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Nathan Goodyear

Toxicity of the spike protein of COVID-19 is a redox shift phenomenon: A novel therapeu... - 0 views

www.sciencedirect.com/...S0891584923005014

COVID19 COVID-19 cancer inflammation SARS-CoV-2 spike proteins COVID spikeopathy

shared by Nathan Goodyear on 01 Sep 23 - No Cached
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • Redox shift is due to Warburg effect and mitochondrial impairment.
  • ...88 more annotations...
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • The cytokine storm is a consequence of mitochondrial dysfunction
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • Lipoic acid, Methylene Blue and Chlorine dioxide relieve COVID-19 spike protein toxicity
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • most diseases display a form of anabolism due to mitochondrial impairment
  • infection by Covid-19 follows a similar pattern
  • chronic inflammation
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • Long-term effects include redox shift and cellular anabolism as a result of the Warburg effect and mitochondrial dysfunction
  • infection by Covid-19 follows a similar pattern
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • unrelenting anabolism leads to the cytokine storm,
  • chronic inflammation
  • chronic inflammation
  • infection by Covid-19 follows a similar pattern
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Lipoic acid and Methylene Blue have been shown to enhance the mitochondrial activity, relieve the Warburg effect and increase catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • Methylene Blue, Chlorine dioxide and Lipoic acid may help reduce long-term Covid-19 effects by stimulating the catabolism
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • direct consequence of redox iMeBalance, itself a consequence of decreased energy yield by the mitochondria
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • mitochondrial dysfunction and increased levels of lactate, which are important characteristics of metabolic shift and Warburg effect in many diseases
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • increased lactate dehydrogenase activity (LDH) was observed in COVID-19 patients
  • almost every disease presents an increased anabolism
  • almost every disease presents an increased anabolism
  • cell division is the most sophisticated way to release entropy
  • cell division is the most sophisticated way to release entropy
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Wow
  • transition from catabolism to anabolism is driven by a redox shift
  • transition from catabolism to anabolism is driven by a redox shift
  • viral spike protein binds to ACE2 receptor of the host cell [22,23].
  • redox signaling plays an important role in regulating immune function and inflammation, and disruptions in this signaling can lead to excessive cytokine production and immune system activation
  • Aging is associated with a poor control of the redox balance
  • thiol/disulfide homeostasis
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • reduced extracellular environment in the elderly and the increased susceptibility to Covid-19 infection
  • Redox signaling tightly modulates the inflammatory response and oxidative stress has been reported in acute Covid-19
  • People at high risk are the elderly, patients suffering from metabolic syndrome such as obesity, or those suffering from chronic diseases such as cancer or inflammation
  • COVID-19 patients with severe disease have higher levels of oxidative stress markers and lower antioxidant levels
  • oxidative stress can activate the NLRP3 inflammasome, which is a protein complex that plays a key role in the cytokine storm
  • inflammation leads to the formation of ROS and RNS, while redox iMeBalance results in cellular damage, which in turn triggers an inflammatory response
  • persistently elevated mtROS triggers endothelial dysfunction and inflammation, which results in a vicious loop involving ROS, inflammation, and mitochondrial dysfunction
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • Damaged mitochondria releasing ROS induce inflammation via the NLRP3 inflammasome
  • reduced environment during the cytokine storm
  • IL-2 is highly up-regulated in Covid-19 patients [37], and IL-2 is known to significantly stimulate the generation of NO in patients
  • Nitric acid is also the key mediator of IL-2-induced hypotension and vascular leak syndrome
  • mitochondrial dysfunction has been linked to the pathogenesis of Covid-19
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • mitochondrial dysfunction triggered by SARS-CoV-2 leads to damage to the mitochondria
  • As catabolism is decreased, entropy is released through anabolism
  • Elevated levels of lactate, a characteristic of the Warburg effect, were also reported in the high-risk Covid-19
  • elevated levels of ventricular lactic acid consistent with oxidative stress
  • A decrease of ΔΨm is implicated in several inflammation-related diseases
  • decrease in ΔΨm in leucocytes from Covid-19 patients
  • vaccinated with RNA or DNA vaccines triggering the synthesis of the viral spike protein in human cells
  • viral reactivation in varicella-zoster virus [55] or hepatitis [56], coagulopathy and resulting stroke and myocarditis following both DNA-based vaccines [57] and RNA-based vaccines
  • Covid-19, mitochondrial impairment
  • characteristic of the Warburg effect is present in almost every disease and appears to be a central feature in most of the hallmarks of cancer
  • inflammation, mitochondrial dysfunction and increased lactate concentrations in the extracellular fluid
  • In Covid-19, like any inflammation, there is a metabolic rewiring where cells rely on glycolysis
  • As the mitochondria are impaired, the infected cell cannot catabolize efficiently. It will release lactic acid in the blood stream
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Mitochondrial impairment
  • Striking similarities are seen between cancer, Alzheimer's disease and Covid-19, all related to the Warburg effect
  • Cancer, inflammation, Alzheimer's, and Parkinson's diseases share a common peculiarity, the inability of the cell to export entropy outside the body in the harmless form of heat
    • Nathan Goodyear
      Nathan Goodyear on 01 Sep 23
       
      Entropy: lack of order or predictability; gradual decline into disorder.
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB relieves the Warburg effect [87], improves memory [77], is active in the treatment of depressive episodes [79,80] and reduces the importance of ischemic strokes
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • MEB has been shown to inhibit SARS-Cov-2 replication in vitro
  • It has been shown that Covid-19-patients treated with MEB, have a significant reduction in hospital stay duration and mortality
  • MeB is an acceptor-donor molecule
  • MeB + can take a pair of electrons (of H atoms) and MeBH can release this pair easily, so that MeB is partially recycled like a catalyst
  • MeB acts as an electron bridge between a donor (FADH2, FMNH, NADH) and an acceptor (complex IV of ETC or oxygen itself)
  • As a coenzyme of pyruvate dehydrogenase (PDH), alpha-lipoic acid (ALA) initiates the formation of acetyl-CoA to feed the TCA cycle
  • ALA enhances the catabolism of carbon. cycle and therefore may reduce the Warburg effect and consequently, lactate production
  • Methylene Blue plays a similar role after the TCA cycle, by carrying electrons to complex IV of the electron transport chain
  • Drugs such as lipoic acid and MeB, which target the metabolism, decrease the redox shift by increasing catabolism
Nathan Goodyear

Branched Chain Amino Acid Supplementation for Patients with Cirrhosis | Clinical Correl... - 0 views

www.clinicalcorrelations.org/?p=3544

BCCA branched chain amino acids liver cirrhosis hepatitis amino acids

shared by Nathan Goodyear on 05 Oct 15 - No Cached
  • low level of BCAAs in patients with cirrhosis is hypothesized to be one of multiple factors responsible for development of hepatic encephalopathy
  • supplementation of BCAAs is thought to facilitate ammonia detoxification by supporting synthesis of glutamine, one of the non-branched chain amino acids, in skeletal muscle and in the brain as well as diminishing the influx of AAAs across the blood-brain barrier
  • oral BCAA supplementation is more useful in chronic encephalopathic patients than is parenteral BCAA supplementation in patients with acute encephalopathy
  • ...35 more annotations...
  • malnutrition progressing to cachexia is another common manifestation of cirrhosis
  • Malnutrition can be mitigated with BCAA supplementation
  • Studies show that administration of amino acid formulas enriched with BCAAs can reduce protein loss, support protein synthesis, and improve nutritional status of patients with chronic liver disease
  • Leucine has been shown to be the most effective of the BCAAs because it acts via multiple pathways to stimulate protein synthesis
  • BCAAs metabolites inhibit proteolysis
  • Patients with cirrhosis have both insulin deficiency and insulin resistance
  • BCAAs (particularly leucine) help to reverse the catabolic, hyperglucagonemic state of cirrhosis both by stimulating insulin release from the pancreatic β cells and by decreasing insulin resistance allowing for better glucose utilization
  • Coadministration of BCAAs and glucose has been found to be particularly useful
  • BCAA supplementation improves protein-energy malnutrition by improving utilization of glucose, thereby diminishing the drive for proteolysis, inhibiting protein breakdown, and stimulating protein synthesis
  • Cirrhotic patients have impaired immune defense, characterized by defective phagocytic activity and impaired intracellular killing activity
  • another effect of BCAA supplementation is improvement of phagocytic function of neutrophils and possibly improvement in natural killer T (NKT) cell lymphocyte activity
  • BCAA supplementation may reduce the risk of infection in patients with advanced cirrhosis not only through improvement in protein-energy malnutrition but also by directly improving the function of the immune cells themselves
  • BCAA administration has also been shown to have a positive effect on liver regeneration
  • A proposed mechanism for improved liver regeneration is the stimulatory effect of BCAAs (particularly leucine) on the secretion of hepatocyte growth factor by hepatic stellate cells
  • BCAAs activate rapamycin signaling pathways which promotes albumin synthesis in the liver as well as protein and glycogen synthesis in muscle tissue
  • Chemical improvement with BCAA treatment is demonstrated by recovery of serum albumin and lowering of serum bilirubin levels
  • long-term oral BCAA supplementation was useful in staving off malnutrition and improving survival by preventing end-stage fatal complications of cirrhosis such as hepatic failure and gastrointestinal bleeding
  • The incidence of death by any cause, development of liver cancer, rupture of esophageal varices, or progression to hepatic failure was decreased in the group that received BCAA supplementation
  • Patients receiving BCAA supplementation also have a lower average hospital admission rate, better nutritional status, and better liver function tests
  • patients taking BCAA supplementation report improved quality of life
  • BCAAs have been shown to mitigate hepatic encephalopathy, cachexia, and infection rates, complications associated with the progression of hepatic cirrhosis
  • BCAAs make up 20-25% of the protein content of most foods
  • Highest levels are found in casein whey protein of dairy products and vegetables, such as corn and mushrooms. Other sources include egg albumin, beans, peanuts and brown rice bran
  • In addition to BCAAs from diet, oral supplements of BCAAs can be used
  • Oral supplementation tends to provide a better hepatic supply of BCAAs for patients able to tolerate PO nutrition as compared with IV supplementation, especially when treating symptoms of hepatic encephalopathy
  • Coadministration of BCAAs with carnitine and zinc has also been shown to increase ammonia metabolism further reducing the encephalopathic symptoms
  • Cirrhotic patients benefit from eating frequent, small meals that prevent long fasts which place the patient in a catabolic state
  • the best time for BCAA supplementation is at bedtime to improve the catabolic state during starvation in early morning fasting
  • A late night nutritional snack reduces symptoms of weakness and fatigability, lowers postprandial hyperglycemia, increases skeletal muscle mass,[25] improves nitrogen balance, and increases serum albumin levels.[26] Nocturnal BCAAs even improve serum albumin in cirrhotic patients who show no improvement with daytime BCAAs
  • Protein-energy malnutrition (PEM), with low serum albumin and low muscle mass, occurs in 65-90% of cases of advanced cirrhosis
  • hyperglucagonemia results in a catabolic state eventually producing anorexia and cachexia
  • BCAAs are further depleted from the circulation due to increased uptake by skeletal muscles that use the BCAAs in the synthesis of glutamine, which is produced in order to clear the ammonia that is not cleared by the failing liver
  • patients with chronic liver disease, particularly cirrhosis, routinely have decreased BCAAs and increased aromatic amino acids (AAAs) in their circulation
  • Maintaining a higher serum albumin in patients with cirrhosis is associated with decreased mortality and improved quality of life
  • the serum BCAA concentration is strongly correlated with the serum albumin level
  • Nathan Goodyear on 05 Oct 15
     
    great review of cirrhosis and BCCA supplementation.
Nathan Goodyear

Using testosterone and cortisol as bioma... [J Strength Cond Res. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...25144130

Total Testosterone cortisol testosterone:cortisol hormone hormones performance exercise stress

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    Study followed Total Testosterone:Cortisol ratios to monitor catabolic/anabolic states in basketball players.  The authors followed serum levels and monitored them 24-36 hours post game.  Those playing > 25 min/game had the lowest TT:C and highest cortisol indicating a catabolic state and making recovery critical.
Nathan Goodyear

Changes in cortisol and testostero... [J Sports Med Phys Fitness. 2000] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...11034434

anabolic catabolic long endurance training competition T:C testosterone cortisol sports athlete athletics

shared by Nathan Goodyear on 19 Feb 13 - No Cached
  • Nathan Goodyear on 19 Feb 13
     
    long endurance competitive events associated with catabolic hormone balances found in a low T:C ratio.  This occurs primarily through an elevation in cortisol and small drop in Testosterone.  The recovery phase is anabolic through a rise in T:C, primarily through a return to baseline by cortisol and an increase in Testosterone.
Nathan Goodyear

Saliva cortisol, testosterone and T/C ratio... [Int J Sports Med. 1999] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10190771

saliva salivary Testosterone athletes cortisol catabolic sports recovery T:C ratio

shared by Nathan Goodyear on 25 Apr 12 - No Cached
  • Nathan Goodyear on 25 Apr 12
     
    this study looked at salivary testosterone and cortisol in exercise recovery.  They found a low T/C ratio in this athletes.  This is a catabolic state.  A normalization of the a low T/C ratio will increase muscle recovery and should improve performance.  Testing was with saliva
Nathan Goodyear

The anticatabolic and wound healing effects of t... [J Crit Care. 2000] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...10757193

androgen Testosterone surgery healing

shared by Nathan Goodyear on 10 Dec 13 - No Cached
  • Nathan Goodyear on 10 Dec 13
     
    In catabolic states, such as in burn injuries, anabolic steroids such as a synthetic anabolic agent (oxandrolone) improves recovery.  This could be easily extrapolated to androgens in general.
Nathan Goodyear

Update on branched-chain amino acid supplementation in liver... : Current Opinion in Ga... - 0 views

journals.lww.com/...nched_chain_amino_acid.12.aspx

branched chain amino acids liver cirrhosis hepatitis amino acids protein BCCA

shared by Nathan Goodyear on 05 Oct 15 - No Cached
  • Nathan Goodyear on 05 Oct 15
     
    Branched chain amino acids for those with liver cirrhosis.  This is deficiency is due to the hyperglucoganemia that results from the catabolic metabolism.  It is interesting that peripheral metabolism also sets up.  
Nathan Goodyear

Branched-chain amino acids as a protein- and energy-source in liver cirrhosis. - PubMed... - 0 views

www.ncbi.nlm.nih.gov/...14684176

BCAA branched chain amino acids liver cirrhosis hepatitis ammonia

shared by Nathan Goodyear on 05 Oct 15 - No Cached
  • Nathan Goodyear on 05 Oct 15
     
    BCAA for liver cirrhosis to improve ammonia clearance.  Increased glutamine is a means to compensate for the decreased ammonia clearance as well as a means to improve energy balance often present in these clients.  Night time dosing prevents fasting catabolic exacerbations.
Nathan Goodyear

Dose effects of caffeine ingestion... [J Sports Med Phys Fitness. 2014] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...24867603

caffeine sports fitness resistance training cortisol Testosterone male hormone hormones insulin sensitivity

shared by Nathan Goodyear on 03 Jun 14 - No Cached
  • Nathan Goodyear on 03 Jun 14
     
    high caffeine intake found to be associated with increased Testosterone and cortisol pre and post resistance work out times.  An elevated Testosterone would be good at both points.  However, an elevated cortisol would be catabolic during the recovery phase.  The study also found a decrease in insulin sensitivity with high caffeine intake.  This was improved with moderate and low intake.
Nathan Goodyear

Mitochondrial Fission Induces Glycolytic Reprogramming in Cancer-Associated Myofibrobla... - 0 views

www.ncbi.nlm.nih.gov/...PMC3478457

warburg effect Cancer cancer associated fibroblasts CAFs reverse warburg effect lactate aerobic glycolysis mitochondria oxidative stress ROS H2O2

shared by Nathan Goodyear on 11 Nov 14 - No Cached
  • L-lactate functions as an onco-metabolite, stimulating mitochondrial biogenesis and OXPHOS in adjacent cancer cells, directly providing energy for tumor growth
  • Oxidative stress in stromal fibroblasts then induces their metabolic conversion into cancer-associated fibroblasts. Such oxidative stress drives the onset of autophagy, mitophagy, and aerobic glycolysis in fibroblasts, resulting in the local production of high-energy mitochondrial fuels (such as L-lactate, ketone bodies, and glutamine). These recycled nutrients are then transferred to cancer cells, where they are efficiently burned via oxidative mitochondrial metabolism (OXPHOS)
  • stromal L-lactate serves as a high-energy mitochondrial “fuel” for cancer cells. We have termed this new model of cancer metabolism “Two-Compartment Tumor Metabolism”, where two opposing metabolic compartments co-exist, side-by-side, with stromal glycolysis fueling OXPHOS in cancer cells
  • ...10 more annotations...
  • Two-Compartment Tumor Metabolism
  • Reverse Warburg Effect”, is that catabolic fibroblasts should promote tumor growth, without any increases in angiogenesis
  • when cancer cells use L-lactate as a mitochondrial fuel source, this metabolic phenotype is a predictor of lethal cancer metabolism
  • tumor microenvironment is intimately involved in tumor development and progression
  • mitochondrial dysregulation is likely the “root cause” of several human disease(s), and especially epithelial cancers
  • Both in vitro and in vivo studies have now provided convincing evidence that “activated” stromal fibroblasts, a.k.a., myofibroblasts, may play a critical role in initiating tumor recurrence, via paracrine interactions with adjacent tumor epithelial cells
  • A new hypothesis is that cancer is not a cell autonomous disease, but rather a disease of the tumor microenvironment
  • cancer cells behave as metabolic parasites, by inducing oxidative stress in adjacent normal fibroblasts
  • recent experimental evidence indicates that cancer-associated fibroblasts have a catabolic phenotype, and undergo autophagy and mitophagy, resulting in the onset of glycolytic metabolism, driving L-lactate production, and its release into the tumor microenvironment
  • oncogenic mutations in cancer cells lead to ROS production and the “secretion” of hydrogen peroxide species
  • Nathan Goodyear on 11 Nov 14
     
    A good discussion of what is proposed the Reverse Warburg effect.  A process by which the local environment dictates tumor progression.  The cancer cells release ROS primarily in the form of H2O2 and this leads to Cancer Associated Fibroblasts (CAFs) in the stroma.  The altered stromal environment increases ROS further and promotes ocogenic metabolites through the classic Warburg effect.  This high lactate production from the CAFs then is used by the cancer cells via classic oxidative phosphorylation.  Complex, beautiful and still an the understanding is a work in progress.   This study/article points to the importance of oxidative stress in some cancer development through CAFs.
Nathan Goodyear

Blood Hormones as Markers of Training Stress and Overtraining | SpringerLink - 0 views

link.springer.com/...00007256-199520040-00004

OTS overtraining syndrome hormones Testosterone cortisol

shared by Nathan Goodyear on 14 Mar 18 - No Cached
  • Nathan Goodyear on 14 Mar 18
     
    Older article, but good one still on hormones and overtraining.  Look to the Testosterone/Cortisol ratio.  OTS will lead to decreased Testosterone and increased cortisol resulting in chronic catabolic state.
Nathan Goodyear

Overtraining Syndrome - 0 views

www.ncbi.nlm.nih.gov/...PMC3435910

overtraining syndrome OTS exercise athletes cortisol adrenals Testosterone Testosterone:Cortisol hormones

shared by Nathan Goodyear on 29 Jan 16 - No Cached
  • Alterations in the HPA and hypothalamic-pituitary-gonadal axes with a resultant decrease in testosterone:cortisol ratios have been implicated in OTS. Proinflammatory cytokines are potent activators of the HPA system, which cause release of corticotropin-releasing hormone, adrenocorticotropic hormone, and cortisol. These cytokines suppress testosterone through central inhibition
  • Some have suggested that a decreased testosterone:cortisol ratio can be diagnostic of NFO and/or OTS. However, the ratio represents the physiologic strain of training rather than the athlete’s maladaption to that stress
  • Cortisol (catabolic and anti-inflammatory) is converted to inactive cortisone by 11β-HSD2
  • ...2 more annotations...
  • A prospective study found a clinically significant increase in overnight urinary cortisol:cortisone ratio during a high training load period in triathletes, who subsequently underperformed and reported fatigue
  • It is proposed that cytokines may inhibit 11β-HSD2 activity and result in relative increases in cortisol and, hence, catabolism
  • Nathan Goodyear on 29 Jan 16
     
    Overtraining syndrome described.
Nathan Goodyear

ScienceDirect.com - Cell Metabolism - Estrogen Receptors and the Metabolic Network - 0 views

www.sciencedirect.com/...S1550413111003123

ER-alpha ER-beta estrogen receptor receptors metabolic syndrome MetS hormone hormones

shared by Nathan Goodyear on 11 Oct 12 - No Cached
  • The pro-opiomelanocortin (POMC) neurons have an anorexigenic action and, when activated, reduce food intake through the release of two peptides, α-melanocyte-stimulating hormone (α-MSH) and cocaine-and-amphetamine-regulated transcripts (CART). The neuropeptide Y (NPY) neurons, on the other hand, release NPY hormone and agouti gene-related protein (AgRP), which prevent the binding of α-MSH to MC3R and MC4R, increasing food intake
  • This suggests that the central anorexic effects of E2 may occur via ERβ
  • The main hypothalamic areas involved in food intake and satiety are the arcuate nucleus (ARC), the lateral hypothalamus (LH), the paraventricular nucleus (PVN), the ventromedial hypothalamus (VMH), and the dorsomedial hypothalamus (DMH)
  • ...22 more annotations...
  • Leptin is a potent anorexigenic and catabolic hormone secreted by adipose cells that reduces food intake and increases energy expenditure
  • E2 not only modulates leptin receptor mRNA in the ARC and VMH, but also increases hypothalamic sensitivity to leptin, altering peripheral fat distribution
  • ghrelin. It acts on growth hormone secretagogue receptors (GHSR1a) located in the ARC and is a potent stimulator of food intake
  • It thus appears that of the two ERs, ERα plays a predominant role in the CNS regulation of lipid and carbohydrate homeostasis.
  • Both ERs have been identified in the ARC
  • Stimulation of MCH neurons increases food intake and fat accumulation while its inhibition leads to decreased food intake and reduced fat accumulation.
  • Both ERs have been identified in the LH
  • both ERs have been identified in this nucleus
  • The PVN is the region of the hypothalamus with the highest expression of ERβ and is reported to be weakly ERα positive
  • The VMH is ERα regulated
  • Skeletal muscle is responsible for 75% of the insulin-induced glucose uptake in the body
  • GLUT4 is highly expressed in muscle and represents a rate-limiting step in the insulin-induced glucose uptake
  • data suggest that in the physiological range, E2 is beneficial for insulin sensitivity, whereas hypo- or hyperestrogenism is related to insulin resistance
  • In aging female rats, E2 treatment improves glucose homeostasis mainly through its ability to increase muscle GLUT4 content on the cell membrane
  • It is evident that ERα and ERβ have distinct actions and that much more research is needed to clearly identify the function of each receptor in muscle.
  • E2 prevents accumulation of visceral fat, increases central sensitivity to leptin, increases the expression of insulin receptors in adipocytes, and decreases the lipogenic activity of lipoprotein lipase in adipose tissue
  • In rats, ovariectomy increases body weight, intra-abdominal fat, fasting glucose and insulin levels, and insulin resistance followed by decreased phosphorylation of AMPK and its substrate acetyl-CoA carboxylase in adipose tissue
  • decreased adiponectin, PPARγ coactivator-1α (PGC-1α), and uncoupling protein 2 (UCP2) and increased resistin
  • Men with aromatase deficiency have truncal obesity, elevated blood lipids, and severe insulin resistance
  • Although not all studies are in agreement, polymorphisms of ERα in humans have been associated with risk factors for CVDs
  • Human subcutaneous and visceral adipose tissues express both ERα and ERβ, whereas only ERα mRNA has been identified in brown adipose tissue
  • suggesting that ERα is the main regulator of GLUT4 expression in adipose tissue
  • Nathan Goodyear on 11 Oct 12
     
    very nice article that looks at the balance of ER-alpha/ER-beta and their role in metabolic syndrome.  This article discusses the balance of  these receptors are tissue dependent in their effect.  I like their conclusion: "...but these mechanisms will never be completely understood if they are not considered in the context of a whole system.
Nathan Goodyear

Intratumoral androgen biosynthesis in prostate cancer pathogenesis and response to therapy - 0 views

erc.endocrinology-journals.org/...R175.full

prostate cancer DHT 3-beta-diol 3-alpha-diol metabolites metabolite male men hormone hormones androgen deprivation therapy

shared by Nathan Goodyear on 03 Feb 14 - No Cached
  • Additional studies have similarly found that prostate tissue levels of DHT in PCa patients treated with ADT therapy before prostatectomy declined by only ∼75% versus declines of ∼95% in serum levels
  • In a recent study in healthy men, treatment for 1 month with a GnRH antagonist to suppress testicular androgen synthesis caused a 94% decline in serum testosterone, but only a 70–80% decline in prostate tissue testosterone and DHT
  • progression to CRPC was associated with increased intratumoral accumulation or synthesis of testosterone.
  • ...9 more annotations...
  • the intraprostatic synthesis of testosterone from adrenal-derived precursors likely accounts for the relatively high testosterone levels in prostate after ADT
  • In addition, AR activity in these cells is likely further enhanced by multiple mechanisms that sensitize AR to low levels of androgens
  • higher affinity ligand DHT (approximately eightfold higher affinity
  • type 2 5α-reductase (SRD5A2) being the major enzyme in prostate
  • reduce DHT to 5α-androstane-3α,17β-diol (3α-androstanediol; Ji et al. 2003, Rizner et al. 2003), which is then glucuronidated to form 3α-androstanediol glucuronide by the enzymes UDP glycosyltransferase 2, B15 (UGT2B15) or UGT2B17
  • DHT in prostate is inactivated by the enzyme AKR1C2, which is also termed 3α-hydroxysteroid dehydrogenase type 3 (3α-HSD type 3
    • Nathan Goodyear
      Nathan Goodyear on 03 Feb 14
       
      The metabolite 3-alpha androstanediol is NOT inactive as this author states.  This DHT metabolite actually can stimulate  ER alpha receptors in the prostate.
  • AKR1C1, is also expressed in prostate. However, in contrast to AKR1C2, it converts DHT primarily to 5α-androstane-3β,17β-diol (3β-androstanediol; Steckelbroeck et al. 2004), which is a potential endogenous ligand for the estrogen receptor β
  • Significantly, intraprostatic testosterone levels were not substantially reduced relative to controls with normal serum androgen levels, although DHT levels were reduced to 18% of controls
  • testosterone levels in many of the CRPC samples were actually increased relative to control tissues (Montgomery et al. 2008). While DHT levels were less markedly increased, this may have reflected DHT catabolism
  • Nathan Goodyear on 03 Feb 14
     
    This article discusses the failure of androgen deprivation therapy and prostate cancer.  This failure is quite common.  The authors point to alpha-DHT as the primary mechanism through AR stimulation.  However, we know that DHT metabolites also stimulate estrogen receptors.
Nathan Goodyear

The Androgen Derivative 5α-Androstane-3β,17β-Diol Inhibits Prostate Cancer Ce... - 0 views

cancerres.aacrjournals.org/...5445.full

prostate cancer 3-beta androstanediol DHT metabolite E-cadherin ER beta ER-beta male hormone hormones men

shared by Nathan Goodyear on 27 Jan 14 - No Cached
  • In the early stages, prostate cancer growth is dependent on circulating androgens
    • Nathan Goodyear
      Nathan Goodyear on 27 Jan 14
       
      This is in contrast to studies that show poor prognosis with Lower T at time of diagnosis of prostate cancer
  • 5α-reductase not only provides a potent amplification of the androgenic signal ( 4– 6), but it also prevents estrogen formation by subtracting testosterone from the action of aromatase ( 7, 8), thus blocking activation of the estrogen receptor subtypes (ERα and ERβ; refs. 9, 10)
  • ERβ is the prevailing subtype ( 11), and a growing body of evidence points to the protective role of this receptor in prostate cancer
  • ...3 more annotations...
  • It has been shown that the transformation of the dihydrotestosterone to 5α-androstane-3α,17β-diol (3α-diol) and 5α-androstane-3β,17β-diol (3β-Adiol), generates two metabolites unable to bind the androgen receptor, but possessing a very high affinity for the estrogen receptors
  • the effects of testosterone may result from the balance between the androgenic and the estrogenic molecules originating from its catabolism.
  • Recent data have been published postulating a direct estrogenic role of the 3β-hydroxylated derivatives of dihydrotestosterone in the prostate development and homeostasis
  • Nathan Goodyear on 27 Jan 14
     
    Here is the full article.
Nathan Goodyear

Nutrition & Metabolism | Full text | Fructose, insulin resistance, and metabolic dyslip... - 0 views

www.nutritionandmetabolism.com/...5

fructose metabolic syndrome metabolic syndrome insulin resistance obesity nutrition metabolism

shared by Nathan Goodyear on 16 Sep 13 - Cached
  • For thousands of years humans consumed fructose amounting to 16–20 grams per day
  • daily consumptions amounting to 85–100 grams of fructose per day
  • Of key importance is the ability of fructose to by-pass the main regulatory step of glycolysis, the conversion of glucose-6-phosphate to fructose 1,6-bisphosphate, controlled by phosphofructokinase
  • ...29 more annotations...
  • Thus, while glucose metabolism is negatively regulated by phosphofructokinase, fructose can continuously enter the glycolytic pathway. Therefore, fructose can uncontrollably produce glucose, glycogen, lactate, and pyruvate, providing both the glycerol and acyl portions of acyl-glycerol molecules. These particular substrates, and the resultant excess energy flux due to unregulated fructose metabolism, will promote the over-production of TG (reviewed in [53]).
  • Glycemic excursions and insulin responses were reduced by 66% and 65%, respectively, in the fructose-consuming subjects
  • reduction in circulating leptin both in the short and long-term as well as a 30% reduction in ghrelin (an orexigenic gastroenteric hormone) in the fructose group compared to the glucose group.
  • A prolonged elevation of TG was also seen in the high fructose subjects
  • Both fat and fructose consumption usually results in low leptin concentrations which, in turn, leads to overeating in populations consuming energy from these particular macronutrients
  • Chronic fructose consumption reduces adiponectin responses, contributing to insulin resistance
  • A definite relationship has also been found between metabolic syndrome and hyperhomocysteinemia
  • the liver takes up dietary fructose rapidly where it can be converted to glycerol-3-phosphate. This substrate favours esterification of unbound FFA to form the TG
  • Fructose stimulates TG production, but impairs removal, creating the known dyslipidemic profile
  • the effects of fructose in promoting TG synthesis are independent of insulinemia
  • Although fructose does not appear to acutely increase insulin levels, chronic exposure seems to indirectly cause hyperinsulinemia and obesity through other mechanisms. One proposed mechanism involves GLUT5
  • If FFA are not removed from tissues, as occurs in fructose fed insulin resistant models, there is an increased energy and FFA flux that leads to the increased secretion of TG
  • In these scenarios, where there is excess hepatic fatty acid uptake, synthesis and secretion, 'input' of fats in the liver exceed 'outputs', and hepatic steatosis occurs
  • Carbohydrate induced hypertriglycerolemia results from a combination of both TG overproduction, and inadequate TG clearance
  • fructose-induced metabolic dyslipidemia is usually accompanied by whole body insulin resistance [100] and reduced hepatic insulin sensitivity
  • Excess VLDL secretion has been shown to deliver increased fatty acids and TG to muscle and other tissues, further inducing insulin resistance
  • the metabolic effects of fructose occur through rapid utilization in the liver due to the bypassing of the regulatory phosphofructokinase step in glycolysis. This in turn causes activation of pyruvate dehydrogenase, and subsequent modifications favoring esterification of fatty acids, again leading to increased VLDL secretion
  • High fructose diets can have a hypertriglyceridemic and pro-oxidant effect
  • Oxidative stress has often been implicated in the pathology of insulin resistance induced by fructose feeding
  • Administration of alpha-lipoic acid (LA) has been shown to prevent these changes, and improve insulin sensitivity
  • LA treatment also prevents several deleterious effects of fructose feeding: the increases in cholesterol, TG, activity of lipogenic enzymes, and VLDL secretion
  • Fructose has also been implicated in reducing PPARα levels
  • PPARα is a ligand activated nuclear hormone receptor that is responsible for inducing mitochondrial and peroxisomal β-oxidation
  • decreased PPARα expression can result in reduced oxidation, leading to cellular lipid accumulation
  • fructose diets altered the structure and function of VLDL particles causing and increase in the TG: protein ratio
  • LDL particle size has been found to be inversely related to TG concentration
  • therefore the higher TG results in a smaller, denser, more atherogenic LDL particle, which contributes to the morbidity of the metabolic disorders associated with insulin resistance
  • High fructose, which stimulates VLDL secretion, may initiate the cycle that results in metabolic syndrome long before type 2 diabetes and obesity develop
  • A high flux of fructose to the liver, the main organ capable of metabolizing this simple carbohydrate, disturbs normal hepatic carbohydrate metabolism leading to two major consequences (Figure 2): perturbations in glucose metabolism and glucose uptake pathways, and a significantly enhanced rate of de novo lipogenesis and TG synthesis, driven by the high flux of glycerol and acyl portions of TG molecules coming from fructose catabolism
  • Nathan Goodyear on 16 Sep 13
     
    Fructose and metabolic syndrome.  Good discussion of the impact of high fructose intake and metabolic dysfunction.  This study also does a great job of highlighting the historical change of fructose intake.
Nathan Goodyear

Mechanisms dependent on tryptophan catabolism regulate immune responses in pr... - 0 views

www.ncbi.nlm.nih.gov/...PMC1809473

Sjogren sjögren syndrome autoimmune disease Tryptophan metabolism IDO disordered

shared by Nathan Goodyear on 30 Oct 13 - No Cached
  • Nathan Goodyear on 30 Oct 13
     
    Disordered Tryptophan metabolism is a useful biomarker for those with Sjogren's syndrome.  This study found an increased degradation of Tryptophan and increased IDO activity that correlated with increased severity of Sjogren's syndrome.
Nathan Goodyear

[Protein catabolism and malnutrition in liver cirrhosis - impact of oral nutritional th... - 0 views

www.ncbi.nlm.nih.gov/...20607635

BCAA branched chain amino acids liver cirrhosis amino acids

shared by Nathan Goodyear on 05 Oct 15 - No Cached
  • Nathan Goodyear on 05 Oct 15
     
    Patients with liver cirrhosis will have low BCAA and thus supplementation proves to improve survival and QOL measures.
Nathan Goodyear

Thyroid Hormone Concentrations, Disease, Physical Function, and Mortality in Elderly Me... - 0 views

jcem.endojournals.org/...6403

hormone thyroid concentrations rT3 reverse T3 hypothyroid hypothyroidism

shared by Nathan Goodyear on 08 Mar 11 - No Cached
  • High serum rT3 may result from a decreased peripheral metabolism of thyroid hormones due to the aging process itself and/or disease and may reflect a catabolic state.
  • Nathan Goodyear on 08 Mar 11
     
    elevated serum rT3 indicates tissue hypothyroidism; very different than rT3 in the pituitary, where high concentrations accumulate
Nathan Goodyear

Urinary estrogen metabolites in women at high risk for breast cancer - 0 views

carcin.oxfordjournals.org/...1532.full

breast cancer CA estrogen metabolism 2:16 OHE 2-OH-estrone 16-alpha-OH-estrone

shared by Nathan Goodyear on 10 May 12 - No Cached
  • obesity has also been linked to preferential estrogen metabolism via the 16-alpha-hydroxylation pathway; thus, a prediction of the mechanism by which obesity could increase breast cancer risk would be through a lowering of the 2:16 ratio in favor of the 16 pathway
  • increased BMI was associated with a lower 2:16 OHE ratio
  • Our data show a significant association between alcohol use, defined as at least one drink per day or an average of seven per week, and 2:16 OHE ratio
  • ...10 more annotations...
  • An alcohol-induced rise in estrogens as a consequence of alcohol catabolism in the liver has been reported
  • The only study that looked at the association between alcohol and wine consumption in healthy women did not report a clear association
  • smoking has been reported to increase induction of the 2-hydroxylation metabolic pathway (24). However, the few epidemiological studies conducted on healthy women showed no difference in estrogen metabolites with smoking status (22) or smoking dose (20), in line with our findings.
  • Family history of a first-degree family member with breast cancer confers a 2- to 4-fold risk of developing breast cancer
  • 16% of breast cancers are due to unidentified hereditary factors
  • Estrogen metabolism occurs through enzymes whose activity is determined by the presence of specific genetic polymorphisms, thus can be defined as unique to each individual.
  • the metabolism is also influenced by a number of environmental factors, which change over a lifetime
  • significantly lower 2:16 OHE ratio in women who have known breast cancer risk factors compared with healthy women
  • There was an additional significant association specifically with BMI and alcohol use, which also supports the evidence that these factors affect estrogen metabolism
  • Profiling estrogen metabolites may identify women who are more likely to develop breast cancer within a population of women with known risk factors
  • Nathan Goodyear on 10 May 12
     
    urinary estrogen metabolites shown to provide insight into breast cancer risk.  This study suggested that a low 2:16 OHE ratio increase breast cancer risk.
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