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Nathan Goodyear

Lipoprotein(a) levels and long-term cardiovascular risk in the contemporary era of stat... - 0 views

www.ncbi.nlm.nih.gov/...PMC2936758

Lp(a) lipoprotein(a) cardiovascular disease risk heart health

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    Lp(a) found to highly correlate with obstructive coronary disease.
Nathan Goodyear

ScienceDirect - Clinical Biochemistry : Correlation between total homocysteine, low-den... - 0 views

www.sciencedirect.com/...S0009912001001874

homocysteine heart attack myocardial infarction

shared by Nathan Goodyear on 03 Aug 11 - No Cached
  • usefulness of LDL-C, HDL-C and serum total homocysteine as prognostic markers in myocardial infarction patients
  • Nathan Goodyear on 03 Aug 11
     
    homocysteine shown to be a good prognostic marker for patients with prior heart attacks
Nathan Goodyear

Testosterone level in men with type 2 diabetes mellitus and related metabolic... - 0 views

www.ncbi.nlm.nih.gov/...PMC4364844

low T low Testosterone Diabetes Testosterone men male hormones metabolic syndrome

shared by Nathan Goodyear on 30 Mar 15 - No Cached
  • defined by consistent symptoms and signs of androgen deficiency, and an unequivocally low serum testosterone level
  • the threshold serum testosterone level below which adverse clinical outcomes occur in the general population is not known
  • most population-based studies use the serum testosterone level corresponding to the lower limit, quoted from 8.7 to 12.7 nmol/L, of the normal range for young Caucasian men as the threshold
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      this equals 251 to 366 in serum Total Testosterone
  • ...57 more annotations...
  • Researchers tried to examine whether serum total or free testosterone would be a better/more reliable choice when studying the effect of testosterone. The results were mixed. Some reported significant associations of both serum total and free testosterone level with clinical parameters25, whereas others reported that only serum free testosterone26 or only serum total testosterone6 showed significant associations.
  • −0.124 nmol/L/year in serum total testosterone
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      this equates to a 4 ng/dl decline annually in total Testosterone.
  • In experimental studies, androgen receptor knockout mice developed significant insulin resistance rapidly
  • In mouse models, testosterone promoted differentiation of pluripotent stem cells to the myogenic lineage
  • testosterone decreased insulin resistance by enhancing catecholamine induced lipolysis in vitro, and reducing lipoprotein lipase activity and triglyceride uptake in human abdominal tissue in vivo
  • by promoting lipolysis and myogenesis, testosterone might lead to improved insulin resistance
  • testosterone regulated skeletal muscle genes involved in glucose metabolism that led to decreased systemic insulin resistance
  • In the liver, hepatic androgen receptor signaling inhibited development of insulin resistance in mice
  • independent and inverse association of testosterone with hepatic steatosis shown in a cross-sectional study carried out in humans
  • In short, androgen improves insulin resistance by changing body composition and reducing body fat.
  • Although a low serum testosterone level could contribute to the development of obesity and type 2 diabetes through changes in body composition, obesity might also alter the metabolism of testosterone
  • In obese men, the peripheral conversion from testosterone to estrogen could attenuate the amplitude of luteinizing hormone pulses and centrally inhibit testosterone production
  • leptin, an adipokine, has been shown to be inversely correlated with serum testosterone level in men
  • Leydig cells expressed leptin receptors and leptin has been shown to inhibit testosterone secretion, suggesting a role of obesity and leptin in the pathogenesis of low testosterone
    • Nathan Goodyear
      Nathan Goodyear on 31 Mar 15
       
      So what is "unequivocal"?
  • Baltimore Longitudinal Study of Aging (BLSA) cohort made up of 3,565 middle-class, mostly Caucasian men from the USA, the incidence of low serum total testosterone increased from approximately 20% of men aged over 60 years, 30% over 70 years, to 50% over 80 years-of-age
  • 30–44% sex hormone binding globulin (SHBG)-bound testosterone and 54–68% albumin-bound testosterone
  • As the binding of testosterone to albumin is non-specific and therefore not tight, the sum of free and albumin-bound testosterone is named bioavailable testosterone, which reflects the hormone available at the cellular level
  • Serum total testosterone is composed of 0.5–3.0% of free testosterone unbound to plasma proteins
  • alterations in SHBG concentration might affect total serum testosterone level without altering free or bioavailable testosterone
  • listed in Table​T
  • A significant, independent and longitudinal effect of age on testosterone has been observed with an average change of −0.124 nmol/L/year in serum total testosterone28. The same trend has been shown in Europe and Australia
  • Asian men residing in HK and Japan, but not those living in the USA, had 20% higher serum total testosterone than in Caucasians living in the USA, as shown in a large multinational observational prospective cohort of the Osteoporotic Fractures in Men Study
  • subjects with chronic diseases consistently had a 10–15% lower level compared with age-matched healthy subjects
  • In Caucasians, the mean serum total testosterone level for men in large epidemiological studies has been reported to range from 15.1 to 16.6 nmol/L
  • Asians, higher values, ranging from 18.1 to 19.1 nmol/L, were seen in Korea and Japan
  • Chinese middle-aged men reported a similar mean serum testosterone level of 17.1 nmol/L in 179 men who had a family history of type 2 diabetes and 17.8 nmol/L in 128 men who had no family history of type 2 diabetes
  • The reduction of total testosterone was 0.4% per year in both groups
  • HK involving a cohort of 1,489 community-dwelling men with a mean age of 72 years, a mean serum total testosterone of 19.0 nmol/L was reported
  • pro-inflammatory factors, such as tumor necrosis factor-α in the testes, could locally inhibit testosterone biosynthesis in Leydig cells47, and testosterone treatment in men was shown to reduce the level of tumor necrosis factor-α
  • In Asians, a genetic deletion polymorphism of uridine diphosphate-glucuronosyltransferase UGT2B17 was associated with reduced androgen glucuronidation. This resulted in higher level of active androgen in Asians as compared to Caucasians, as Caucasians' androgen would be glucuronidated into inactive forms faster.
  • Compared with Caucasians, the frequency of this deletion polymorphism of UGT2B17 was 22-fold higher in Asian subjects
  • Other researchers have suggested that environmental, but not genetic, factors influenced serum total testosterone
  • The basal and ligand-induced activity of the AR is inversely associated with the length of the CAG repeat chain
  • In the European Male Aging Study, increased estrogen/androgen ratio in association with longer AR CAG repeat was observed
  • a smaller number of AR CAG repeat had been shown to be associated with benign prostate hypertrophy and faster prostate growth during testosterone treatment
  • In India, men with CAG ≤19 had increased risk of prostate cancer
  • the odds of having a short CAG repeat (≤17) were substantially higher in patients with lymph node-positive prostate cancer than in those with lymph node-negative disease or in the general population
  • assessing the polymorphism at the AR level could be a potential tool towards individualized assessment and treatment of hypogonadism.
  • In elderly men, there was reduced testicular response to gonadotropins with suppressed and altered pulsatility of the hypothalamic pulse generator
  • a significant, independent and longitudinal effect of age on serum total testosterone level had been observed
  • A significant graded inverse association between serum testosterone level and insulin levels independent of age has also been reported in Caucasian men
  • Low testosterone is commonly associated with a high prevalence of MES
  • most studies showed that changes in serum testosterone level led to changes in body composition, insulin resistance and the presence of MES, the reverse might also be possible
  • MES predicted a 2.6-fold increased risk of development of low serum testosterone level independent of age, smoking and other potential confounders
  • Other prospective studies have shown that development of MES accelerated the age-related decline in serum testosterone level
  • In men with type 2 diabetes, changes in serum testosterone level over time correlated inversely with changes in insulin resistance
  • weight loss by either diet control or bariatric surgery led to a substantial increase in total testosterone, especially in morbidly obese men, and the rise in serum testosterone level was proportional to the amount of weight lost
  • To date, published clinical trials are small, of short duration and often used pharmacological, not physiological, doses of testosterone
  • In the population-based Osteoporotic Fractures in Men Study cohort from Sweden, men in the highest quartile of serum testosterone level had the lowest risk of cardiovascular events compared with men in the other three quartiles (hazard ratio [HR] 0.70
  • low serum total testosterone was associated with a significant fourfold higher risk of cardiovascular events when comparing men from the lowest testosterone tertile with those in the highest tertile
  • Shores et al. were the first to report that low serum testosterone level, including both serum total and free testosterone, was associated with increased mortality
  • low serum total testosterone predicted increased risk of cardiovascular mortality with a HR of 1.38
  • low serum total testosterone increased all-cause (HR 1.35, 95% CI 1.13–1.62, P < 0.001) and cardiovascular mortality (HR 1.25
  • European Association for the Study of Diabetes 2013 suggested there was an inverse relationship between serum testosterone level and acute myocardial infarction
  • Diabetic men in the highest quartile of serum total testosterone had a significantly reduced risk of acute MI when compared with those in the lower quartiles
  • serum total testosterone level in the middle two quartiles at baseline predicted reduced incidence of death compared with having the highest and lowest levels
  • Nathan Goodyear on 30 Mar 15
     
    Nice review of Testosterone levels and some of the evidence linking Diabetes with low T.  However, the conclusion by the authors regarding what is causing the low T in men with Diabetes is baffling.  The literature does not point to one cause, it is clearly multifactorial--obesity, inflammation, high aromatase activity...I would suggest the authors continue their readings in the manner.
Nathan Goodyear

Lowered testosterone in male obesity: Mechanisms, morbidity and management Tang Fui MN,... - 0 views

www.ajandrology.com/article.asp

Testosterone male obesity overweight men hormone hormones low T Low T

shared by Nathan Goodyear on 15 Jan 14 - No Cached
  • The number of overweight people is expected to increase from 937 million in 2005 to 1.35 billion in 2030
  • Similarly the number of obese people is projected to increase from 396 million in 2005 to 573 million in 2030
  • By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined
  • ...37 more annotations...
  • diacylglycerol O-acyltransferase 2 (DGAT2), mechanistically implicated in this differential storage, [10] is regulated by dihydrotestosterone, [11] suggesting a potential role for androgens to influence the genetic predisposition to either the MHO or MONW phenotype.
  • bariatric surgery achieves 10%-30% long-term weight loss in controlled studies
  • The fact that obese men have lower testosterone compared to lean men has been recognized for more than 30 years
  • Reductions in testosterone levels correlate with the severity of obesity and men
  • epidemiological data suggest that the single most powerful predictor of low testosterone is obesity, and that obesity is a major contributor of the age-associated decline in testosterone levels.
  • healthy ageing by itself is uncommonly associated with marked reductions in testosterone levels
  • obesity blunts this LH rise, obesity leads to hypothalamic-pituitary suppression irrespective of age which cannot be compensated for by physiological mechanisms
  • Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia
  • although controversial, measurement of free testosterone levels may provide a more accurate assessment of androgen status than the (usually preferred) measurement of total testosterone in situations where SHBG levels are outside the reference range
  • SHBG increases with age
  • marked obesity however is associated with an unequivocal reduction of free testosterone levels, where LH and follicle stimulating hormone (FSH) levels are usually low or inappropriately normal, suggesting that the dominant suppression occurs at the hypothalamic-pituitary level
  • adipose tissue, especially when in the inflamed, insulin-resistant state, expresses aromatase which converts testosterone to estradiol (E 2 ). Adipose E 2 in turn may feedback negatively to decrease pituitary gonadotropin secretion
  • diabetic obesity is associated with decreases in circulatory E 2
  • In addition to E 2 , increased visceral fat also releases increased amounts of pro-inflammatory cytokines, insulin and leptin; all of which may inhibit the activity of the HPT axis at multiple levels
  • In the prospective Massachusetts Male Aging Study (MMAS), moving from a non-obese to an obese state resulted in a decline of testosterone levels
  • weight loss, whether by diet or surgery, increases testosterone levels proportional to the amount of weight lost
  • fat is androgen-responsive
  • low testosterone may augment the effects of a hypercaloric diet
  • In human male ex vivo adipose tissue, testosterone decreased adipocyte differentiation by 50%.
  • Testosterone enhances catecholamine-induced lipolysis in vitro and reduces lipoprotein lipase activity and triglyceride uptake in human abdominal adipose tissue in vivo
  • in men with prostate cancer receiving 12 months of androgen deprivation therapy, fat mass increased by 3.4 kg and abdominal VAT by 22%, with the majority of these changes established within 6 months
  • severe sex steroid deficiency can increase fat mass rapidly
  • bidirectional relationship between testosterone and obesity
  • increasing body fat suppresses the HPT axis by multiple mechanisms [30] via increased secretion of pro-inflammatory cytokines, insulin resistance and diabetes; [19],[44] while on the other hand low testosterone promotes further accumulation of total and visceral fat mass, thereby exacerbating the gonadotropin inhibition
  • androgens may play a more significant role in VAT than SAT
  • men undergoing androgen depletion for prostate cancer show more marked increases in visceral compared to subcutaneous fat following treatment
    • Nathan Goodyear
      Nathan Goodyear on 16 Jan 14
       
      Interesting: low T increases VAT, yet T therapy does not reduce VAT, yet T therapy reduces SAT.
  • irisin, derived from muscle, induces brown fat-like properties in rodent white fat
  • androgens can act via the PPARg-pathway [37] which is implicated in the differentiation of precursor fat cells to the energy-consuming phenotype
  • low testosterone may compound the effect of increasing fat mass by making it more difficult for obese men to lose weight via exercise
  • pro-inflammatory cytokines released by adipose tissue may contribute to loss of muscle mass and function, leading to inactivity and further weight gain in a vicious cycle
  • Sarcopenic obesity, a phenotype recapitulated in men receiving ADT for prostate cancer, [55] may not only be associated with functional limitations, but also aggravate the metabolic risks of obesity;
  • observational evidence associating higher endogenous testosterone with reduced loss of muscle mass and crude measures of muscle function in men losing weight
  • genuine reactivation of the HPT axis in obese men requires more substantial weight-loss
  • A number of intervention studies have confirmed that both diet- and surgically-induced weight losses are associated with increased testosterone, with the rise in testosterone generally proportional to the amount of weight lost
  • men, regardless of obesity level, can benefit from the effect of weight loss.
  • inconsistent effect of testosterone on VAT
  • Nathan Goodyear on 15 Jan 14
     
    to be read
Nathan Goodyear

Endocrinology of the Aging Male - 0 views

www.ncbi.nlm.nih.gov/...PMC3073592

aging male hormone hormones

shared by Nathan Goodyear on 30 Apr 13 - No Cached
  • All steps beyond the formation of pregnenolone take place in the smooth endoplasmic reticulum
  • Cytochrome P450 enzyme, CYP11A is located on the inner mitochondrial membrane and catalyses the rate limiting step of pregnenolone synthesis
  • Estrogen and related steroids, thyroid hormone and insulin increase SHBG levels.
  • ...21 more annotations...
  • SHBG decreases in response to androgens, and in the presence of hypothyroidism, and insulin resistance.
  • Plasma SHBG levels tend to increase with increasing age
  • The apparent metabolic clearance rate of testosterone is decreased in elderly as compared to younger men
  • Testosterone circulates predominantly bound to the plasma proteins SHBG and albumin, with high and low affinity respectively
  • Testosterone is secreted in a pulsatile fashion
  • Current clinical guidelines suggest at least two measurements
  • In adult men, there is a well-documented diurnal variation (particularly in younger subjects) in testosterone levels, which are highest in the early morning and progressively decline throughout the day to a nadir in the evening
  • In older men, the diurnal variation is blunted
  • it is standard practice for samples to be obtained between 0800 and 1100 h.
  • Testosterone and DHEA decline, whereas LH, FSH, and SHBG rise
  • DHT remains constant despite the decline of its precursor testosterone
  • Longitudinal studies show an average annual decline of 1–2% total testosterone levels, with decline in free testosterone more rapid because of increases in SHBG with aging
  • Massachusetts Male Aging Study (MMAS) data show DHEA, DHEAS, and Ae declining at 2–3% per year
  • DHT showed no cross-sectional age trend
  • Androstanediol glucuronide (AAG) declined cross-sectionally with age in the MMAS sample, at 0.6% per year
  • The EMAS data show that, consistent with the longitudinal findings of MMAS (Figure 1), the core hormonal pattern with increasing age is suggestive of incipient primary testicular dysfunction with maintained total testosterone and progressively blunted free testosterone associated with higher LH
    • Nathan Goodyear
      Nathan Goodyear on 01 May 13
       
      This author proves the point in the review of these two studies, that TT may remain constant in aging men, however, FT drops.
  • obesity impairs hypothalamic/pituitary function
  • Androgen deprivation in men with prostate cancer has been associated with increased insulin resistance, worse glycemic control, and a significant increase in risk of incident diabetes
  • Low serum testosterone is associated with the development of metabolic syndrome 116, 117 and type 2 diabetes. 118 SHBG has been inversely correlated with type 2 diabetes
  • Improvement in insulin sensitivity with testosterone treatment has been reported in healthy 121 and diabetic 122 adult men
  • In studies conducted in men with central adiposity, testosterone has been shown to inhibit lipoprotein lipase activity in abdominal adipose tissue leading to decreased triglyceride uptake in central fat depots. 123
  • Nathan Goodyear on 30 Apr 13
     
    great review of hormone changes associated with aging in men.
Nathan Goodyear

Review of health risks of low testosterone and testosterone administration - 0 views

www.ncbi.nlm.nih.gov/...PMC4391003

low Testosterone low T Testosterone men male hormone hormones health

shared by Nathan Goodyear on 28 Apr 15 - No Cached
  • Hypogonadism may be defined either as serum concentration of T (either total T, bioavailable T or free T) or as low T plus symptoms of hypogonadism
  • The Baltimore Longitudinal Study on Aging reported the incidence of total serum T < 325 ng/dL to be 20% for men in their 60s, 30% for men in their 70s and 50% for men over 80
  • The Massachusetts Aging Male Study reported that 12.3% of men aged 40 to 70 had a total serum T of < 200 ng/dL with 3 or more symptoms of hypogonadism
  • ...19 more annotations...
  • The Boston Area Community Health Study reported that 5.6% of men aged 30 to 70 were hypogonadal, as defined by total serum T < 300 ng/dL; or, free serum T < 5 ng/dL plus 3 or more symptoms of hypogonadism
  • In a health screening project among 819 men in Taiwan, the prevalence of hypogonadism (total serum T < 300 ng/dL) ranged from 16.5% for men in their 40s, 23.0% for men in their 50s, 28.9% for men in their 60s, and 37.2% for men older than 70 years of age
  • The prevalence of hypogonadism among men in Taiwan is higher than the prevalence reported in the Massachusetts Male Aging Study
  • CAG repeat sequence, within the androgen receptor (AR). Rajender et al[12] reviewed over 30 studies on the AR trinucleotide repeat and infertility
  • suggestion that CAG repeat length may determine androgen responsiveness, this issue is not clearly settled
  • reported prevalence of low T in older men range from 5.6% to 50%
  • Those in the hypogonadal group (n = 4269) had direct health care costs, that exceeded the eugonadal group (n = 4269) by an average of $7100 over the course of the observation window
  • higher economic burden and presence of co-morbidities for hypogonadism
  • minor to moderate improvements in lean mass and muscle strength
  • increased bone mineral density
  • modest enhancement in sexual function
  • reduced adiposity
  • lessening of depressive symptoms
  • Meta-analyses of clinical TRT trials as of 2010 have identified three major adverse events resulting from TRT: (1) polycythemia; (2) an increase in prostate-related events; and (3) and a slight reduction in serum high-density lipoprotein (HDL) cholesterol
  • polycythemia (> 3.5-fold increase in risk
  • TRT produced a 40% prostate enlargement in older hypogonadal male Veterans over 12 mo
  • no published analysis has reported measurable increases in prostate cancer risk or Gleason score in men undergoing TRT, or in hypogonadal men with a history of prostate cancer undergoing TRT
  • the prostate which highly expresses the type II 5α-reductase enzyme. Inhibition of this enzyme via finasteride (a type II 5α-reductase inhibitor) or dutasteride (a dual type I and II 5α-reductase inhibitor) reduces circulating DHT 50%-75% and > 90%, respectively[47], and reduces prostate mass[48] and prostate cancer risk
  • Normally estradiol partially regulates testosterone levels, at the hypothalamus, blunting LH and FSH release from the pituitary. As a selective estrogen receptor modulator, CC interrupts this pathway, and consequently there is a greater stimulation for the production of testosterone in Leydig cells
    • Nathan Goodyear
      Nathan Goodyear on 28 Apr 15
       
      this would only apply if E1 and/or E2 levels were elevated, which the authors make no mention of.
  • Nathan Goodyear on 28 Apr 15
     
    to be read
Nathan Goodyear

Cross-kingdom inhibition of breast cancer growth by plant miR159 - 0 views

www.ncbi.nlm.nih.gov/...PMC4746606

cancer epigenetics nutrigenomics nutrition diet

shared by Nathan Goodyear on 11 Dec 17 - No Cached
  • MicroRNAs (miRNAs), a major family of small RNAs, are ∼23 nt-long single strands of RNA that bind to mRNA transcripts to inhibit their translation
  • A recent study by Zhang et al. reported that plant-derived miRNAs can be found in human serum.
  • The group demonstrates that the plant miRNA miR168 may be taken up through dietary intake to inhibit the expression of its target low-density lipoprotein receptor 1 in the liver21, providing the first evidence that miRNA in food may influence gene expression in mammalian organs.
  • ...6 more annotations...
  • A more recent finding by the same group shows that a plant miRNA from honeysuckle is able to inhibit Influenza A replication22, indicating that plant miRNAs may be useful for treating human diseases.
  • We found that plant miR159 could be detected in human sera and its levels were inversely correlated with BC incidence and progression.
  • We further identified TCF7 as a mammalian target for miR159 and showed the anti-proliferative function of miR159 in BC cells using in vitro and in vivo models, demonstrating for the first time that a plant miRNA is able to influence BC cell growth.
  • certain dietary miRNAs from plants and other species may serve as highly affordable and powerful means of treatment with minimal inconvenience to patients.
  • miR159 which (using a synthetic mimic) targets TCF7 to inhibit the proliferation of cells whose growth is dependent on TCF7 such as the BC cells MDA-MB-231
  • our study using a BC model clearly indicates the anti-tumor effect of orally administered synthetic miR159 in its naturally existing form with the plant-specific 2'-O-methylation, suggesting the feasibility of using synthetic forms of plant miRNAs as dietary supplements in the treatment of human cancers, including those outside of the GI track
  • Nathan Goodyear on 11 Dec 17
     
    Plant microRNA found to exist in human serum from gut absorption to then alter genetic expression in in-vitro and in vivo studies.
Nathan Goodyear

Apo B/Apo A-I Ratio is Statistically A Better Predictor of Cardiovascular Disease (CVD)... - 0 views

www.ncbi.nlm.nih.gov/...PMC3972591

cardiovascular disease Apo B:Apo A1 cholesterol apo A1 apo B apolipoprotein lipoprotein Apolipoprotein B Apolipoprotien A1 risk

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    Apo B:apo A1 is a better predictor of cardiovascular risk than a traditional cholesterol panel is.
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

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

Redefining Metabolic Syndrome in Men (July 2012) Townsend Letter for Doctors & Patients - 0 views

www.townsendletter.com/...metsyndrome0712.html

testosterone male men hormone hormones saliva salivary low T low metabolic syndrome MetS

shared by Nathan Goodyear on 28 Aug 12 - No Cached
  • Approximately 95% to 98% of testosterone is bound to a carrier protein at any given time, leaving just the remaining 2% to 5% as completely unbound and available for tissues to use
  • most serum laboratories offer a free testosterone level, which is a calculated value based on SHBG levels or determined with equilibrium dialysis
  • the hormone enters the salivary gland by passive diffusion
  • ...11 more annotations...
  • Testosterone has a known age-related decline, and total levels typically drop by approximately 1.6% per year beginning for most men in their 30s
  • As estrogen levels rise, they prompt the body to produce more SHBG, which in turn has a higher binding affinity for testosterone, and drives the unbound fraction of the testosterone pool down even further
  • When the increase in SHBG is taken into account, the age-related decline in the level of hormone that can be used by the body is closer to 2% to 3% per year.
  • Stinging nettle (Urtica dioica), an herb commonly used for allergies, can also be employed to bind to SHBG, which leaves more testosterone available to tissues
  • Leptin, an adipose-derived peptide hormone that regulates appetite and metabolism, has been shown to directly inhibit testosterone production in animal models
  • tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) further inhibit Leydig cell testosterone production
  • Natural aromatase inhibitors include the bioflavonoids chrysin and luteolin
  • Zinc deficiency causes an upregulation of the aromatase enzyme
  • Testosterone reduces lipoprotein lipase (LPL) activity
  • there are several herbs that can work to boost testosterone levels, including longjack (Eurycoma longifolia), horny goat weed (Epimedium grandiflorum), and tribulus (Tribulus terrestris).
  • the majority of the hormone is bound to carrier proteins including sex hormone binding globulin (SHBG) and albumin
  • Nathan Goodyear on 28 Aug 12
     
    nice and short review on testosterone and men's  health.
Nathan Goodyear

http://eurheartj.oxfordjournals.org/content/26/16/1633.full.pdf - 0 views

eurheartj.oxfordjournals.org/...1633.full.pdf

Lp(a) lipoprotein(a) cardiovascular disease risk heart health

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    Lp(a) associated with increased risk at levels > 30 in women.  The risk is double.
Nathan Goodyear

High apolipoprotein B, low apolipoprotein A-I, and improvement in the prediction of fat... - 0 views

www.thelancet.com/...fulltext

lipoproteins apolipoproteins apo B apo A1 Apo B:Apo A1 Apolipoprotein B Apolipoprotien A1 cholesterol heart health cardiovascular disease risk

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    Study finds strong correlation between Apo B and Apo B:apo A1 in fatal MI risk in men and women.  Apo B was a stronger than LDL in predicting risk in men and women.  Apo A1 was noted to be protective, but the stats were less strong.
Nathan Goodyear

International Journal of Impotence Research - Obesity, low testosterone levels and erec... - 0 views

www.nature.com/...ijir200842a.html

low T low Testosterone men male hormone hormones ED erectile dysfunction Testosterone diabetes metabolic syndrome obesity

shared by Nathan Goodyear on 27 Jan 15 - No Cached
  • Studies have shown that ED may be an early biomarker of general endothelial dysfunction, atherosclerosis and CVD
  • testosterone treatment of hypogonadal young and older men improves sexual function, increases lean mass and decreases fat mass
  • In men with low serum testosterone (for example, <8 or 230 nmol l−1) with obesity, metabolic syndrome and diabetes mellitus, treatment with testosterone is warranted
  • ...12 more annotations...
  • In obese middle-aged men, testosterone treatment reduced visceral adipocity, insulin resistance, serum cholesterol and glucose levels
  • testosterone replacement has a favorable impact on body mass, insulin secretion and sensitivity, lipid profile and blood pressure in hypogonadal men with the metabolic syndrome as well as type 2 diabetes mellitus
  • Testosterone significantly inhibits lipoprotein lipase activity, which reduces triglycerides uptake into adipocytes in the abdominal adipose tissue
  • testosterone treatment decreased endogenous inflammatory cytokines (tumor necrosis factor-α and IL-1β) and lipids (total cholesterol) and increased IL-10 in hypogonadal men
  • Testosterone treatment reduced leptin and adiponectin levels in hypogonadal type 2 diabetic men after 3 months of testosterone replacement
  • available data clearly show a relationship between obesity, low testosterone levels and ED
  • Obesity adversely affects endothelial function and lowers serum testosterone levels through the development of insulin resistance and metabolic syndrome
  • Metabolic disturbances as well as production of cytokines and adipokines by inflamed fat cells may be causal factors in the development of ED
  • The onset of ED and the associated risk of CVD may be delayed through lifestyle modifications that affect obesity, such as diet and exercise
  • Very low testosterone levels contribute to the development of ED in obesity, metabolic syndrome and type 2 diabetes mellitus
  • Obesity is associated with low total testosterone levels that can be explained at least partially by lower sex hormone-binding globulin (SHBG) in obese men
  • epidemiological studies have shown a negative correlation between BMI and total testosterone and to a lesser extent with free and bioavailable (biologically active) testosterone levels
  • Nathan Goodyear on 27 Jan 15
     
    Obesity is associated with low Testosterone and ED in men.
Nathan Goodyear

Ozone therapy: A clinical review - 0 views

www.ncbi.nlm.nih.gov/...PMC3312702

cancer Ozone

shared by Nathan Goodyear on 13 Apr 20 - No Cached
  • Its basic function is to protect humans from harmful effects of UV radiation
  • Its effects are proven, consistent and with minimal side effects
  • Medical O3, used to disinfect and treat disease, has been around for over 150 years
  • ...11 more annotations...
  • O3 not only remedied infection, but also had hemodynamic and anti-inflammatory properties
  • Stimulation of oxygen metabolism
  • In fungi, O3 inhibits cell growth at certain stages
  • With viruses, the O3 damages the viral capsid and upsets the reproductive cycle by disrupting the virus-to-cell contact with peroxidation.
  • Inactivation of bacteria, viruses, fungi, yeast and protozoa: Ozone therapy disrupts the integrity of the bacterial cell envelope through oxidation of the phospholipids and lipoproteins
  • Activation of the immune system
  • 30 and 55 μg/cc
  • production of interferon and the greatest output of tumor necrosis factor and interleukin-2
  • Mechanism of action of O3 on the human lung
  • cascade of reactions like peroxidation of lipids leading to changes in membrane permeability,[41] lipid ozonation products (LOP) act as signal transducer molecules
  • Dietary antioxidants or free radical scavengers like vitamin E, C, etc., can prevent aforementioned effects of O3
  • Nathan Goodyear on 13 Apr 20
     
    Ozone therapy review
Nathan Goodyear

Effects of exogenous ketone supplementation on blood ketone, glucose, triglyceride, and... - 0 views

www.ncbi.nlm.nih.gov/...PMC4743170

ketones ketone bodies ketone salts BHB Beta-hydroxybutyrate MCT MCTs medium chain triglycerides

shared by Nathan Goodyear on 21 Nov 16 - No Cached
  • Nathan Goodyear on 21 Nov 16
     
    animal study finds increased BHB after ketone salt supplementation.  A resultant decrease in glucose was found.  The use of ketone salts was with concomitant MCT.  The effect was in 30-60 minutes and sustained, significantly for 8 hours.  Weight loss was also seen.  No change in cholesterol and triglycerides was seen.
Nathan Goodyear

Apolipoproteins versus lipids as indices of coronary risk and as targets for statin tre... - 0 views

www.thelancet.com/...fulltext

lipoproteins Apolipoprotein B apo B CVD cardiovascular disease risk heart health

shared by Nathan Goodyear on 26 Aug 14 - No Cached
  • Nathan Goodyear on 26 Aug 14
     
    apo B is a surrogate marker for LDL particle #.  However, it is an independent risk biomarker itself.
Nathan Goodyear

Apolipoprotein B and Cardiovascular Disease Risk: Position Statement from the AACC Lipo... - 0 views

clinchem.aaccjnls.org/...407

apo B Apolipoprotein B cardiovascular disease LDL cholesterol

shared by Nathan Goodyear on 13 Dec 17 - No Cached
  • Nathan Goodyear on 13 Dec 17
     
    ApoB is a better measure of risk than LDL.
Nathan Goodyear

Association Between Low-Density Lipoprotein Cholesterol-Lowering Genetic Variants and R... - 0 views

www.ncbi.nlm.nih.gov/...27701660

statins diabetes LDL

shared by Nathan Goodyear on 27 Oct 16 - No Cached
  • Nathan Goodyear on 27 Oct 16
     
    statins associated with increase risk of type II diabetes for some with genetic variants.
Nathan Goodyear

Lack of an association or an inverse association between low-density-lipoprotein choles... - 0 views

bmjopen.bmj.com/...e010401.full

LDL cholesterol mortality elderly

shared by Nathan Goodyear on 14 Jun 16 - No Cached
  • Nathan Goodyear on 14 Jun 16
     
    review study of 263 studies finds no association between LDL and mortality in elderly.  In fact, the review found an inverse association between LDL and mortality i.e. increasing LDL associated with lower mortality in elderly.
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