mediate the development of metabolic syndrome related disorders such as obesity, insulin resistance, T2D, and atherosclerotic CVDs
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Isoforms TLR1, 2, 4, and 6 may be particularly pertinent to pathogenic signaling induced by lipid overnutrition
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hypothalamic TLR4 and downstream inflammatory signaling are activated in response to central lipid excess via direct intra-brain lipid administration or HFD-feeding
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overnutrition-induced metabolic derangements such as central leptin resistance, systemic insulin resistance, and weight gain
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these evidences based on brain TLR signaling further support the notion that CNS is the primary site for overnutrition to cause the development of metabolic syndrome.
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circulating cytokines can limitedly travel to the hypothalamus through the leaky blood-brain barrier around the mediobasal hypothalamus to activate hypothalamic cytokine receptors
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significant evidences have been recently documented demonstrating the role of cytokine receptor pathways in the development of metabolic syndrome components
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entral administration of TNF-α at low doses faithfully replicated the effects of central metabolic inflammation in enhancing eating, decreasing energy expenditure [158;159], and causing obesity-related hypertension
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Resistin, an adipocyte-derived proinflammatory cytokine, has been found to promote hepatic insulin resistance through its central actions
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both TLR pathways and cytokine receptor pathways are involved in central inflammatory mechanism of metabolic syndrome and related diseases.
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In quiescent state, NF-κB resides in the cytoplasm in an inactive form due to inhibitory binding by IκBα protein
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IKKβ activation via receptor-mediated pathway, leading to IκBα phosphorylation and degradation and subsequent release of NF-κB activity
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Research in the past decade has found that activation of IKKβ/NF-κB proinflammatory pathway in metabolic tissues is a prominent feature of various metabolic disorders related to overnutrition
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it happens in metabolic tissues, it is mainly associated with overnutrition-induced metabolic derangements, and most importantly, it is relatively low-grade and chronic
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this paradigm of IKKβ/NF-κB-mediated metabolic inflammation has been identified in the CNS – particularly the comprised hypothalamus, which primarily accounts for to the development of overnutrition-induced metabolic syndrome and related disorders such as obesity, insulin resistance, T2D, and obesity-related hypertension
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evidences have pointed to intracellular oxidative stress and mitochondrial dysfunction as upstream events that mediate hypothalamic NF-κB activation in a receptor-independent manner under overnutrition
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In the context of metabolic syndrome, oxidative stress-related NF-κB activation in metabolic tissues or vascular systems has been implicated in a broad range of metabolic syndrome-related diseases, such as diabetes, atherosclerosis, cardiac infarct, stroke, cancer, and aging
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intracellular oxidative stress seems to be a likely pathogenic link that bridges overnutrition with NF-κB activation leading to central metabolic dysregulation
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overnutrition is an environmental inducer for intracellular oxidative stress regardless of tissues involved
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excessive nutrients, when transported into cells, directly increase mitochondrial oxidative workload, which causes increased production of ROS by mitochondrial ETC
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oxidative stress has been shown to activate NF-κB pathway in neurons or glial cells in several types of metabolic syndrome-related neural diseases, such as stroke [185], neurodegenerative diseases [186-188], and brain aging
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central nutrient excess (e.g., glucose or lipids) has been shown to activate NF-κB in the hypothalamus [34-37] to account for overnutrition-induced central metabolic dysregulations
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overnutrition can present the cell with a metabolic overload that exceeds the physiological adaptive range of UPR, resulting in the development of ER stress and systemic metabolic disorders
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chronic ER stress in peripheral metabolic tissues such as adipocytes, liver, muscle, and pancreatic cells is a salient feature of overnutrition-related diseases
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recent literature supports a model that brain ER stress and NF-κB activation reciprocally promote each other in the development of central metabolic dysregulations
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when intracellular stresses remain unresolved, prolonged autophagy upregulation progresses into autophagy defect
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autophagy defect can induce NF-κB-mediated inflammation in association with the development of cancer or inflammatory diseases (e.g., Crohn's disease)
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The connection between autophagy defect and proinflammatory activation of NF-κB pathway can also be inferred in metabolic syndrome, since both autophagy defect [126-133;200] and NF-κB activation [20-33] are implicated in the development of overnutrition-related metabolic diseases
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Both TLR pathway and cytokine receptor pathways are closely related to IKKβ/NF-κB signaling in the central pathogenesis of metabolic syndrome
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Overnutrition, especially in the form of HFD feeding, was shown to activate TLR4 signaling and downstream IKKβ/NF-κB pathway
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TLR4 activation leads to MyD88-dependent NF-κB activation in early phase and MyD88-indepdnent MAPK/JNK pathway in late phase
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these studies point to NF-κB as an immediate signaling effector for TLR4 activation in central inflammatory response
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TLR4 activation has been shown to induce intracellular ER stress to indirectly cause metabolic inflammation in the hypothalamus
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central TLR4-NF-κB pathway may represent one of the early receptor-mediated events in overnutrition-induced central inflammation.
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cytokines and their receptors are both upstream activating components and downstream transcriptional targets of NF-κB activation
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central administration of TNF-α at low dose can mimic the effect of obesity-related inflammatory milieu to activate IKKβ/NF-κB proinflammatory pathways, furthering the development of overeating, energy expenditure decrease, and weight gain
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the physiological effects of IKKβ/NF-κB activation seem to be cell type-dependent, i.e., IKKβ/NF-κB activation in hypothalamic agouti-related protein (AGRP) neurons primarily leads to the development of energy imbalance and obesity [34]; while in hypothalamic POMC neurons, it primarily results in the development of hypertension and glucose intolerance
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Low S-adenosylmethionine concentrations fo... [Clin Chem Lab Med. 2004] - PubMed - NCBI - 0 views
www.ncbi.nlm.nih.gov/...15259382
SAMe IBD Crohn's disease Ulcerative Colitis methylation methyl donor
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Candida albicans Is an Immunogen for Anti-Saccharomyces cerevisiae Antibody Markers of ... - 0 views
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Calprotectin is a stronger predictive marker of relapse in ulcerative colitis than in C... - 0 views
gut.bmj.com/...364.abstract
Calprotectin IBD inflammatory bowel disease inflammation GI gut ulcerative colitis
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Differentiation between Celiac Disease, Nonceliac Gluten Sensitivity, and Their Overlap... - 0 views
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A human gut microbial gene catalogue established by metagenomic sequencing : Article : ... - 0 views
www.nature.com/...nature08821.html
microbiome health disease ulcerative colitis crohn's gut GI system
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saccharomyces cerevisiae and ulcerative colitis - Google Scholar - 0 views
scholar.google.com/scholar
saccharomyces cerevisiae IBD ulcerative colitis Crohn's disease inflammation disease
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Endocannabinoid System as a Promising Therapeutic Target in Inflammatory Bowel Disease ... - 0 views
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The role of short-chain fatty acids in the interplay between diet, gut microbiota, and ... - 0 views
www.ncbi.nlm.nih.gov/...PMC3735932
SCFA gut gut health diet nutrition metabolism gut flora gut microbiota
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Acetate, propionate, and butyrate are present in an approximate molar ratio of 60:20:20 in the colon and stool
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SCFAs might play a key role in the prevention and treatment of the metabolic syndrome, bowel disorders, and certain types of cancer
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SCFA administration positively influenced the treatment of ulcerative colitis, Crohn's disease, and antibiotic-associated diarrhea
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Gut bacteria in the cecum and large intestine produce SCFAs mainly from nondigestible carbohydrates that pass the small intestine unaffected
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colonocytes, the first host cells that take up SCFAs and which depend largely on butyrate for their energy supply
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the microbiota act as a metabolic organ that can break down otherwise indigestible food components, degrade potentially toxic food compounds like oxalate, and synthesize certain vitamins and amino acids
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The general idea is that colonocytes prefer butyrate to acetate and propionate, and oxidize it to ketone bodies and CO2
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Exogenous acetate formed by colonic bacterial fermentation enters the blood compartment and is mixed with endogenous acetate released by tissues and organs (103, 104). Up to 70% of the acetate is taken up by the liver (105), where it is not only used as an energy source, but is also used as a substrate for the synthesis of cholesterol and long-chain fatty acids and as a cosubstrate for glutamine and glutamate synthesis
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SCFAs regulate the balance between fatty acid synthesis, fatty acid oxidation, and lipolysis in the body.
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obese animals in this study showed a 50% reduction in relative abundance of the Bacteroidetes (i.e., acetate and propionate producers), whereas the Firmicutes (i.e., butyrate producers) were proportionally increased compared with the lean counterparts.
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In humans the distinct relation between the Firmicutes:Bacteroidetes ratio and obesity is less clear.
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Limited effects of dietary curcumin on Th-1 driven colitis in IL-10 deficient mice sugg... - 0 views
www.ncbi.nlm.nih.gov/...PMC2584828
curcumin IL-10 NF-kappaB inflammation IBD ulcerative colitis Crohn's disease
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