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
shared by Nathan Goodyear on 16 Sep 13
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For thousands of years humans consumed fructose amounting to 16–20 grams per day
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daily consumptions amounting to 85–100 grams of fructose per day
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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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A prolonged elevation of TG was also seen in the high fructose subjects
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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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Chronic fructose consumption reduces adiponectin responses, contributing to insulin resistance
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A definite relationship has also been found between metabolic syndrome and hyperhomocysteinemia
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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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Fructose stimulates TG production, but impairs removal, creating the known dyslipidemic profile
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the effects of fructose in promoting TG synthesis are independent of insulinemia
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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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High fructose diets can have a hypertriglyceridemic and pro-oxidant effect
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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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Fructose has also been implicated in reducing PPARα levels
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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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decreased PPARα expression can result in reduced oxidation, leading to cellular lipid accumulation
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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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LDL particle size has been found to be inversely related to TG concentration
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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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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.
