For thousands
of years humans consumed fructose amounting to 16–20 grams per day
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Nutrition & Metabolism | Full text | Fructose, insulin resistance, and metabolic dyslip... - 0 views
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fructose metabolic syndrome metabolic syndrome insulin resistance obesity nutrition metabolism
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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]).
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Glycemic excursions and insulin responses were reduced by 66% and 65%, respectively, in the fructose-consuming subjects
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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.
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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
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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
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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
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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
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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
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Carbohydrate induced hypertriglycerolemia results from a combination of both TG overproduction, and inadequate TG clearance
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fructose-induced metabolic dyslipidemia is usually accompanied by whole body insulin resistance [100] and reduced hepatic insulin sensitivity
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Excess VLDL secretion has been shown to deliver increased fatty acids and TG to muscle and other tissues, further inducing insulin resistance
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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
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Oxidative stress has often been implicated in the pathology of insulin resistance induced by fructose feeding
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Administration of alpha-lipoic acid (LA) has been shown to prevent these changes, and improve insulin sensitivity
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LA treatment also prevents several deleterious effects of fructose feeding: the increases in cholesterol, TG, activity of lipogenic enzymes, and VLDL secretion
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PPARα is a ligand activated nuclear hormone receptor that is responsible for inducing mitochondrial and peroxisomal β-oxidation
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fructose diets altered the structure and function of VLDL particles causing and increase in the TG: protein ratio
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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
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High fructose, which stimulates VLDL secretion, may initiate the cycle that results in metabolic syndrome long before type 2 diabetes and obesity develop
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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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Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse ... - 0 views
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Fructose, weight gain, and the insulin resistance syndrome - 0 views
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he combined effects of lowered circulating leptin and insulin in individuals who consume diets that are high in dietary fructose could therefore increase the likelihood of weight gain and its associated metabolic sequelae
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Fructose consumption induces insulin resistance, impaired glucose tolerance, hyperinsulinemia, hypertriacylglycerolemia, and hypertension in animal models
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Obesity - Systemic Inflammation, Adipose Tissue Tumor Necrosis Factor, and Leptin Expre... - 0 views
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The kisspeptin-GnRH pathway in human reproductive health and disease - 0 views
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This raises the possibility that diminished kisspeptin secretion is a potential mechanism for hypogonadotropic hypogonadism in patients with obesity and diabetes
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The likely pathways for down-regulation of kisspeptin signalling include negative feedback by estrogen, which is markedly elevated in obesity (Schneider et al., 1979), resistance to leptin, also seen in human obesity (Finn et al., 1998), insulin resistance and hyperglycaemia (Castellano et al., 2006, 2009), and inflammation, which is up-regulated in hypogonadal men with diabetes (Dandona et al., 2008) and is associated with decreased kisspeptin expression in rats
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shared by Nathan Goodyear on 27 Oct 14
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http://www.eurjmedres.com/content/pdf/s40001-014-0056-6.pdf - 0 views
www.eurjmedres.com/...s40001-014-0056-6.pdf
Testosterone therapy treatment diet exercise low T low Testosterone low T Diabetes BMI weight HgbA1c hypertension blood pressure men male hormone hormones
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Testosterone therapy in obese men with type II Diabetes and low T improved weight, lipids, HgbA1c, and blood pressure. There was more improvement with Leptin than with diet/exercise alone. What is very important is that the control group (diet, exercise, DM meds) had improvement in Testosterone levels, HgbA1c, lipids, BMI, and blood pressure; just not as strong as the treatment arm with Testosterone.
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IL-1 family in breast cancer: Potential interplay with leptin and other adipocytokines ... - 0 views
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obesity Adiponectin IL-6 adipocytes Leptin inflammation cancer IL-1
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Obesity is biologically active, both from a hormonal and inflammatory perspective. No matter what marketing may try to say, obesity is not a "new health". Inflammatory signaling, i.e. IL-1, IL-6... are increased from the biological adipocytes in obesity. These can lead to cancer development and progression.
Linkage Between Obesity Leptin and Breast Cancer - Manar Fayiz Atoum, Foad Alzoughool, ... - 0 views
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shared by Nathan Goodyear on 13 Nov 12
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Testosterone, the male hormone connection: treating diabetes and heart disease. - 0 views
www.worldhealth.net/...thera6_ch7.pdf
testosterone low T low testosterone CVD cardiovascular disease diabetes insulin leptin ghrelin PAI-1 obesity adiponectin type II diabetes DM atherosclerosis
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Mood Disorders and Obesity: Understanding Inflammation as a Pathophysiological Nexus | ... - 0 views
www.academia.edu/..._as_a_Pathophysiological_Nexus
obesity overweight mood disorders depression anxiety weight loss' leptin adiponectin inflammation cytokines
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shared by Nathan Goodyear on 17 Oct 12
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Androgens in Polycystic Ovary Syndrome: The Role of Exercise and Diet - 0 views
www.baselinefitness.com/PCOS%20review.pdf
PCOS diet exercise women androgens testosterone insulin resistance inflammation leptin gherlin
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Effects of dietary polyphenols on neuroregulatory factors and pathways that mediate foo... - 0 views
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The effects of metformin and diet on plasma testosterone and leptin levels in obese men... - 0 views
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shared by Nathan Goodyear on 28 Aug 12
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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
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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
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most serum laboratories offer a free testosterone level, which is a calculated value based on SHBG levels or determined with equilibrium dialysis
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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
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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
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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.
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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
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Leptin, an adipose-derived peptide hormone that regulates appetite and metabolism, has been shown to directly inhibit testosterone production in animal models
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tumor necrosis factor alpha (TNF-alpha) and interleukin-1 (IL-1) further inhibit Leydig cell testosterone production
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there are several herbs that can work to boost testosterone levels, including longjack (Eurycoma longifolia), horny goat weed (Epimedium grandiflorum), and tribulus (Tribulus terrestris).
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the majority of the hormone is bound to carrier proteins including sex hormone binding globulin (SHBG) and albumin
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shared by Nathan Goodyear on 10 Jan 12
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Inflammation and insulin resistance 10.1016/j.febslet.2007.11.057 : FEBS Letters | Scie... - 0 views
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inflammation insulin resistance IR PPAR TNF-alpha IL-6 IL-10 IL-1Beta JNK GLT-4 Resistin adiponectin Gherlin NF-kapppB iNOS lkkb obesity TLR-4
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A subsequent study by Yuan et al. showed that Tnf treatment of 3T3L1 adipocytes induces insulin resistance and that this could be prevented by pretreatment of cells with aspirin
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the percentage of macrophages in a given adipose tissue depot is positively correlated with adiposity and adipocyte size
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Il-10 exerts its anti-inflammatory activity by inhibiting Tnf-induced NFκB activation by reducing IKK activity [38]
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adipose tissue macrophages are responsible for nearly all adipose tissue Tnf expression and a significant portion of Nos2 and Il6 expression
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One theory holds that the expansion of adipose tissue leads to adipocyte hypertrophy and hyperplasia and that large adipocytes outstrip the local oxygen supply leading to cell autonomous hypoxia with activation of cellular stress pathways
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The use of the anti-inflammatory compounds, salicylate and its derivative aspirin, for treating symptoms of T2DM dates back over 100 years
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elevated levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin (IL-8) have all been reported in various diabetic and insulin resistant states
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overnutrition and obesity are often accompanied by elevations in tissue and circulating FFA concentrations, and saturated FFAs can directly activate pro-inflammatory responses
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Adipokines such as resistin, leptin and adiponectin, which are secreted by adipocytes, can also affect inflammation and insulin sensitivity
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In skeletal muscle insulin promotes glucose uptake by stimulating translocation of the GLUT4 glucose transporter
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macrophages are also capable of undergoing a phenotypic switch from an M1 state, which was defined as the “classically activated” pro-inflammatory macrophage, to the M2 state or the “alternatively activated” non-inflammatory cell
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Several inducers of insulin resistance, including FFAs, pro-inflammatory cytokines and oxidative stress, activate the expression of Nos2, the gene that encodes iNOS (reviewed in [33]
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Adipose tissue insulin signaling results in decreased hormone sensitive lipase activity and this anti-lipolytic effect inhibits free fatty acid (FFA) efflux out of adipocytes.
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In the liver, insulin inhibits the expression of key gluconeogenic enzymes and, therefore, insulin resistance in liver leads to elevated hepatic glucose production
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elevated JNK activity in liver, adipose tissue and skeletal muscle of obese insulin resistant mice, and knockout of Jnk1 (Jnk1−/−) leads to amelioration of insulin resistance in high fat diet
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Adipose tissue from obese mice contains proportionately more M1 macrophages, whereas, lean adipose tissue contains more M2 macrophages, and increased M1 content positively correlates with inflammation, macrophage infiltration and insulin resistance
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these studies highlight the possibility that increased iNOS activity plays a direct role in the pathogenesis of insulin resistance
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the important role of Ikkb in the development of obesity and inflammation-induced insulin resistance.
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It is probable that local concentrations of inflammatory mediators, such as FFAs, Tnf or other cytokines/adipokines contribute to this polarity switch
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Tnf and other cytokines/chemokines are symptomatic of inflammation, and while they propagate and/or maintain the inflammatory state, they are not the initial cause(s) of inflammation
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Tlr4, in particular, is stimulated by lipopolysaccharide (LPS), an endotoxin released by gram-negative bacteria
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Tlr4 belongs to the family of Toll-like receptors that function as pattern recognition receptors that guard against microorganismal infections as part of the innate immune system.
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Tlr4 stimulation results in the activation of both Ikkb/NFκB and JNK/AP-1 signaling, culminating in the expression and secretion of pro-inflammatory cytokines/chemokines, including, Il1b, IL-6, Tnf, Mcp1, etc. (reviewed in [57
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shared by Nathan Goodyear on 12 Jan 12
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Adipocytokines and Insulin Resistance - 0 views
jcem.endojournals.org/...447.full
insulin resistance obesity leptin resistin adiponectin adipocytokines TNF-alpha IL-6 inflammation
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shared by Nathan Goodyear on 28 Feb 12
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Central Nervous system control of food intake - 0 views
www.saegre.org.ar/...schwartz_2000.pdf
CNS gut eating overeating obesity overweight weight-loss leptin insulin ghrelin adiponectin
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shared by Nathan Goodyear on 15 Jan 14
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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
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The number of overweight people is expected to increase from 937 million in 2005 to 1.35 billion in 2030
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Similarly the number of obese people is projected to increase from 396 million in 2005 to 573 million in 2030
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By 2030, China alone is predicted to have more overweight men and women than the traditional market economies combined
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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.
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The fact that obese men have lower testosterone compared to lean men has been recognized for more than 30 years
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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.
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obesity blunts this LH rise, obesity leads to hypothalamic-pituitary suppression irrespective of age which cannot be compensated for by physiological mechanisms
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Reductions in total testosterone levels are largely a consequence of reductions in sex hormone binding globulin (SHBG) due to obesity-associated hyperinsulinemia
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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
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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
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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
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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
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In the prospective Massachusetts Male Aging Study (MMAS), moving from a non-obese to an obese state resulted in a decline of testosterone levels
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weight loss, whether by diet or surgery, increases testosterone levels proportional to the amount of weight lost
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Testosterone enhances catecholamine-induced lipolysis in vitro and reduces lipoprotein lipase activity and triglyceride uptake in human abdominal adipose tissue in vivo
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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
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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
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men undergoing androgen depletion for prostate cancer show more marked increases in visceral compared to subcutaneous fat following treatment
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androgens can act via the PPARg-pathway [37] which is implicated in the differentiation of precursor fat cells to the energy-consuming phenotype
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low testosterone may compound the effect of increasing fat mass by making it more difficult for obese men to lose weight via exercise
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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
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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;
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observational evidence associating higher endogenous testosterone with reduced loss of muscle mass and crude measures of muscle function in men losing weight
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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
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Testosterone and glucose metabolism in men: current concepts and controversies - 0 views
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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
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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
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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
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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
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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
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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
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This is supported by observational studies showing that weight gain and development of diabetes accelerate the age-related decline in testosterone
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The hypothalamic–pituitary–testicular axis remains responsive to treatment with aromatase inhibitors or selective oestrogen receptor modulators in obese men
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Kisspeptin treatment increases LH secretion, pulse frequency and circulating testosterone levels in hypotestosteronaemic men with type 2 diabetes
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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
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This suggests that weight loss can lead to genuine reactivation of the gonadal axis by reversal of obesity-associated hypothalamic suppression
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There is pre-clinical and observational evidence that chronic hyperglycaemia can inhibit the HPT axis
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successful weight loss combined with optimisation of glycaemic control may be sufficient to normalise circulating testosterone levels in the majority of such men
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weight loss, optimisation of diabetic control and assiduous care of comorbidities should remain the first-line approach.
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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
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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).
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Effects of testosterone therapy on body composition were metabolically favourable with modest decreases in fat mass and increases in lean body mass
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This suggests that testosterone has limited effects on glucose metabolism in relatively healthy men with only mildly reduced testosterone.
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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.
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the evidence from controlled studies show that testosterone therapy consistently reduces fat mass and increases lean body mass, but inconsistently decreases insulin resistance.
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Interestingly, testosterone therapy does not consistently improve glucose metabolism despite a reduction in fat mass and an increase in lean mass
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the majority of RCTs (recently reviewed in Ng Tang Fui et al. (2013a)) showed that testosterone therapy does not reduce visceral fat
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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
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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
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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.
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data have not shown evidence that testosterone causes prostate cancer, or that it makes subclinical prostate cancer grow
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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