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Nathan Goodyear

Leptin serves body as energy signal | Harvard Gazette - 0 views

news.harvard.edu/...n-serves-body-as-energy-signal

leptin body energy hormones thyroid

shared by Nathan Goodyear on 08 Mar 11 - No Cached
  • replacing leptin to physiologically normal levels during fasting fully restored testosterone to baseline, indicating that leptin regulates the hypothalamic-pituitary- gonadal axis that controls the release of testosterone and estrogen
  • Leptin clearly has some effect on the thyroid hormone axis,
  • including thyroid-stimulating hormone and the free-circulating form of thyroid
  • Nathan Goodyear on 08 Mar 11
     
    Leptin regulates hypothalamic-pituitary axis; and don't forget thyroid too.
Nathan Goodyear

Determinants of intramyocellular triglyceride turnover: implications for insulin sensitivity - 0 views

ajpendo.physiology.org/...E203.full

insulin sensitivity resistance energy triglycerides

shared by Nathan Goodyear on 24 May 11 - No Cached
  • Nathan Goodyear on 24 May 11
     
    insulin sensitivity, triglyceride turnover and energy
Nathan Goodyear

Mitochondrial Fission Induces Glycolytic Reprogramming in Cancer-Associated Myofibroblasts, Driving Stromal Lactate Production, and Early Tumor Growth - 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

BMC Cancer | Full text | A lactate shuttle system between tumour and stromal cells is associated with poor prognosis in prostate cancer - 0 views

www.biomedcentral.com/...352

cancer prostate cancer CAFs cancer associated fibroblasts mono-carboxylate transporters

shared by Nathan Goodyear on 12 Nov 14 - No Cached
  • Under hypoxic conditions, tumour cells primarily use glycolysis for energy, producing lactate, which is expelled to the tumour microenvironment, allowing tumours to continue their glycolytic activity
  • Sonveaux et al. showed that lactate, which is generally considered a waste product, is preferred over glucose by oxidative tumour cells as their primary energy source
  • MCT4 is a low-affinity transporter, which is abundant in highly glycolytic muscle cells and is one of the many target genes of hypoxia-inducible factor 1 alpha (HIF-1α)
  • ...8 more annotations...
  • Other targets of HIF-1α include glucose transporter-1 (GLUT-1), the main transporter involved in glucose uptake [9,10]; lactate dehydrogenase V (LDHV), which is responsible for the conversion of pyruvate into lactate; pyruvate dehydrogenase kinase isozyme 1 (PDK1), which is responsible for the phosphorylation and consequent inactivation of pyruvate dehydrogenase (PDH); and carbonic anhydrase IX (CAIX), a hypoxia-related protein involved in pH regulation [11]. Alpha-methylacyl-CoA racemase (AMACR), pristanoyl-CoA oxidase (ACOX-3) and D-bifunctional protein (DBP), are also important fatty acid oxidation-related proteins in prostate cancer
  • the essential role played by the cross-talk between stroma and epithelium in carcinogenesis and prostate cancer progression has been increasingly recognised
  • strong membranous expression of MCT1 was consistently observed in cancer cells, suggesting a role for MCT1 in the transport of lactate into tumour cells from the acidic extracellular matrix, suggesting that lactate might be used as a fuel by oxidative cancer cells.
  • Our hypothesis is in agreement with those of Fiaschi et al.[17], who describe the metabolic reprogramming of CAFs towards the Warburg phenotype as a result of contact with prostate cancer cells
  • Using in vitro studies, they showed lactate production and efflux by de novo expressed MCT4 in CAFs and also demonstrated that, upon contact with CAFs, prostate cancer cells were reprogrammed towards aerobic metabolism, with an increase in lactate uptake via the lactate transporter MCT1.
  • pharmacological inhibition of MCT1-mediated lactate uptake dramatically affected PCa cell survival and tumour outgrowth
  • In this model, “energy transfer” or “metabolic coupling” between the tumour stroma and epithelial cancer cells fuels tumour growth and metastasis via oxidative mitochondrial metabolism in anabolic cancer cells
  • the concomitant expression of MCT1 in tumour cells and MCT4 in fibroblasts in the same tissue is clinically significant, and associated with poor prognosis.
  • Nathan Goodyear on 12 Nov 14
     
    Study confirms the importance of the crosstalk between cancer cells and CAFs via MCTs in prostate cancer.
Nathan Goodyear

Mild Dehydration Affects Mood in Healthy Young Women - 0 views

jn.nutrition.org/...jn.111.142000.abstract

dehydration water headaches mood energy

shared by Nathan Goodyear on 05 Jan 16 - No Cached
  • Nathan Goodyear on 05 Jan 16
     
    dehydration effects mood, energy and headaches in women.
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

Testosterone, the male hormone connection: treating diabetes and heart disease. - 0 views

www.worldhealth.net/...thera6_ch7.pdf

testosterone low T low testosterone CVD cardiovascular disease diabetes insulin leptin ghrelin PAI-1 obesity adiponectin type II diabetes DM atherosclerosis

shared by Nathan Goodyear on 13 Nov 12 - No Cached
  • Nathan Goodyear on 13 Nov 12
     
    good, well referenced discussion of how Testosterone support for those with low T can improve Diabetes, insulin function, improve energy balance, and reduce cardiovascular disease risk. The discussion discusses many of the moving parts in how testosterone improves CVD risk.
obat sehat

Diabetes - 0 views

sehatobat.blogspot.com/...es-alami-solusi-mengatasi.html

obesity hormones disease

shared by obat sehat on 04 Dec 12 - No Cached
  • obat sehat on 04 Dec 12
     
    Insulin is a hormone produced by the pancreas to control blood sugar. Diabetes can be caused by too little insulin, resistance to insulin, or both. To understand diabetes, it is important to first understand the normal process by which food is broken down and used by the body for energy. Several things happen when food is digested: A sugar called glucose enters the bloodstream. Glucose is a source of fuel for the body. An organ called the pancreas makes insulin. The role of insulin is to move glucose from the bloodstream into muscle, fat, and liver cells, where it can be used as fuel. People with diabetes have high blood sugar because their body cannot move sugar into fat, liver, and muscle cells to be stored for energy. This is because either: Their pancreas does not make enough insulin Their cells do not respond to insulin normally Both of the above There are two major types of diabetes. The causes and risk factors are different for each type: Type 1 diabetes can occur at any age, but it is most often diagnosed in children, teens, or young adults. In this disease, the body makes little or no insulin. Daily injections of insulin are needed. The exact cause is unknown. Type 2 diabetes makes up most diabetes cases. It most often occurs in adulthood. However, because of high obesity rates, teens and young adults are now being diagnosed with it. Many people with type 2 diabetes do not know they have it. Gestational diabetes is high blood sugar that develops at any time during pregnancy in a woman who does not have diabetes. Diabetes affects more than 20 million Americans. Over 40 million Americans have pre-diabetes (which often comes before type 2 diabetes).
Nathan Goodyear

Salivary estradiol, interleukin-6 product... [Eur J Appl Physiol. 2011] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...21203888

saliva salivary E2 Estradiol IL-6 inflammation hormone hormones testing exercise females

shared by Nathan Goodyear on 05 Nov 12 - No Cached
  • Nathan Goodyear on 05 Nov 12
     
    In this study, in addition to Estradiol, IL-6 was followed via salivary testing. This study found that post-exercise IL-6 elevation reduced energy availability from fat stores.  
Nathan Goodyear

Orexin/Hypocretin: A Neuropeptide at the Interface of Sleep, Energy Homeostasis, and Reward System - 0 views

pharmrev.aspetjournals.org/...162.full

orexin orexins sleep energy

shared by Nathan Goodyear on 02 Jan 13 - No Cached
  • Nathan Goodyear on 02 Jan 13
     
    great read on orexins!  Orexins play a role in feeding and in sleep/wake cycle. Orexins interact with the limbic system to play a role in reward.
Nathan Goodyear

Plasticity in mitochondrial cristae density allows metabolic capacity modulation in human skeletal muscle - Nielsen - 2016 - The Journal of Physiology - Wiley Online Library - 0 views

onlinelibrary.wiley.com/...763493D2C50D44B6157B92C.f03t04

mitochondria exercise endurance exercise muscle

shared by Nathan Goodyear on 29 Nov 16 - No Cached
  • Nathan Goodyear on 29 Nov 16
     
    New study suggests endurance training can change mitochondria to improve energy production efficiency.
Nathan Goodyear

The Effects of Capsaicin and Capsiate on Energy Balance: Critical Review and Meta-analyses of Studies in Humans - 0 views

chemse.oxfordjournals.org/...103.short

capsaicin weight-loss overweight obesity capsiate metabolism energy balance

shared by Nathan Goodyear on 10 Feb 12 - No Cached
  • Nathan Goodyear on 10 Feb 12
     
    capsaicin shown to benefit weight loss.  Though just modestly.  But hey, anything to help.
Nathan Goodyear

The endocabbinoid system and the treatment of obesity - 0 views

diabesity.eu/annals.pdf

endocannabinoid endocannabinoid-mediated adiponectin obesity overweight weight-loss CB1

shared by Nathan Goodyear on 19 Mar 12 - No Cached
  • Nathan Goodyear on 19 Mar 12
     
    nice review of CB1 receptors and the role they play in obesity. Endocabbinoid receptors play an important role in the hypothalamus control of metabolism and energy. CB1 is active both centrally and peripherally. Increased CB1 activity increases fat storage; decrease CB1 activity increases fatty acid oxidation through adiponectin.
Nathan Goodyear

JAMA Network | JAMA: The Journal of the American Medical Association | Effects of Dietary Composition on Energy Expenditure During Weight-Loss MaintenanceDietary Composition During Weight-Loss Maintenance - 0 views

jama.jamanetwork.com/article.aspx

low carb low carbohydrate diet calories overweight obesity weight-loss energy

shared by Nathan Goodyear on 27 Jun 12 - No Cached
  • Nathan Goodyear on 27 Jun 12
     
    small study shows that low carb results in greater calories burned in weight loss.  The least calories burned goes to low fat diet.  Many, many studies have show the negative benefits of a low fat diet.
Nathan Goodyear

Testosterone and the brain. [Aging Male. 2006] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...17178554

testosterone therapy treatment low T low testosterone hypogonadal men mood depression hormone hormones brain male

shared by Nathan Goodyear on 06 Jul 12 - No Cached
  • Nathan Goodyear on 06 Jul 12
     
    testosterone therapy in men with "low T" will see improvement in mood i.e.. depression, energy...aggression associated with testosterone therapy is due to supra physiologic levels.
Nathan Goodyear

Neuron - Activation of Central Orexin/Hypocretin Neurons by Dietary Amino Acids - 0 views

www.cell.com/...S0896627311007823

amino acids fatigue afternoon sugar orexin_hpocretin cells

shared by Nathan Goodyear on 01 Dec 11 - No Cached
  • Nathan Goodyear on 01 Dec 11
     
    non-essential amino acids are beneficial in preventing those afternoon energy slumps.  Sugar with its resultant insulin spike would make this worse.
Nathan Goodyear

Gut flora and inflammation - 0 views

dl-web.dropbox.com/...obita%20and%20inflammation.pdf

gut flora microbiota inflammation obesity metabolic endotoxemia weight-loss overweight LPS

shared by Nathan Goodyear on 18 Jan 12 - No Cached
  • Nathan Goodyear on 18 Jan 12
     
    great review article of the current understanding on how the gut microbiota can influence energy homoestasis resulting in inflammation and obesity
Nathan Goodyear

Influence of high-carbohydrate mixed meals with different glycemic indexes on substrate utilization during subsequent exercise in women - 0 views

www.ajcn.org/...354.abstract

obesity overweight weight-loss low-glycemic exercise adipose fat

shared by Nathan Goodyear on 20 Dec 11 - No Cached
  • Nathan Goodyear on 20 Dec 11
     
    low-glycemic index diet aids in mobilization of adipose tissue in exercise.  In this study, exercise after a low-glycemic meal resulted in a greater mobilization of adipose tissue for energy production than a high glycemic meal.  This will help  in weight loss
Nathan Goodyear

Human gut microbiota in obesity and after gastric bypass - 0 views

dl-web.dropbox.com/...PNAS-2009-Zhang-0812600106.pdf

obesity weight loss inflammation metabolic endotoxemia bariatric surgery gastric bypass probiotics firmicutes gut flora microbiota

shared by Nathan Goodyear on 26 Jan 12 - No Cached
  • Nathan Goodyear on 26 Jan 12
     
    It is proposed that the balance of bacteria in the gut play a critical role in energy utilization and obesity. This study showed that bypass surgery altered the gut bacteria to favor weight loss: decrease in firmicutes species. But, do we really need gastric bypass to do that? Of course not. Probiotics will do the same.
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