Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

An imbalance between triacylglycerol synthesis and breakdown is necessary for the development of obesity. The direct precursor for triacylglycerol biosynthesis is alpha-glycerol phosphate, which can have glycolytic and glyceroneogenic origins. We present a technique for determining the relative glyceroneogenic contribution to triacylglyceride glycerol by labeling the glycerol moiety with 2H2O. The number of hydrogen atoms (n) incorporated from H2O into C-H bonds reflects the metabolic source of alpha-glycerol phosphate and can be calculated by combinatorial analysis of the distribution of mass isotopomers in triacylglyceride glycerol. Three physiological settings with potential effects on glyceroneogenesis and glycolysis were studied in rodents. Adipose tissue acylglyceride glycerol in mice fed a low carbohydrate diet had significantly higher values of n than in mice fed a high carbohydrate diet, suggesting an increased contribution from glyceroneogenesis of from 17 to 50% on the low carbohydrate diet. Similarly, mice administered rosiglitazone had a significant relative increase in glyceroneogenesis (from 17 to 53%), indicated by an increase in adipose acylglyceride glycerol n. Fructose infusion in overnight fasted rats rapidly lowered plasma triacylglyceride glycerol n, reflecting a decreased contribution from glyceroneogenesis (from 66 to 34%) presumably because of increased glycolytic input. In conclusion, we demonstrate that the number of C-H atoms derived from cellular H2O in triacylglyceride glycerol is an informative indicator of alpha-glycerol phosphate origin and, ultimately, triacylglycerol metabolism. Under certain physiological conditions, glyceroneogenesis can be up-regulated in adipose (e.g. low carbohydrate diet) or down-regulated in liver (e.g. fructose infusion). Additionally, stimulation of glyceroneogenesis by rosiglitazone in adipose tissue may be an important factor in the antilipolytic actions of thiazolidinediones.
 ...
PMID:Physiologic and pharmacologic factors influencing glyceroneogenic contribution to triacylglyceride glycerol measured by mass isotopomer distribution analysis. 1588 53

Insulin resistance (hyperinsulinaemia) is now recognized as a major contributor to the development of glucose intolerance, dyslipidaemia and hypertension in non-insulin-dependent diabetes mellitus (NIDDM) patients. Sedentary lifestyle, consumption of energy-rich diet, obesity, longer lifespan, etc., are important reasons for this rise (J. R. Turtle, Int J Clin Prac 2000; 113: 23). Aqueous extracts of Pterocarpus marsupium Linn bark (PM), Ocimum sanctum Linn leaves (OS) and Trigonella foenumgraecum Linn seeds (FG) have been shown to exert hypoglycaemic/antihyperglycaemic effect in experimental as well as clinical setting. As no work has been carried out so far to assess the effect of PM, OS and FG on fructose-induced hyperglycaemia, hyperinsulinaemia and hypertriglyceridaemia, we undertook this study to assess whether these extracts attenuate the metabolic alteration induced by fructose-rich diet in rats. Five groups of rats (eight each) were fed chow diet, 66% fructose diet, 66% fructose diet + PM leaves extract (1 g/kg/day), 66% fructose diet + OS leaves extract (200 mg/kg/day) and 66% fructose diet + FG seeds extract (2 g/kg/day) for 30 days. Fructose feeding to normal rats for 30 days significantly increased serum glucose, insulin and triglyceride levels in comparison with control. Treatment with all the three plants extract for 30 days significantly lowered the serum glucose levels in comparison with control group. However, only PM extract substantially prevented hypertriglyceridaemia and hyperinsulinaemia, while OS and FG had no significant effect on these parameters. Results of this study, in addition to previous clinical benefits of PM seen in NIDDM subjects, are suggestive of usefulness of PM bark (Vijayasar) in insulin resistance, the associated disorder of type 2 diabetes; however, OS and FG may not be useful. Though several antidiabetic principles (-epicatechin, pterosupin, marsupin and pterostilbene) have been identified in the PM, yet future studies are required to certify their efficacy and safety before clinical scenario.
 ...
PMID:Pterocarpus marsupium extract (Vijayasar) prevented the alteration in metabolic patterns induced in the normal rat by feeding an adequate diet containing fructose as sole carbohydrate. 1595 28

Fructose intake and the prevalence of obesity have both increased over the past two to three decades. Compared with glucose, the hepatic metabolism of fructose favors lipogenesis, which may contribute to hyperlipidemia and obesity. Fructose does not increase insulin and leptin or suppress ghrelin, which suggests an endocrine mechanism by which it induces a positive energy balance. This review examines the available data on the effects of dietary fructose on energy homeostasis and lipid/carbohydrate metabolism. Recent publications, studies in human subjects, and areas in which additional research is needed are emphasized.
 ...
PMID:Dietary fructose: implications for dysregulation of energy homeostasis and lipid/carbohydrate metabolism. 1597 9

The worldwide epidemic of metabolic syndrome correlates with an elevation in serum uric acid as well as a marked increase in total fructose intake (in the form of table sugar and high-fructose corn syrup). Fructose raises uric acid, and the latter inhibits nitric oxide bioavailability. Because insulin requires nitric oxide to stimulate glucose uptake, we hypothesized that fructose-induced hyperuricemia may have a pathogenic role in metabolic syndrome. Four sets of experiments were performed. First, pair-feeding studies showed that fructose, and not dextrose, induced features (hyperinsulinemia, hypertriglyceridemia, and hyperuricemia) of metabolic syndrome. Second, in rats receiving a high-fructose diet, the lowering of uric acid with either allopurinol (a xanthine oxidase inhibitor) or benzbromarone (a uricosuric agent) was able to prevent or reverse features of metabolic syndrome. In particular, the administration of allopurinol prophylactically prevented fructose-induced hyperinsulinemia (272.3 vs.160.8 pmol/l, P < 0.05), systolic hypertension (142 vs. 133 mmHg, P < 0.05), hypertriglyceridemia (233.7 vs. 65.4 mg/dl, P < 0.01), and weight gain (455 vs. 425 g, P < 0.05) at 8 wk. Neither allopurinol nor benzbromarone affected dietary intake of control diet in rats. Finally, uric acid dose dependently inhibited endothelial function as manifested by a reduced vasodilatory response of aortic artery rings to acetylcholine. These data provide the first evidence that uric acid may be a cause of metabolic syndrome, possibly due to its ability to inhibit endothelial function. Fructose may have a major role in the epidemic of metabolic syndrome and obesity due to its ability to raise uric acid.
 ...
PMID:A causal role for uric acid in fructose-induced metabolic syndrome. 1623 13

The consumption of fructose, primarily from high-fructose corn syrup (HFCS), has increased considerably in the United States during the past several decades. Intake of HFCS may now exceed that of the other major caloric sweetener, sucrose. Some nutritionists believe fructose is a safer form of sugar than sucrose, particularly for people with diabetes mellitus, because it does not adversely affect blood-glucose regulation, at least in the short-term. However, fructose has potentially harmful effects on other aspects of metabolism. In particular, fructose is a potent reducing sugar that promotes the formation of toxic advanced glycation end-products, which appear to play a role in the aging process; in the pathogenesis of the vascular, renal, and ocular complications of diabetes; and in the development of atherosclerosis. Fructose has also been implicated as the main cause of symptoms in some patients with chronic diarrhea or other functional bowel disturbances. In addition, excessive fructose consumption may be responsible in part for the increasing prevalence of obesity, diabetes mellitus, and non-alcoholic fatty liver disease. Although the long-term effects of fructose consumption have not been adequately studied in humans, the available evidence suggests it may be more harmful than is generally recognized. The extent to which a person might be adversely affected by dietary fructose depends both on the amount consumed and on individual tolerance. With a few exceptions, the relatively small amounts of fructose that occur naturally in fruits and vegetables are unlikely to have deleterious effects, and this review is not meant to discourage the consumption of these healthful foods.
 ...
PMID:Adverse effects of dietary fructose. 1636 38

Fructose is a monosaccharide which is abundant in nature. It is the sweetest naturally occurring carbohydrate. The availability of fructose increased substantially when it became possible in the 1960s to economically produce high fructose syrups from corn starch and other starches. Such high fructose syrups are now used to sweeten soft drinks, fruit drinks, baked goods, jams, syrups and candies. The most recent data available suggest that fructose consumption is increasing worldwide. Fructose presently accounts for about 10% of average total energy intake in the United States. Studies in both healthy and diabetic subjects demonstrated that fructose produced a smaller postprandial rise in plasma glucose and serum insulin than other common carbohydrates. Substitution of dietary fructose for other carbohydrates produced a 13% reduction in mean plasma glucose in a study of type-1 and type-2 diabetic subjects. However, there is concern that fructose may aggravate lipemia, particularly in men. In one study, daylong plasma triglycerides (estimated by determining the area under response curves) in healthy men was 32% greater during a high fructose diet than during a high glucose diet. There is also concern that fructose may be a factor contributing to the growing worldwide prevalence of obesity. Increasing fructose consumption is temporally associated with the increase in obesity. Moreover, on theoretical grounds, dietary fructose might increase energy intake. Fructose stimulates insulin secretion less than does glucose and glucose-containing carbohydrates. Since insulin increases leptin release, lower circulating insulin and leptin after fructose ingestion might inhibit appetite less than consumption of other carbohydrates and lead to increased energy intake. However, there is not yet any convincing experimental evidence that dietary fructose does increase energy intake. Although evidence that fructose has adverse effects is limited, adding fructose in large amounts to the diet may be undesirable, particularly for men. Fructose that occurs naturally in fruits and vegetables is a modest component of energy intake and should not be of concern.
 ...
PMID:Is fructose the optimal low glycemic index sweetener? 1682 Jul 33

The increasing incidence of obesity and the metabolic syndrome over the past two decades has coincided with a marked increase in total fructose intake. Fructose--unlike other sugars--causes serum uric acid levels to rise rapidly. We recently reported that uric acid reduces levels of endothelial nitric oxide (NO), a key mediator of insulin action. NO increases blood flow to skeletal muscle and enhances glucose uptake. Animals deficient in endothelial NO develop insulin resistance and other features of the metabolic syndrome. As such, we propose that the epidemic of the metabolic syndrome is due in part to fructose-induced hyperuricemia that reduces endothelial NO levels and induces insulin resistance. Consistent with this hypothesis is the observation that changes in mean uric acid levels correlate with the increasing prevalence of metabolic syndrome in the US and developing countries. In addition, we observed that a serum uric acid level above 5.5 mg/dl independently predicted the development of hyperinsulinemia at both 6 and 12 months in nondiabetic patients with first-time myocardial infarction. Fructose-induced hyperuricemia results in endothelial dysfunction and insulin resistance, and might be a novel causal mechanism of the metabolic syndrome. Studies in humans should be performed to address whether lowering uric acid levels will help to prevent this condition.
 ...
PMID:Hypothesis: fructose-induced hyperuricemia as a causal mechanism for the epidemic of the metabolic syndrome. 1693 73

Fructose 2,6-bisphosphate (Fru-2,6-P2) is an important metabolite that controls glycolytic and gluconeogenic pathways in several cell types. Its synthesis and degradation are catalyzed by the bifunctional enzyme 6-phosphofructo-2-kinase/fructose 2,6-bisphosphatase (PFK-2). Four genes, designated Pfkfb1-4, codify the different PFK-2 isozymes. The Pfkfb3 gene product, ubiquitous PFK-2 (uPFK-2), has the highest kinase/bisphosphatase activity ratio and is associated with proliferation and tumor metabolism. A transgenic mouse model that overexpresses uPFK-2 under the control of the phosphoenolpyruvate carboxykinase promoter was designed to promote sustained and elevated Fru-2,6-P2 levels in the liver. Our results demonstrate that in diet-induced obesity, high Fru-2,6-P2 levels in transgenic livers caused changes in hepatic gene expression profiles for key gluconeogenic and lipogenic enzymes, as well as an accumulation of lipids in periportal cells, and weight gain.
 ...
PMID:Overexpression of ubiquitous 6-phosphofructo-2-kinase in the liver of transgenic mice results in weight gain. 1799 24

Fructose consumption in the USA has increased over the past three decades. During this time, obesity, insulin resistance and the metabolic syndrome have also increased in prevalence. While diets high in fructose have been shown to promote insulin resistance and increase TAG concentrations in animals, there are insufficient data available regarding the long-term metabolic effects of fructose consumption in humans. The objective of the present study was to investigate the metabolic effects of 10-week consumption of fructose-sweetened beverages in human subjects under energy-balanced conditions in a controlled research setting. Following a 4-week weight-maintaining complex carbohydrate diet, seven overweight or obese (BMI 26.8-33.3 kg/m2) postmenopausal women were fed an isoenergetic intervention diet, which included a fructose-sweetened beverage with each meal, for 10 weeks. The intervention diet provided 15 % of energy from protein, 30 % from fat and 55 % from carbohydrate (30 % complex carbohydrate, 25 % fructose). Fasting and postprandial glucose, insulin, TAG and apoB concentrations were measured. Fructose consumption increased fasting glucose concentrations and decreased meal-associated glucose and insulin responses (P = 0.0002, P = 0.007 and P = 0.013, respectively). Moreover, after 10 weeks of fructose consumption, 14 h postprandial TAG profiles were significantly increased, with the area under the curve at 10 weeks being 141 % higher than at baseline (P = 0.04). Fructose also increased fasting apoB concentrations by 19 % (P = 0.043 v. baseline). In summary, consumption of fructose-sweetened beverages increased postprandial TAG and fasting apoB concentrations, and the present results suggest that long-term consumption of diets high in fructose could lead to an increased risk of CVD.
 ...
PMID:Consumption of fructose-sweetened beverages for 10 weeks increases postprandial triacylglycerol and apolipoprotein-B concentrations in overweight and obese women. 1838 5

Fructose is now such an important component of human diets that increasing attention is being focused on the fructose transporter GLUT5. In this review, we describe the regulation of GLUT5 not only in the intestine and testis, where it was first discovered, but also in the kidney, skeletal muscle, fat tissue, and brain where increasing numbers of cell types have been found to have GLUT5. GLUT5 expression levels and fructose uptake rates are also significantly affected by diabetes, hypertension, obesity, and inflammation and seem to be induced during carcinogenesis, particularly in the mammary glands. We end by highlighting research areas that should yield information needed to better understand the role of GLUT5 during normal development, metabolic disturbances, and cancer.
 ...
PMID:Regulation of the fructose transporter GLUT5 in health and disease. 1839 11


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>