Skip to main content

Home/ Dr. Goodyear/ Group items tagged liver metabolism

Rss Feed Group items tagged

Filter: All | Bookmarks | Topics Simple Middle
Nathan Goodyear

Nonalcoholic Fatty Liver Disease - 0 views

diabetes.diabetesjournals.org/...1844.short

nonalcoholic fatty liver disease metabolic syndrome

shared by Nathan Goodyear on 06 Apr 11 - No Cached
  • aracterized by clinical and laboratory data similar to those found in diabetes and obesity. NAF
  • We concluded that NAFLD, in the presence of normoglycemia and normal or moderately increased body weight, is ch
  • aracterized by clinical and laboratory data similar to those found in diabetes and obesity. NAF
  • ...1 more annotation...
  • LD may be considered an additional feature of the metabolic syndrome, with specific hepatic insulin resistance
  • Nathan Goodyear on 06 Apr 11
     
    Fatty Liver is component of Metabolic Syndrome
Nathan Goodyear

Vitamin-Dependent Methionine Metabolism and Alcoholic Liver Disease - 0 views

advances.nutrition.org/...421.full

methionine metabolism Alcoholic liver disease vitamin B12 Folate B6 transmethylation methylation pathway

shared by Nathan Goodyear on 28 Oct 11 - No Cached
  • Nathan Goodyear on 28 Oct 11
     
    nice article discussing disrupted methionine metabolism and development of Alcoholic Liver Disease
Nathan Goodyear

Adrenocortical dysregulation as a major player in insulin resistance and onset of obesity - 0 views

ajpendo.physiology.org/...E1465.long

cortisol insulin resistance metabolic syndrome obesity overweight

shared by Nathan Goodyear on 14 Mar 12 - No Cached
  • acute GC secretion during stress mobilizes peripheral amino acids from muscle as well as fatty acids and glycerol from peripheral fat stores to provide substrates for glucose synthesis by the liver
  • chronically elevated GC levels alter body fat distribution and increase visceral adiposity as well as metabolic abnormalities in a fashion reminiscent of metabolic syndrome
  • This local production may play an important role in the onset of obesity and insulin resistance.
  • ...9 more annotations...
  • In adipocytes, cortisol inhibits lipid mobilization in the presence of insulin, thus leading to triglyceride accumulation and retention.
  • Since the density of GC receptors is higher in intra-abdominal (visceral) fat than in other fat depots, the activity of cortisol leading to accumulation of fat is accentuated in visceral adipose tissue (24, 158), providing a mechanism by which excessive endogenous or exogenous GC lead to abdominal obesity and IR
  • obese patients generally have normal or subnormal plasma cortisol concentrations
  • This may be explained by an increased intratissular/cellular concentration of cortisol in adipose tissues
  • Intracellular GC may be produced from recycling of GC metabolites such as cortisone in adipose tissues
  • Local GC recycling metabolism is mediated by 11β-hydroxysteroid dehydrogenase enzymes (11β-HSD1 and 11β-HSD2
  • Cortisol also increases 11β-HSD1 expression in human adipocytes
  • In humans, elevated 11β-HSD1 expression in visceral adipose tissue is also associated with obesity
  • even if obese patients generally have normal or subnormal plasma cortisol concentrations (131, 158), triglyceride accumulation in visceral adipose tissue may be due, at least in part, to the local production of GC in insulin- and GC-responsive organs such as adipose tissue, liver, and skeletal muscle
  • Nathan Goodyear on 14 Mar 12
     
    another nice article on the dysregulation of cortisol and its role in insulin resistance, metabolic syndrome, and obesity.
Nathan Goodyear

Metabolic endotoxemia: a molecular link between obesity and cardiovascular risk - 0 views

jme.endocrinology-journals.org/...R51.full

metabolic endotoxemia obesity insulin resistance cardiovascular disease LPS inflammation

shared by Nathan Goodyear on 04 Aug 14 - No Cached
  • Weight gain has been associated with a higher gut permeability
  • a high-fat diet promotes LPS absorption
  • higher concentrations of fatty acids impair intestinal barrier integrity
  • ...37 more annotations...
  • The starting point for innate immunity activation is the recognition of conserved structures of bacteria, viruses, and fungal components through pattern-recognition receptors
  • TLRs are PRRs that recognize microbe-associated molecular patterns
  • TLRs are transmembrane proteins containing extracellular domains rich in leucine repeat sequences and a cytosolic domain homologous to the IL1 receptor intracellular domain
  • The major proinflammatory mediators produced by the TLR4 activation in response to endotoxin (LPS) are TNFα, IL1β and IL6, which are also elevated in obese and insulin-resistant patients
  • Obesity, high-fat diet, diabetes, and NAFLD are associated with higher gut permeability leading to metabolic endotoxemia.
  • Probiotics, prebiotics, and antibiotic treatment can reduce LPS absorption
  • LPS promotes hepatic insulin resistance, hypertriglyceridemia, hepatic triglyceride accumulation, and secretion of pro-inflammatory cytokines promoting the progression of fatty liver disease.
  • In the endothelium, LPS induces the expression of pro-inflammatory, chemotactic, and adhesion molecules, which promotes atherosclerosis development and progression.
  • In the adipose tissue, LPS induces adipogenesis, insulin resistance, macrophage infiltration, oxidative stress, and release of pro-inflammatory cytokines and chemokines.
  • the gut microbiota has been recently proposed to be an environmental factor involved in the control of body weight and energy homeostasis by modulating plasma LPS levels
  • dietary fats alone might not be sufficient to cause overweight and obesity, suggesting that a bacterially related factor might be responsible for high-fat diet-induced obesity.
  • This was accompanied in high-fat-fed mice by a change in gut microbiota composition, with reduction in Bifidobacterium and Eubacterium spp.
  • n humans, it was also shown that meals with high-fat and high-carbohydrate content (fast-food style western diet) were able to decrease bifidobacteria levels and increase intestinal permeability and LPS concentrations
  • it was demonstrated that, more than the fat amount, its composition was a critical modulator of ME (Laugerette et al. 2012). Very recently, Mani et al. (2013) demonstrated that LPS concentration was increased by a meal rich in saturated fatty acids (SFA), while decreased after a meal rich in n-3 polyunsaturated fatty acids (n-3 PUFA).
  • this effect seems to be due to the fact that some SFA (e.g., lauric and mystiric acids) are part of the lipid-A component of LPS and also to n-3 PUFA's role on reducing LPS potency when substituting SFA in lipid-A
  • these experimental results suggest a pivotal role of CD14-mediated TLR4 activation in the development of LPS-mediated nutritional changes.
  • This suggests a link between gut microbiota, western diet, and obesity and indicates that gut microbiota manipulation can beneficially affect the host's weight and adiposity.
  • endotoxemia was independently associated with energy intake but not fat intake in a multivariate analysis
  • in vitro that endotoxemia activates pro-inflammatory cytokine/chemokine production via NFκB and MAPK signaling in preadipocytes and decreased peroxisome proliferator-activated receptor γ activity and insulin responsiveness in adipocytes.
  • T2DM patients have mean values of LPS that are 76% higher than healthy controls
  • LPS-induced release of glucagon, GH and cortisol, which inhibit glucose uptake, both peripheral and hepatic
  • LPSs also seem to induce ROS-mediated apoptosis in pancreatic cells
  • Recent evidence has been linking ME with dyslipidemia, increased intrahepatic triglycerides, development, and progression of alcoholic and nonalcoholic fatty liver disease
  • The hepatocytes, rather than hepatic macrophages, are the cells responsible for its clearance, being ultimately excreted in bile
  • All the subclasses of plasma lipoproteins can bind and neutralize the toxic effects of LPS, both in vitro (Eichbaum et al. 1991) and in vivo (Harris et al. 1990), and this phenomenon seems to be dependent on the number of phospholipids in the lipoprotein surface (Levels et al. 2001). LDL seems to be involved in LPS clearance, but this antiatherogenic effect is outweighed by its proatherogenic features
  • LPS produces hypertriglyceridemia by several mechanisms, depending on LPS concentration. In animal models, low-dose LPS increases hepatic lipoprotein (such as VLDL) synthesis, whereas high-dose LPS decreases lipoprotein catabolism
  • When a dose of LPS similar to that observed in ME was infused in humans, a 2.5-fold increase in endothelial lipase was observed, with consequent reduction in total and HDL. This mechanism may explain low HDL levels in ‘ME’ and other inflammatory conditions such as obesity and metabolic syndrome
  • It is known that the high-fat diet and the ‘ME’ increase intrahepatic triglyceride accumulation, thus synergistically contributing to the development and progression of alcoholic and NAFLD, from the initial stages characterized by intrahepatic triglyceride accumulation up to chronic inflammation (nonalcoholic steatohepatitis), fibrosis, and cirrhosis
  • On the other hand, LPS activates Kupffer cells leading to an increased production of ROS and pro-inflammatory cytokines like TNFα
  • high-fat diet mice presented with ME, which positively and significantly correlated with plasminogen activator inhibitor (PAI-1), IL1, TNFα, STAMP2, NADPHox, MCP-1, and F4/80 (a specific marker of mature macrophages) mRNAs
  • prebiotic administration reduces intestinal permeability to LPS in obese mice and is associated with decreased systemic inflammation when compared with controls
  • Cani et al. also found that high-fat diet mice presented with not only ME but also higher levels of inflammatory markers, oxidative stress, and macrophage infiltration markers
  • This suggests that important links between gut microbiota, ME, inflammation, and oxidative stress are implicated in a high-fat diet situation
  • high-fat feeding is associated with adipose tissue macrophage infiltration (F4/80-positive cells) and increased levels of chemokine MCP-1, suggesting a strong link between ME, proinflammatory status, oxidative stress, and, lately, increased CV risk
  • LPS has been shown to promote atherosclerosis
  • markers of systemic inflammation such as circulating bacterial endotoxin were elevated in patients with chronic infections and were strong predictors of increased atherosclerotic risk
  • As a TLR4 ligand, LPS has been suggested to induce atherosclerosis development and progression, via a TLR4-mediated inflammatory state.
  • Nathan Goodyear on 04 Aug 14
     
    Very nice updated review on Metabolic endotoxemia
Nathan Goodyear

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

shared by Nathan Goodyear on 09 Nov 16 - No Cached
  • Acetate, propionate, and butyrate are present in an approximate molar ratio of 60:20:20 in the colon and stool
  • SCFAs might play a key role in the prevention and treatment of the metabolic syndrome, bowel disorders, and certain types of cancer
  • SCFA administration positively influenced the treatment of ulcerative colitis, Crohn's disease, and antibiotic-associated diarrhea
  • ...16 more annotations...
  • Gut bacteria in the cecum and large intestine produce SCFAs mainly from nondigestible carbohydrates that pass the small intestine unaffected
  • plant cell-wall polysaccharides, oligosaccharides, and resistant starches
  • inulin shifted the relative production of SCFAs from acetate to propionate and butyrate
  • age of approximately 3–4 years, when it becomes mature
  • SCFAs affect lipid, glucose, and cholesterol metabolism
  • colonocytes, the first host cells that take up SCFAs and which depend largely on butyrate for their energy supply
  • the microbiota educate the immune system and increase the tolerance to microbial immunodeterminants
  • 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
  • a large part of the SCFAs is used as a source of energy
  • The general idea is that colonocytes prefer butyrate to acetate and propionate, and oxidize it to ketone bodies and CO2
  • 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
  • SCFAs regulate the balance between fatty acid synthesis, fatty acid oxidation, and lipolysis in the body.
  • Fatty acid oxidation is activated by SCFAs, while de novo synthesis and lipolysis are inhibited
  • 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.
  • increase in total fecal SCFA concentrations in obese humans.
  • In humans the distinct relation between the Firmicutes:Bacteroidetes ratio and obesity is less clear.
  • Nathan Goodyear on 09 Nov 16
     
    Great review of the role of SCFA in gut health and body metabolism
Nathan Goodyear

Metabolic Effects of Liothyronine Therapy in Hypothyroidism: A Randomized, Double-Blind... - 0 views

press.endocrine.org/...jc.2011-1329

T4 T3 hypothyroid hypothyroidism thyroid lipids weight loss metabolism cholesterol hormones

shared by Nathan Goodyear on 24 Sep 14 - No Cached
  • tissue euthyroidism is the net result of multiple steps including conversion of the prohormone T4 into its active metabolite T3, which is ultimately responsible for signaling at the end-organ target level
  • The circulating and intracellular pools of T3 of treated hypothyroid patients (i.e. devoid of endogenous TH production) depend entirely on the conversion of exogenous l-T4 into T3
  • TH is the major regulator of basal metabolic rate
  • ...8 more annotations...
  • The substitution of l-T3 for l-T4 caused a significant weight loss
  • The substitution of l-T3 for l-T4 caused a significant reduction in lipid parameters
  • Despite the increase in serum T3, the l-T3 treatment did not cause major changes in cardiovascular or musculoskeletal function, as indicated by the echocardiographic and maximal exercise tolerance tests and DXA studies.
  • The changes in serum lipid metabolism parameters are similar to the effects observed with drugs approved for the treatment of dyslipidemia
  • This differential response appears to be limited to the lipid metabolism and SHBG, whereas no differences in indices of insulin resistance were detected. This is remarkable because hyperthyroid states are associated with an increase in hepatic gluconeogenesis (37), and overt thyrotoxicosis is a known cause of secondary diabetes.
  • TH action is increased in the liver, and the SHBG increase supports this hypothesis
  • Similarly, no significant differences were observed in blood pressure, heart rate, or endothelial vascular function
  • In conclusion, the results of this pharmacology, proof-of-concept study indicate that replacement therapy of hypothyroidism with l-T3, compared with l-T4 causes weight loss and favorable changes in the lipid profile without appreciable side effects
  • Nathan Goodyear on 24 Sep 14
     
    Crossover study finds T3 versus T4 results in more weight loss, improved lipid management and increased SHBG without any adverse cardiovascular effects.   The T3 was dosed 3 x daily due to its short half life compared to T4.
Nathan Goodyear

Testosterone and metabolic syndrome Cunningham GR - Asian J Androl - 0 views

www.ajandrology.com/article.asp

Testosterone metabolic syndrome MetS TT total Testosterone SHBG men male hormone hormones Estradiol insulin resistance

shared by Nathan Goodyear on 02 Mar 15 - No Cached
  • The relationship of low testosterone to MetS often is considered to be bidirectional; however, the relationships probably are not direct
  • Many of the components of the MetS are recognized risk factors for the development of cardiovascular disease (CVD)
  • Multiple cross-sectional studies have found low TT and low sex hormone binding globulin (SHBG) levels in Caucasian and African-American men with the MetS, irrespective of age
  • ...20 more annotations...
  • Low TT and SHBG levels also are prevalent in Chinese [7],[8] and Korean [9] men with the MetS
  • Normally 40%-50% of TT is bound to SHBG, so reducing SHBG levels will decrease TT.
  • Hyperinsulinism suppresses SHBG synthesis and secretion by the liver
  • significant increase in SHBG levels occurred after acutely lowering insulin levels in obese men
  • Estradiol levels are increased in men with the MetS, and they are positively correlated with the number of abnormal components of the MetS.
  • Although it is known that estrogen will increase SHBG levels, apparently the hyperinsulinism associated with obesity has a greater effect on SHBG levels
  • Estradiol also can inhibit luteinizing hormone (LH) secretion
  • Inflammatory cytokines are thought to have a direct effect on the pituitary to reduce LH secretion [15] and also a direct effect on Leydig cell secretion of testosterone
  • Low TT Levels have been shown to predict development of the MetS in men with normal BMI
  • Men in the lowest quartiles of serum TT, calculated free testosterone (cFT) and SHBG at baseline had the highest odds ratios for developing the MetS or DM during the 11 years follow-up
  • More recently, investigators conducting population-based studies have reported that only SHBG is associated with future development of the MetS
  • Additional evidence that low TT increases the risk of MetS comes from androgen deprivation treatment of prostate cancer
  • Low TT and low bioavailable testosterone (bT) were each significantly associated with elevated 20 years risk of CVD mortality in an older population in which cause-specific mortality was age, adiposity, and lifestyle-adjusted.
  • combination of low bT and ATP III-defined MetS is associated with increased cardiovascular mortality in men aged 40 years and above
  • in elderly men, testosterone may weakly protect against CVD. Alternatively, low TT may indicate poor general health
  • Muraleedharan and Jones [27] concluded that there is convincing evidence that low T is a biomarker for disease severity and mortality.
  • The evidence that TRT improves insulin sensitivity and glucose control is conflicted
  • It is widely recognized that testosterone treatment can reduce fat mass and increase lean body mass; however, until recently most reports have not been associated with much weight loss
  • Changes in body composition and weight loss are considered potential mechanisms by which testosterone treatment improves insulin sensitivity and glucose control in patients with diabetes. Effects on inflammatory cytokines [38] and changes in oxidative metabolism [39] also have been reported to improve glucose metabolism.
  • Testosterone replacement therapy has been reported to improve some or all of the components of the MetS.
  • Nathan Goodyear on 02 Mar 15
     
    To be read article on Testosterone and Metabolic Syndrome.
Nathan Goodyear

Tissue-Specific Dysregulation of Cortisol Metabolism in Human Obesity - 0 views

jcem.endojournals.org/...1418.short

11-betaHSD cortisone cortisol men obesity overweight fat adipose tissue adiposity

shared by Nathan Goodyear on 13 Mar 12 - No Cached
  • Nathan Goodyear on 13 Mar 12
     
    dysregulated cortisol metabolism plays a role in obesity.  This study looked at obese men.  Decreased liver 11-betaHSD1 activity was found in the liver, with decreased cortisone to cortisol conversion.  Additionally, increase cortisol metabolites were found.  However, there was found to be an increase in 11-betaHSD1 activity in the adipose tissue increasing the cortisone to cortisol conversion indicating an increase in peripheral cortisol production.
Nathan Goodyear

Fructose decreases physical activity and increases body fat without affecting hippocamp... - 0 views

www.nature.com/...srep09589.html

fructose obesity fat diet nutrition activity physical activity

shared by Nathan Goodyear on 03 Aug 15 - No Cached
  • the fructose animals gained significantly more weight than the glucose animals
  • The average liver mass of mice in the fructose treatment group was 20% heavier than for mice in the glucose group
  • The fat pads of mice consuming the fructose diet were 69% heavier than the fat pads of animals consuming the glucose diet
  • ...12 more annotations...
  • there are many studies showing that consumption of fructose in comparison to other monosaccharides results in increased de novo lipogenesis, dyslipidemia, insulin resistance, BW6, 7 and, most recently, impaired cognitive function
  • in the present study, the intake of fructose by mice was more similar to that of typical human consumption in comparison to previous studies
  • prolonged consumption of diets containing fructose (11 weeks) increased BW and body fat deposition
  • studies in humans confirm that fructose, but not glucose (when provided as 25% of energy requirements), in the context of an energy-balanced diet increases de novo lipogenesis and visceral adiposity along with dyslipidemia, decreases insulin sensitivity10, 12 and decreases in fat oxidation
  • we hypothesize that fructose may reduce voluntary energy expenditure in terms of physical activity.
  • significant reduction (~20%) in physical activity in the fructose-fed animals in comparison to glucose
  • a recent study reported that ingestion of fructose (25% energy intake, 10 weeks) in human volunteers also resulted in reduced energy expenditure in relation to a diet with the same glucose dose
  • There is certainly evidence to suggest that, for example, exercise is able to prevent dyslipidemia in healthy subjects fed a weight-maintenance high-fructose diet (30%)54, which strongly suggests a protective role of physical activity in metabolic regulation.
  • the potential negative effects of fructose in brain and cognitive function have been investigated, with a series of studies showing cognitive deficits in spatial memory and learning in adolescent and adult animals following access to a high fructose diet
  • access to both fructose and sucrose, but not glucose, results in a 40% reduction in hippocampal neurogenesis
  • Collectively these studies seem to suggest that fructose consumption can have a considerable impact on hippocampal function and learning, which is in direct contrast with what we observed.
  • the impact of fructose is apparent only in BW, liver mass and body fat, but not in cognitive measures or rates of neurogenesis
  • Nathan Goodyear on 03 Aug 15
     
    animal study finds that fructose increased liver mass, abdominal fat and decreased physical activity when compared to glucose.  The study groups were iso caloric, but one group was fed 18% fructose and the other 18% glucose.
Nathan Goodyear

Vitamin D metabolism and chronic liver disease. - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...6329069

calcium vitamin D liver disease cirrhosis

shared by Nathan Goodyear on 05 Oct 15 - No Cached
  • Nathan Goodyear on 05 Oct 15
     
    only abstract available. Liver disease results in dysfunctional vitamin D metabolism and thus calcium deficiencies.
Nathan Goodyear

Epidemiology of non-alcoholic fatty liver disease. [Dig Dis. 2010] - PubMed result - 0 views

www.ncbi.nlm.nih.gov/...20460905

non-alcoholic liver fatty disease NAFLD obesity metabolic syndrome overweight

shared by Nathan Goodyear on 19 Aug 11 - No Cached
  • Nathan Goodyear on 19 Aug 11
     
    non-alcoholic fatty liver disease the result of Metabolic syndrome.  New epidemic associated with obesity. Scary statistics about the children of America.
Nathan Goodyear

Branched-chain amino acids and muscle ammoni... [Metab Brain Dis. 2013] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23315357

NH3 muscle brain urea cycle metabolism BCAA branched chain amino acids liver cirrhosis disease

shared by Nathan Goodyear on 10 Feb 14 - No Cached
  • BCAA metabolism may improve muscle net ammonia removal by supplying carbon skeletons for formation of alfa-ketoglutarate that combines with two ammonia molecules to become glutamine
  • Nathan Goodyear on 10 Feb 14
     
    Muscle becomes the primary mode of NH3 metabolism in liver cirrhosis.  The authors here propose that it is via an increase in muscle mass rather than specifically lowering NH3.  In fact, there is an early increase in NH3 production.
Nathan Goodyear

Glucocorticoids and 11beta-hydroxysteroid... [Minerva Endocrinol. 2007] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17912154

cortisol 11-betaHSD1 obesity metabolic syndrome

shared by Nathan Goodyear on 14 Mar 12 - No Cached
  • Nathan Goodyear on 14 Mar 12
     
    Dysregulation of 11-betaHSD1 plays significant role in metabolic syndrome.  Decreased 11-betaHSD activity is found in the liver and increased 11-betaHSD1  is found in peripheral fat.  Take home: 11-betaHSD1 activity and cortisol metabolism differs in different tissue
Nathan Goodyear

Metabolic Syndrome ePoster - 0 views

www.nature.com/...eposter_full.html

metabolic syndrome metabolic endotoxemia inflammation macrophage adipose tissue obesity fat muscle pancreas liver brain metabolic syndrome

shared by Nathan Goodyear on 15 Jan 13 - No Cached
  • Nathan Goodyear on 15 Jan 13
     
    Great pictorials of the biochemistry of metabolic syndrome.
Nathan Goodyear

High-Dose Vitamin C for Cancer Therapy - PMC - 0 views

www.ncbi.nlm.nih.gov/...PMC9231292

vitamin C cancer

shared by Nathan Goodyear on 27 Jul 22 - No Cached
  • diabetes [8], atherosclerosis [9], the common cold [10], cataracts [11], glaucoma [12], macular degeneration [13], stroke [14], heart disease [15], COVID-19 [16], and cancer.
  • 1–5% of the Vit-C inside the human cells
  • interaction between Fe(II) and H2O2 produces OH− through the Fenton reaction
  • ...35 more annotations...
  • metabolic activity, oxygen transport, and DNA synthesis
  • Iron is found in the human body in the form of haemoglobin in red blood cells and growing erythroid cells.
  • macrophages contain considerable quantities of iron
  • iron is taken up by the majority of cells in the form of a transferrin (Tf)-Fe(III) complex that binds to the cell surface receptor transferrin receptor 1 (TfR1)
  • excess iron is retained in the liver cells
  • the endosomal six transmembrane epithelial antigen of the prostate 3 (STEAP3) reduces Fe(III) (ferric ion) to Fe(II) (ferrous ion), which is subsequently transferred across the endosomal membrane by divalent metal transporter 1 (DMT1)
  • labile iron pool (LIP)
  • LIP is toxic to the cells owing to the production of massive amounts of ROS.
  • DHA is quickly converted to Vit-C within the cell, by interacting with reduced glutathione (GSH) [45,46,47]. NADPH then recycles the oxidized glutathione (glutathione disulfide (GSSG)) and converts it back into GSH
  • Fe(II) catalyzes the formation of OH• and OH− during the interaction between H2O2 and O2•− (Haber–Weiss reaction)
  • Ascorbate can efficiently reduce free iron, thus recycling the cellular Fe(II)/Fe(III) to produce more OH• from H2O2 than can be generated during the Fenton reaction, which ultimately leads to lipid, protein, and DNA oxidation
  • Vit-C-stimulated iron absorption
  • reduce cellular iron efflux
  • high-dose Vit-C may elevate cellular LIP concentrations
  • ascorbate enhanced cancer cell LIP specifically by generating H2O2
  • Vit-C produces H2O2 extracellularly, which in turn inhibits tumor cells immediately
  • tumor cells have a need for readily available Fe(II) to survive and proliferate.
  • Tf has been recognized to sequester most labile Fe(II) in vivo
  • Asc•− and H2O2 were generated in vivo upon i.v Vit-C administration of around 0.5 g/kg of body weight and that the generation was Vit-C-dose reliant
  • free irons, especially Fe(II), increase Vit-C autoxidation, leading to H2O2 production
  • iron metabolism is altered in malignancies
  • increase in the expression of various iron-intake pathways or the downregulation of iron exporter proteins and storage pathways
  • Fe(II) ion in breast cancer cells is almost double that in normal breast tissues
  • macrophages in the cancer microenvironment have been revealed to increase iron shedding
  • Advanced breast tumor patients had substantially greater Fe(II) levels in their blood than the control groups without the disease
  • increased the amount of LIP inside the cells through transferrin receptor (TfR)
  • Warburg effect, or metabolic reprogramming,
  • Warburg effect is aided by KRAS or BRAF mutations
  • Vit-C is supplied, it oxidizes to DHA, and then is readily transported by GLUT-1 in mutant cells of KRAS or BRAF competing with glucose [46]. DHA is quickly converted into ascorbate inside the cell by NADPH and GSH [46,107]. This decrease reduces the concentration of cytosolic antioxidants and raises the intracellular ROS amounts
  • increased ROS inactivates glyceraldehyde 3-phosphate dehydrogenase (GAPDH)
  • ROS activates poly (ADP-ribose) polymerase (PARP), which depletes NAD+ (a critical co-factor of GAPDH); thus, further reducing the GAPDH associated with a multifaceted metabolic rewiring
  • Hindering GAPDH can result in an “energy crisis”, due to the decrease in ATP production
  • high-dose Vit-C recruited metabolites and increased the enzymatic activity in the pentose phosphate pathway (PPP), blocked the tri-carboxylic acid (TCA) cycle, and increased oxygen uptake, disrupting the intracellular metabolic balance and resulting in irreversible cell death, due to an energy crisis
  • mega-dose Vit-C influences energy metabolism by producing tremendous amounts of H2O2
  • Due to its great volatility at neutral pH [76], bolus therapy with mega-dose DHA has only transitory effects on tumor cells, both in vitro and in vivo.
Nathan Goodyear

Causative role of gut microbiota in non-alcoholic fatty liver disease pathogenesis - 0 views

www.ncbi.nlm.nih.gov/...PMC3481143

metabolic endotoxemia inflammation non-alcoholic fatty liver NAFLD gut bacteria fatty liver disease

shared by Nathan Goodyear on 14 Jan 13 - No Cached
  • Nathan Goodyear on 14 Jan 13
     
    metabolic endotoxemia plays role in NAFLD.  Gut bacterial balance plays a role in NAFLD.
Nathan Goodyear

A randomized, open-label, crossover study ... [Menopause. 2007 Nov-Dec] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17507833

BHRT HRT estrogen oral transdermal therapy treatment hormones TBG thyroid liver metabolism

shared by Nathan Goodyear on 16 Nov 11 - No Cached
  • Nathan Goodyear on 16 Nov 11
     
    oral estrogen is a bad choice as it relates to BHRT or HRT for that matter.  Compared to transdermal estrogen, oral estrogen through increasing TBG and slowed liver metabolism results in decreased thyroid hormone production.  
Nathan Goodyear

Association of serum lead and mercury level with cardiometabolic ri... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...25017868

ALT liver enzymes cholesterol blood pressure triglycerides metabolic syndrome lead Pb mercury Hg

shared by Nathan Goodyear on 09 Mar 15 - No Cached
  • Nathan Goodyear on 09 Mar 15
     
    study finds Pb and Hg associated with increased cardiometabolic risk factors.  Elevated liver enzymes found to be positively associated with serum Pb levels.  Metabolic Syndrome was found to be associated with higher Pb and Hg levels.
Nathan Goodyear

Role of Polymorphic Human Cytochrome P450 Enzymes in Estrone Oxidation - 0 views

cebp.aacrjournals.org/...551.long

estrogen metabolism estrogen metabolites cytochrome P450 estrogen estrone hormones detoxification metabolites

shared by Nathan Goodyear on 11 Sep 15 - No Cached
  • CYP1A1 and CYP1B1 are not expressed in any significant quantity in the liver. Therefore, they would not be expected to contribute to the overall systemic metabolism of estrone. However, both enzymes have been identified in breast tissue
  • CYP1A1 displayed relatively high activity for all three hydroxylations, suggesting that it may play an important role in extrahepatic tissues where it is expressed
  • CYP1A1 was more active with regard to 2-hydroxylation and 4-hydroxylation, it also displayed one of the greatest 16α-hydroxylating activities of the CYP enzymes tested.
  • ...4 more annotations...
  • CYP1B1 displayed a high affinity for estrone and preferentially catalyzed 4-hydroxylation over 2-hydroxylation
  • CYP1B1 did not seem to contribute to 16α-hydroxylation.
  • CYP1B1 was shown to preferentially catalyze 4-hydroxylation, whereas CYP1A1 was shown to preferentially catalyze 2-hydroxylation
  • Among the CYP enzymes expressed in the liver, CYP1A2 was the most active with regard to 2-hydroxylation
  • Nathan Goodyear on 11 Sep 15
     
    good discussion of estrogen metabolism and the P450 enzymes.
Nathan Goodyear

Levels of serum testosterone predict prevalent but not incident non... - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...25708291

Testosterone NAFLD non-alcoholic fatty liver liver disease men male hormone hormones

shared by Nathan Goodyear on 02 Mar 15 - No Cached
  • Nathan Goodyear on 02 Mar 15
     
    Lower Testosterone associated with increased prevalence of NAFLD in men.   Higher Testosterone levels did not reduce or reverse progression of NAFLD in men. This points to Testosterone as just one piece of the metabolic puzzle in metabolic syndrome, NAFLD... in men.  
‹ Previous 21 - 40 of 75 Next › Last »
Showing 20▼ items per page