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Nathan Goodyear

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

  • 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)
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  • 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
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    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

Moderate protein intake improves total and region... [Metabolism. 2008] - PubMed - NCBI - 0 views

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    moderate protein intake defined here as 25%.  The physiologic effects of moderate protein intake the same as high protein intake--40%.  This study finds an improvement in insulin senstivity in the short term.  
Nathan Goodyear

http://jap.physiology.org/content/jap/82/1/49.full.pdf - 0 views

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    To much protein intake can be a bad thing.  This study found that high protein intake and high protein/carbohydrate intake lowered basal Testosterone levels.
Nathan Goodyear

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

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    high caffeine intake found to be associated with increased Testosterone and cortisol pre and post resistance work out times.  An elevated Testosterone would be good at both points.  However, an elevated cortisol would be catabolic during the recovery phase.  The study also found a decrease in insulin sensitivity with high caffeine intake.  This was improved with moderate and low intake.
Nathan Goodyear

ScienceDirect.com - Physiology & Behavior - Effects of leptin and orexin-A on food inta... - 0 views

  • orexin-A and orexin-B, localized in the posterior and lateral hypothalamic perifornical region were discovered in the rat brain and they increase food intake
  • Leptin, a protein encoded by an obesity gene, expressed in adipose tissue and released into the blood also affects food intake
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    Leptin and orexins regulate appetite regulate food intake.
Nathan Goodyear

Altered Preconception Fatty Acid Intake Is Associated with Improved Pregnancy Rates in ... - 0 views

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    Health fat intake associated with improved fertility in overweight and obese women undergoing IVF.  Higher intake of polyunsaturated fats were associated with improved fertile rates: specifically omega 6 and Linoleum acid.  Only a trend was seen with omega 3's.
Nathan Goodyear

Interaction between a peroxisome proliferator-activated receptor γ gene polym... - 0 views

  • uniform dietary recommendations may not be appropriate for all individuals
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    Peroxisome proliferator-activated receptor gamma plays an important role in obesity and fat generation.  In this study, they showed how the genetic expression of different PPAR gamma genotypes results in altered physiologic response to fat intake in humans.  The interaction between genetics and the environment.
Nathan Goodyear

Diet and Sex Hormone-Binding Globulin - 0 views

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    In men, flax intake is positively associated with SHBG; whereas protein intake is inversely associated with SHBG.
Nathan Goodyear

Divergent trends in obesity and fat intake patterns... [Am J Med. 1997] - PubMed - NCBI - 0 views

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    Fat intake is inversely associated with the obesity trend.  During, the 80's, a low fat diet was all the craze.  However, the obesity trend increased with the incorporation of the the low fat diet in America.
Nathan Goodyear

Relation between consumption of sugar-sweetened drinks and childhood obesity: a prospec... - 0 views

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    soda intake is associated with increased BMI. Take home, the more soda intake, the higher the obesity. This study looked at children.
Nathan Goodyear

The role of long chain fatty acids in regulating food intake and cholecystokinin releas... - 0 views

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    long chain fatty acids (LCFA), associated with decreased calorie intake.  This occurs through up regulation/release of cholecystokinin.
Nathan Goodyear

Vitamin C and survival among women with breast cancer: A Meta-analysis - 0 views

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    Meta-analysis finds that for every oral daily intake of 100 mg vitamin C, the risk of total mortality was decreased by 27% and the breast cancer specific mortality was decreased by 22%.  A lot of potential variables that can play into this equation.  However, oral vitamin C is poorly bioavailable, yet according to this meta-analysis, does provide significant health benefits and even prevention.  If health and breast cancer prevention is a goal, then vitamin C needs to play a role in your daily intake.
Nathan Goodyear

Raw Garlic Consumption as a Protective Factor for Lung Cancer, a Population-Based Case-... - 0 views

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    Garlic intake at twice weekly reduces lung cancer rates in smokers and non-smokers.  The component that provides the benefit is Aillicin.  This study only looked at raw garlic intake.  
Nathan Goodyear

Influence of ghrelin on food ... [Curr Opin Clin Nutr Metab Care. 2007] - PubMed - NCBI - 0 views

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    Ghrelin is an orexin that increases energy intake i.e. increases food intake.
Nathan Goodyear

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

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

Fructose: A Key Factor in the Development of Metabolic Syndrome and Hypertension - 0 views

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    Fructose intake increases MetS and hypertension.  The high fructose intake upregulates phosphofructokinase which increases triglyceride production, bypassing central regulation.  This results in ATP depletion with reduced capacity to recover.  Thus attempts by the cells to increase ATP through AMP deaminase results in uric acid production.
Nathan Goodyear

PLOS ONE: Healthy Lifestyles Reduce the Incidence of Chronic Diseases and Dementia: Evi... - 0 views

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    Despite evidence that non-smoking, normal BMI, regular exercise, high fruit/vegetable intake and low/moderate alcohol intake, less than 1% of men change lifestyle.  Translation:  many don't want health even when presented with evidence of its benefits and the means to achieve it.   This study found a decrease in cognitive decline in individuals undergoing these lifestyle changes.
Nathan Goodyear

Omega-3 fatty acid supplementation and reduction... [J Neurosurg. 2011] - PubMed - NCBI - 0 views

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    Animal model shows that n-3 intake reduced axonal injury after injury insult.  This implies a use in n-3 intake even after an insult has occured. This implies a role for n-3 in neuroplasticity.
Nathan Goodyear

Overactivation of S6 Kinase 1 as a Cause of Human Insulin Resistance During Increased A... - 0 views

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    High protein intake can lead to insulin resistance.  Glucose regulation by insulin and skeletal muscle removal of glucose is disrupted by high amino acid intake through disruption of secondary insulin signaling.
Nathan Goodyear

Nutritional Modulation of Insulin Resistance - 0 views

  • Five branched chain and aromatic amino acids (isoleucine, leucine, valine, tyrosine, and phenylalanine) showed significant associations with future diabetes
  • there is increasing evidence that longer term high-protein intake may have detrimental effects on insulin resistance [68, 117–123], diabetes risk [69], and the risk of developing cardiovascular disease
  • high-protein and the high GI diets significantly increased markers of low-grade inflammation
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  • significant and clinically relevant worsening of insulin sensitivity with an isoenergetic plant-based high-protein diet
  • healthy humans that are exposed to amino acid infusions rapidly develop insulin resistance
  • longer term high-protein intake has been shown to result in whole-body insulin resistance [68, 118], associated with upregulation of factors involved in the mammalian target of rapamycin (mTOR)/S6K1 signalling pathway [68], increased stimulation of glucagon and insulin within the endocrine pancreas, high glycogen turnover [118] and stimulation of gluconeogenesis [68, 118].
  • it was recently shown in a large prospective cohort with 10 years followup that consuming 5% of energy from both animal and total protein at the expense of carbohydrates or fat increases diabetes risk by as much as 30% [69]. This reinforces the theory that high-protein diets can have adverse effects on glucose metabolism.
  • Another recent study showed that low-carbohydrate high-protein diets, used on a regular basis and without consideration of the nature of carbohydrates or the source of proteins, are also associated with increased risk of cardiovascular disease [70], thereby indicating a potential link between high-protein Western diets, T2DM, and cardiovascular risk.
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    macronutrient intake and effect on glucose regulation and thus metabolism.
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