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Nathan Goodyear

Metabolic syndrome as a prognostic factor for breast cancer recurrences - Pasanisi - 20... - 0 views

onlinelibrary.wiley.com/...full

Testosterone women metabolic syndrome metabolic syndrome breast cancer

shared by Nathan Goodyear on 12 Mar 14 - No Cached
  • Nathan Goodyear on 12 Mar 14
     
    Women with metabolic syndrome have increased recurrence of breast cancer after initial therapy.  Likewise, Increasing Testosterone was associated with increasing risk of metabolic syndrome.  This is the opposite of men.  One wonders what this massive doping of Testosterone that is underway is doing to women?  Are we merely feeding disease?
Nathan Goodyear

Uric Acid Stimulates Fructokinase and Accelerates Fructose Metabolism in the Developmen... - 0 views

www.ncbi.nlm.nih.gov/...PMC3480441

non-alcoholic fatty liver fatty liver fructose uric acid

shared by Nathan Goodyear on 01 Oct 13 - No Cached
  • Nathan Goodyear on 01 Oct 13
     
    Vicious cycle.  High fructose intake increases uric acid production.  Hyperuricemia then leads to further Fructose metabolism.  This study finds that hyperuricemia upregulates the fructokinase enzyme that is the first step in fructose metabolism.  This upregulation will increase fructose metabolism and increase fat accumulation in the liver.
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

Early Life Exposure to Fructose and Offspring Phenotype: Implications for Long Term Met... - 0 views

www.hindawi.com/...203474

fructose metabolism metabolic dysfunction

shared by Nathan Goodyear on 28 May 14 - No Cached
  • Nathan Goodyear on 28 May 14
     
    High fructose intake has negative metabolic effects in the mother and the child.  This leads the child down the path of metabolic dysfunction that will result in disease.
Nathan Goodyear

http://www.farm.ucl.ac.be/Full-texts-FARM/Delzenne-2010-3.pdf - 0 views

www.farm.ucl.ac.be/...Delzenne-2010-3.pdf

metabolic endotoxemia metabolic syndrome metabolic syndrome inflammation probiotics probiotic prebiotics prebiotic

shared by Nathan Goodyear on 11 Sep 14 - No Cached
  • Nathan Goodyear on 11 Sep 14
     
    Good review of metabolic endotoxemia, inflammation, and the use of probiotics, prebiotics to reduce inflammation and effect energy balance.  Implications in metabolic syndrome.
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

Estradiol and Metabolic Syndrome in Older Italian Men: the InCHIANTI Study - 0 views

www.ncbi.nlm.nih.gov/...PMC2842460

Men hormone hormones estradiol estrogen metabolic syndrome MetS InCHIANTI study

shared by Nathan Goodyear on 30 Apr 13 - No Cached
  • Nathan Goodyear on 30 Apr 13
     
    Men with metabolic syndrome found to be associated with higher Estradiol levels.  Thus, Estradiol in "older men", >65 in this study, is associated with metabolic syndrome.
Nathan Goodyear

Urolithiasis is associated with low serum testosterone levels in men | Otunctemur | Arc... - 0 views

www.pagepressjournals.org/...4580

urolithiasis kidney stones low T low Testosterone men male hormone hormones metabolic syndrome

shared by Nathan Goodyear on 13 Apr 15 - No Cached
  • Nathan Goodyear on 13 Apr 15
     
    low Testosterone is associated with kidney stones in men through increased Metabolic Syndrome.  Better stated, low T is associated with metabolic syndrome and this metabolic dysfunction increased the findings of kidney stones in men.
Nathan Goodyear

Effects of Testosterone Replacement on Metabolic and Inflammatory Markers in Men with O... - 0 views

www.ncbi.nlm.nih.gov/...26928845

low T low Testosterone Testosterone opiates men male hormones inflammation

shared by Nathan Goodyear on 02 Mar 16 - No Cached
  • Nathan Goodyear on 02 Mar 16
     
    Opiates and prescription meds are a common cause of low T in men.  In this study with men with metabolic dysfunction and opiate induced low T, Testosterone therapy did not worsen inflammatory/metabolic markers.  Of note, this study did not find improvement in the metabolic and inflammatory markers as other studies have shown.
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

ScienceDirect.com - The Journal of Nutritional Biochemistry - The role of dietary fatty... - 0 views

www.sciencedirect.com/...S0955286312000605

metabolic syndrome dietary fatty acids nutritional biochemistry

shared by Nathan Goodyear on 24 Sep 12 - No Cached
  • Nathan Goodyear on 24 Sep 12
     
    disordered fat metabolism plays a role in metabolic syndrome
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

Beyond the male sex hormone: deciphering the metabolic and vascular actions of testoste... - 0 views

joe.endocrinology-journals.org/...C1.full

AR androgen receptors androgen receptor testosterone androgen receptors Diabetes metabolic syndrome MetS CVD cardiovascular disease men hormone hormones male

shared by Nathan Goodyear on 08 May 13 - No Cached
  • androgen deprivation therapy results in unfavorable changes in body composition, insulin resistance, and dyslipidemia and predisposes men to develop atherosclerosis and an increased risk of cardiovascular mortality
  • The hypogonadal–obesity cycle hypothesis was originally proposed by Cohen in 1999 to explain the relationship between low testosterone levels and metabolic disease. It was based on the finding that obesity impairs testosterone levels by increasing the aromatization of testosterone to estradiol, while low testosterone levels promote increased fat deposition
  • adipocytokines contribute to low testosterone levels as well as to the processes underlying metabolic syndromes and type 2 diabetes
  • ...15 more annotations...
  • hypogonadal–obesity–adipocytokine hypothesis
  • The presence of estradiol and the adipocytokines TNF-α, IL6, and leptin (as a result of leptin resistance in obesity) inhibits the hypothalamic–pituitary–testicular axis response to decreasing androgen levels
  • An increasing number of studies have illustrated the potential for applying metabolomics to the field of androgen research
  • As early as the 1940s, the therapeutic use of testosterone was reported to improve angina pectoris in men with coronary artery disease
  • most of the epidemiological studies reported increased cardiovascular risk and mortality in men with low testosterone levels
  • long-term testosterone replacement appears to be a safe and effective means of treating hypogonadal elderly men
  • a recent interventional trial showed that testosterone treatment was associated with decreased mortality when compared with no testosterone treatment in an observational cohort of men with low testosterone levels
  • a number of short-term studies conducted support the notion that testosterone therapy reduces the cardiovascular risk
  • The majority of animal studies support the hypothesis that the actions of testosterone on vascular relaxation are both endothelium-dependent and -independent vasodilatory effects
  • Endothelial-dependent actions of testosterone increase the expression or activity of endothelial nitric oxide synthase and enhance nitric oxide production, which in turn activates cyclic guanosine monophosphate to induce vasorelaxation in smooth muscle cells
  • Endothelial-independent mechanisms of testosterone are believed to occur primarily via inhibition of voltage-operated Ca2+ channels and/or activation of K+ channels in smooth muscle cells
  • Testosterone may also inhibit intracellular Ca2+ influx via store-operated Ca2+ channels by blocking the response to prostaglandin F2α
  • testosterone has demonstrated anti-inflammatory effects to protect against atherogenesis in animal studies
  • both genomic AR activation to modulate gene transcription and non-genomic activation to modulate the rapid intracellular signaling pathways of ion channels may mediate testosterone effects on vascular function and inflammation.
  • Butenandt & Ruzicka first showed how testosterone is synthesized and responsible for masculine characteristics in the early 1930s
  • Nathan Goodyear on 08 May 13
     
    Awesome review on the current understanding of Testosterone and Diabetes, metabolic syndrome, and CVD.  This article even goes into the literature on androgen receptors.
Nathan Goodyear

Genetic Analysis of 16 NMR-Lipoprotein Fractions in H... [Lipids. 2012] - PubMed - NCBI - 0 views

www.ncbi.nlm.nih.gov/...23192668

SNPs single nucleotide polymorphisms genes genetics lipid metabolism metabolism weight overweight obesity

shared by Nathan Goodyear on 24 Jan 13 - No Cached
  • Nathan Goodyear on 24 Jan 13
     
    genetic SNPs play a role in lipid/fat metabolism. A person's weight problem may be, in part, a genetic problem of fat metabolism.
Nathan Goodyear

Testosterone and insulin resistance in the metabolic syndrome and T2DM in men : Abstrac... - 0 views

www.nature.com/...nrendo.2013.122.html

low T low testosterone testosterone oxidative phosphorylation insulin resistance insulin resistance metabolic syndrome

shared by Nathan Goodyear on 02 Jul 13 - No Cached
  • Nathan Goodyear on 02 Jul 13
     
    low Testosterone in men negatively impacts insulin sensitivity, glucose metabolism and oxidative phosphorylation resulting in physical manifest ions found in metabolic syndrome.
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 Initiates Obesity and Insulin Resistance - 0 views

diabetes.diabetesjournals.org/...1761.long

metabolic endotoxemia obesity insulin resistance

shared by Nathan Goodyear on 05 Sep 12 - No Cached
  • Nathan Goodyear on 05 Sep 12
     
    metabolic endotoxemia and obesity and insulin resistance.  This article suggests that metabolic endotoxemia initiates the development.
Nathan Goodyear

BMC Public Health | Abstract | High prevalence of vitamin D insufficiency and its assoc... - 0 views

www.biomedcentral.com/...abstract

vitamin-D D D3 obesity weight-loss metabolic syndrome vitamin overweight

shared by Nathan Goodyear on 08 Dec 11 - No Cached
  • Nathan Goodyear on 08 Dec 11
     
    Malaysians with metabolic syndrome and obesity found to have high prevalence of vitamin D insufficiency.  Role for vitamin D therapy for those with metabolic syndrome and obesity.
Nathan Goodyear

JCI - Inflammatory links between obesity and metabolic disease - 0 views

www.jci.org/57132

obesity overweight weight-loss inflammation metabolic disease

shared by Nathan Goodyear on 04 Jan 12 - No Cached
  • metainflammation
  • The chronic nature of obesity produces a tonic low-grade activation of the innate immune system that affects steady-state measures of metabolic homeostasis over time
  • It is clear that inflammation participates in the link between obesity and disease
  • ...25 more annotations...
  • Multiple inflammatory inputs contribute to metabolic dysfunction, including increases in circulating cytokines (10), decreases in protective factors (e.g., adiponectin; ref. 11), and communication between inflammatory and metabolic cells
  • adipose tissue macrophage (ATM)
  • Physiologic enhancement of the M2 pathways (e.g., eosinophil recruitment in parasitic infection) also appears to be capable of reducing metainflammation and improving insulin sensitivity (27).
  • increasing adiposity results in a shift in the inflammatory profile of ATMs as a whole from an M2 state to one in which classical M1 proinflammatory signals predominate (21–23).
  • The M2 activation state is intrinsically linked to the activity of PPARδ and PPARγ
  • well-known regulators of lipid metabolism and mitochondrial activity
  • Independent of obesity, hypothalamic inflammation can impair insulin release from β cells, impair peripheral insulin action, and potentiate hypertension (63–65).
  • inflammation in pancreatic islets can reduce insulin secretion and trigger β cell apoptosis leading to decreased islet mass, critical events in the progression to diabetes (33, 34)
  • Since an estimated excess of 20–30 million macrophages accumulate with each kilogram of excess fat in humans, one could argue that increased adipose tissue mass is de facto a state of increased inflammatory mass
  • JNK, TLR4, ER stress)
  • NAFLD is associated with an increase in M1/Th1 cytokines and quantitative increases in immune cells
  • Upon stimulation by LPS and IFN-γ, macrophages assume a classical proinflammatory activation state (M1) that generates bactericidal or Th1 responses typically associated with obesity
  • DIO, metabolites such as diacylglycerols and ceramides accumulate in the hypothalamus and induce leptin and insulin resistance in the CNS (58, 59)
  • saturated FAs, which activate neuronal JNK and NF-κB signaling pathways with direct effects on leptin and insulin signaling (60)
  • Lipid infusion and a high-fat diet (HFD) activate hypothalamic inflammatory signaling pathways, resulting in increased food intake and nutrient storage (57)
  • Maternal obesity is associated with endotoxemia and ATM accumulation that may affect the developing fetus (73)
  • Placental inflammation is a characteristic of maternal obesity
  • a risk factor for obesity in offspring, and involves inflammatory macrophage infiltration that can alter the maternal-fetal circulation (74
  • Of these PRRs, TLR4 has received the most attention, as this receptor can be activated by free FAs to generate proinflammatory signals and activate NF-κB
  • Nod-like receptor (NLR) family of PRRs
  • ceramides and sphingolipids
  • The adipokine adiponectin has long been recognized to have positive benefits on multiple cell types to promote insulin sensitivity and deactivate proinflammatory pathways.
  • adiponectin stimulates ceramidase activity and modulates the balance between ceramides and sphingosine-1-phosphate
  • Inhibition of ceramide production blocks the ability of saturated FAs to induce insulin resistance (101)
  • NF-κB, obesity also activates JNK in insulin-responsive tissues
  • Nathan Goodyear on 04 Jan 12
     
    must read to see our current knowledge on the link between inflammation and obesity.
Nathan Goodyear

Testosterone and glucose metabolism in men: current concepts and controversies - 0 views

joe.endocrinology-journals.org/...R37.full

shared by Nathan Goodyear on 04 Feb 14 - No Cached
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      80% of E2 production in men, that will cause low T in men, comes from SQ adiposity.  This leads to increase in visceral adiposity.
  • Only 5% of men with type 2 diabetes have elevated LH levels (Dhindsa et al. 2004, 2011). This is consistent with recent findings that the inhibition of the gonadal axis predominantly takes place in the hypothalamus, especially with more severe obesity
  • Metabolic factors, such as leptin, insulin (via deficiency or resistance) and ghrelin are believed to act at the ventromedial and arcuate nuclei of the hypothalamus to inhibit gonadotropin-releasing hormone (GNRH) secretion
  • ...32 more annotations...
  • kisspeptin has emerged as one of the most potent secretagogues of GNRH release
  • Consistent with the hypothesis that obesity-mediated inhibition of kisspeptin signalling contributes to the suppression of the HPT axis, infusion of a bioactive kisspeptin fragment has been recently shown to robustly increase LH pulsatility, LH levels and circulating testosterone in hypotestosteronaemic men with type 2 diabetes
  • Figure 4
  • Interestingly, a recent 16-week study of experimentally induced hypogonadism in healthy men with graded testosterone add-back either with or without concomitant aromatase inhibitor treatment has in fact suggested that low oestradiol (but not low testosterone) may be responsible for the hypogonadism-associated increase in total body and intra-abdominal fat mass
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      This does not fit with the research on receptors, specifically estrogen receptors.  These studies that the authors are referencing are looking at "circulating" levels, not tissue levels.
  • A smaller study with a similar experimental design found that acute testosterone withdrawal reduced insulin sensitivity independent of body weight, whereas oestradiol withdrawal had no effects
  • Obesity and dysglycaemia and associated comorbidities such as obstructive sleep apnoea (Hoyos et al. 2012b) are important contributors to the suppression of the HPT axis
  • This is supported by observational studies showing that weight gain and development of diabetes accelerate the age-related decline in testosterone
  • Weight loss can reactivate the hypothalamic–pituitary–testicular axis
  • The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
  • Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
  • Several observational and randomised studies reviewed in Grossmann (2011) have shown that weight loss, whether by diet or surgery, leads to substantial increases in testosterone, especially in morbidly obese men
  • This suggests that weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
  • There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
  • in those men in whom glycaemic control worsened, testosterone decreased
  • successful weight loss combined with optimisation of glycaemic control may be sufficient to normalise circulating testosterone levels in the majority of such men
  • weight loss, optimisation of diabetic control and assiduous care of comorbidities should remain the first-line approach.
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      This obviously goes against marketing-based medicine
  • In part, the discrepant results may be due to the fact men in the Vigen cohort (Vigen et al. 2013) had a higher burden of comorbidities. Given that one (Basaria et al. 2010), but not all (Srinivas-Shankar et al. 2010), RCTs in men with a similarly high burden of comorbidities reported an increase in cardiovascular events in men randomised to testosterone treatment (see section on Testosterone therapy: potential risks below) (Basaria et al. 2010), testosterone should be used with caution in frail men with multiple comorbidities
  • The retrospective, non-randomised and non-blinded design of these studies (Shores et al. 2012, Muraleedharan et al. 2013, Vigen et al. 2013) leaves open the possibility for residual confounding and multiple other sources of bias. These have been elegantly summarised by Wu (2012).
  • Effects of testosterone therapy on body composition were metabolically favourable with modest decreases in fat mass and increases in lean body mass
  • This suggests that testosterone has limited effects on glucose metabolism in relatively healthy men with only mildly reduced testosterone.
  • it is conceivable that testosterone treatment may have more significant effects on glucose metabolism in uncontrolled diabetes, akin to what has generally been shown for conventional anti-diabetic medications.
  • the evidence from controlled studies show that testosterone therapy consistently reduces fat mass and increases lean body mass, but inconsistently decreases insulin resistance.
  • Interestingly, testosterone therapy does not consistently improve glucose metabolism despite a reduction in fat mass and an increase in lean mass
  • the majority of RCTs (recently reviewed in Ng Tang Fui et al. (2013a)) showed that testosterone therapy does not reduce visceral fat
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      visceral and abdominal adiposity are biologically different and thus the risks associated with the two are different.
    • Nathan Goodyear
      Nathan Goodyear on 04 Feb 14
       
      yet low T is associated with an increase in visceral adiposity--confusing!
  • testosterone therapy decreases SHBG
  • testosterone is inversely associated with total cholesterol, LDL cholesterol and triglyceride (Tg) levels, but positively associated with HDL cholesterol levels, even if adjusted for confounders
  • Although observational studies show a consistent association of low testosterone with adverse lipid profiles, whether testosterone therapy exerts beneficial effects on lipid profiles is less clear
  • Whereas testosterone-induced decreases in total cholesterol, LDL cholesterol and Lpa are expected to reduce cardiovascular risk, testosterone also decreases the levels of the cardio-protective HDL cholesterol. Therefore, the net effect of testosterone therapy on cardiovascular risk remains uncertain.
  • data have not shown evidence that testosterone causes prostate cancer, or that it makes subclinical prostate cancer grow
  • compared with otherwise healthy young men with organic androgen deficiency, there may be increased risks in older, obese men because of comorbidities and of decreased testosterone clearance
  • recent evidence that fat accumulation may be oestradiol-, rather than testosterone-dependent
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