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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The aim of this study was to investigate whether the central nervous system regulates mucosal cell growth and apoptosis in the rat small intestine. Ornithine decarboxylase is a key enzyme for polyamine synthesis, which plays an important role in intestinal mucosal growth. The increase in ornithine decarboxylase activity in the duodenum just before a dark period was abolished by truncal vagotomy. An infusion of 2-deoxy-D-glucose into the third cerebroventricle activated the enzyme activity in the small intestine. Epithelial homeostasis is balanced by the regulation of cell proliferation and cell death. Intestinal mucosal apoptosis decreased in rats with ventromedial hypothalamus lesions, which induced hyperphagia and obesity. In contrast, sustained anorexia induced by 1-deoxy-D-glucosamine increased intestinal apoptosis. These results indicate that the central nervous system, in addition to local factors, is related to the regulation of mucosal homeostasis in the intestinal mucosa.
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PMID:Homeostasis in the small intestinal mucosa balanced between cell proliferation and apoptosis is regulated partly by the central nervous system. 1257 82

A role for the sympathetic nervous system in hypertension has been looked for in relation to the 'metabolic syndrome' with associations between body weight, insulin sensitivity and hypertension. By use of microneurography human sympathetic responses to hypoglycaemia, normoglycaemic hyperinsulinaemia and food intake have been studied. A strong but differentiated influence of insulin-induced hypoglycaemia comprises increase in muscle sympathetic nerve activity (MSNA) and the sudomotor part of skin sympathetic nerve activity (SSNA), whereas vasoconstrictor SSNA is inhibited. Responses to infusion of 2-deoxy-D-glucose are identical, suggesting central nervous system glucopenia and not insulin to be the causative factor. Insulin infusion during normoglycaemia evokes a moderate increase in MSNA; SSNA and blood pressure does not change. After glucose ingestion MSNA displays a sustained increase, which is only partly elicited by insulin. A significant albeit weaker increase occurs after pure protein or fat meals, and after glucose ingestion in C-peptide-negative diabetic patients, with no insulin secretion. In healthy elderly people the MSNA response to food intake is weak, because of a high outflow already at rest; this is suggested to explain postprandial hypotension in the elderly, a paradoxical mechanism behind clinical autonomic failure. A pathophysiological role of MSNA in the metabolic syndrome with hypertension has been speculated. An association between obesity and elevated level of MSNA at rest is established; observed relationships to chronic insulin levels and hypertension are less unanimous. The adipose tissue regulating hormone leptin has become one focus of interest in ongoing attempts to elucidate a possible role of the human sympathetic nervous system in the 'metabolic syndrome' and hypertension.
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PMID:Sympathetic nerve activity in metabolic control--some basic concepts. 1260 4

A controversial area in understanding the contribution of obesity to skeletal muscle insulin resistance is the distribution of control of glucose metabolism across proximal steps of glucose delivery, trans-membrane transport, and intracellular trapping via phosphorylation. Dynamic positron emission tomography (PET) imaging of skeletal muscle [(18)F]2-deoxy-2-D-glucose ((18)F-FDG) uptake provides an in vivo method for assessment of these steps in humans. In the current study we have examined the application of a four-compartment skeletal muscle-specific model for assessment of (18)F-FDG metabolism that takes interstitial (18)F-FDG kinetics into account and compared this to the classic three-compartment model in lean and obese volunteers. We assessed the effects of insulin infusions at three rates (0, 40, and 120 mU/m(2).min). In comparison with the classic model, the skeletal muscle-specific model reveals more clearly definable effects of insulin on transmembrane glucose transport and an impairment of this response in obesity. Compared with the classic model for assessment of (18)F-FDG metabolism, both the skeletal muscle-specific and the classic model indicate that, with respect to distribution of control, glucose phosphorylation has an important effect at low to moderate levels of insulin stimulation in both lean and obese subjects.
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PMID:Glucose transport and phosphorylation in skeletal muscle in obesity: insight from a muscle-specific positron emission tomography model. 1262 18

Anthocyanins, which are used as a food coloring, are widely distributed in human diets, suggesting that we ingest large amounts of anthocyanins from plant-based foods. Mice were fed control, cyanidin 3-glucoside-rich purple corn color (PCC), high fat (HF) or HF + PCC diet for 12 wk. Dietary PCC significantly suppressed the HF diet-induced increase in body weight gain, and white and brown adipose tissue weights. Feeding the HF diet markedly induced hypertrophy of the adipocytes in the epididymal white adipose tissue compared with the control group. In contrast, the induction did not occur in the HF + PCC group. The HF diet induced hyperglycemia, hyperinsulinemia and hyperleptinemia. These perturbations were completely normalized in rats fed HF + PCC. An increase in the tumor necrosis factor (TNF)-alpha mRNA level occurred in the HF group and was normalized by dietary PCC. These results suggest that dietary PCC may ameliorate HF diet-induced insulin resistance in mice. PCC suppressed the mRNA levels of enzymes involved in fatty acid and triacylglycerol synthesis and lowered the sterol regulatory element binding protein-1 mRNA level in white adipose tissue. These down-regulations may contribute to triacylglycerol accumulation in white adipose tissue. Our findings provide a biochemical and nutritional basis for the use of PCC or anthocyanins as a functional food factor that may have benefits for the prevention of obesity and diabetes.
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PMID:Dietary cyanidin 3-O-beta-D-glucoside-rich purple corn color prevents obesity and ameliorates hyperglycemia in mice. 1284 Jan 66

Insulin-resistant states such as obesity can result in an increase in the function and mass of pancreatic beta-cells, so that insulin secretion is up-regulated and Type II diabetes does not develop. However, expansion of beta-cell mass is not indefinite and may well decrease with time. Changes in circulating concentrations of nutritional factors, such as fatty acids and/or glucose, may lead to a reduction in beta-cell mass in vivo. Few previous studies have attempted to explore the interplay between glucose, amino acids and fatty acids with respect to beta-cell mass and functional integrity. In the present study, we demonstrate that culture of clonal BRIN-BD11 cells for 24 h with the polyunsaturated fatty acid arachidonic acid (AA) increased beta-cell proliferation and enhanced alanine-stimulated insulin secretion. These effects of AA were associated with significant decreases in the cellular consumption of D-glucose and L-alanine as well as decreased rates of production of nitric oxide and ammonia. Conversely 24 h exposure to the saturated fatty acid palmitic acid (PA) was found to decrease beta-cell viability (by increasing apoptosis), increase the intracellular concentration of triacylglycerol (triglyceride), while inhibiting alanine-stimulated insulin secretion. These effects of PA were associated with significant increases in D-glucose and L-glutamine consumption as well as nitric oxide and ammonia production. However, L-alanine consumption was decreased in the presence of PA. The effects of AA, but not PA, were additionally dependent on glucose concentration. These studies indicate that AA may have a critical role in maintaining the appropriate mass and function of islet beta-cells by influencing rates of cell proliferation and insulin secretion. This regulatory effect may be compromised by high circulating levels of glucose and/or PA, both of which are elevated in Type II diabetes and may impact upon dysfunctional and apoptotic intracellular events in the beta-cell.
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PMID:Arachidonic acid, palmitic acid and glucose are important for the modulation of clonal pancreatic beta-cell insulin secretion, growth and functional integrity. 1456 Dec 12

Glucomannan is a dietary fiber employed quite frequently in the western countries since two decades now, as its ingestion plays an important role in human health. However, eastern people have used this fiber for more than a thousand years. This dietary fiber is the main polysaccharide obtain from the tubers of the Amorphophallus konjac plant, a member of the family Araceae found in east Asia. The chemical structure of glucomannan consists, mainly, in mannose and glucose in the ratio 8:5 linked by beta (1-->4) glycosidic bonds. This soluble fiber has a extraordinarily high waterholding capacity, forming highly viscous solutions when dissolved in water. It has the highest molecular weight and viscosity of any known dietary fiber. It has been demonstrated that this product is highly effective in the treatment of obesity due to the satiety sensation that it produces; as a remedy for constipation, because it increases the faeces volume; as hypocholesterolemic agent, interfering in the transport of cholesterol and of bile acids and as hypoglycemic and hypoinsulinemic agent, probably, by delaying gastric emptying and slowering glucose delivery to the intestinal mucosa. To the beneficial properties of this fiber, several disadvantages can be added as the production of flatulence, abdominal pain, esophageal obstruction, lower gastrointestinal obstruction or even the possible modification of the bioavailability of other drugs. This paper reviews the main characteristics of glucomannan, as well as its properties, physiologic effects and therapeutic uses.
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PMID:[Glucomannan: properties and therapeutic applications]. 1498 41

Adipocyte dysfunction is strongly associated with the development of obesity and insulin resistance. It is accepted that the regulation of adipocytokine secretion or the adipocyte-specific gene expression is one of the most important targets for the prevention of obesity and amelioration of insulin sensitivity. In this study, we demonstrated that anthocyanins (cyanidin or cyanidin 3-glucoside) have the potency of a unique pharmacological function in isolated rat adipocytes. Treated adipocytes with anthocyanins enhanced adipocytokine (adiponectin and leptin) secretion and up-regulated the adipocyte specific gene expression without activation of PPARgamma in isolated rat adipocytes. The gene expression of adiponectin was also up-regulated in white adipose tissue in mice fed an anthocyanin supplemented diet. As one of the possible mechanisms, AMP-activated protein kinase activation would be associated with these changes, nevertheless, the AMP:ATP ratio was significantly decreased by administration of the anthocyanins. These data suggest that anthocyanins have a potency of unique therapeutic advantage and also have important implications for preventing obesity and diabetes.
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PMID:Anthocyanin enhances adipocytokine secretion and adipocyte-specific gene expression in isolated rat adipocytes. 1500 23

N-Acetylglucosaminyltransferase (GnT)-III catalyzes the attachment of an N-acetylglucosamine (GlcNAc) residue to mannose in beta(1-4) configuration in the region of N-glycans and forms a bisecting GlcNAc. To investigate the pathophysiological role of dysregulated glycosylation mediated by aberrantly expressed GnT-III, we generated transgenic mice hyperexpressing the human GnT-III in the liver by introducing human GnT-III cDNA under the control of mouse albumin enhancer/promoter. Total five transgenic founder mice (pGnTSVTpA-10, -14, -20, -25, and -51) expressed the human GnT-III in their livers and were characterized by molecular genetic means. The copy number of transgene integrated into the genome of these mice ranged between 1 and 3 copies per haploid genome. Northern and Western blot analyses showed that the transgene is specifically expressed in the liver but not in any other tissues tested. The triglyceride level in GnT-III transgenic mice was significantly decreased, however, no significant differences in the levels of glucose, cholesterol, or albumin were observed between transgenic and nontransgenic mice. Although glutamate oxaloacetic transaminase and glutamic pyruvic transaminase activities of transgenic mice were also higher than those of nontransgenic mice, no differences in total bililubin and total protein were observed between the two animal lines. Large amounts of apolipoprotein (Apo) A-I and Apo B were specifically detected in the intracellular liver of transgenic mice. The accumulation of Apo A-I in hepatocytes may be due to aberrant glycosylation, since glycosylated Apo A-I was not observed in transgenic mice. However, the accumulated Apo B was severely glycosylated. Therefore, it is suggested that highly expressed transgenic GnT-III allowed unknown target proteins to be glycosylated in large amounts, and the resulting target protein(s) disrupted in assembly formation of Apo A-I in the hepatocytes and cause a decrease in the release of lipoproteins and accumulations of Apo A-I and Apo B in the liver. The transgenic mice showed aberrant glycosylation by GnT-III, resulting in numerous lipid droplets in liver tissues and the obesity. These mice showed microvesicular fatty changes with abnormal lipid accumulation in the hepatocytes. Our study provides the basis for future analysis of the role of glycosylation in hepatic pathogenesis. In the transgenic mice, Apo A-I and Apo B were significantly increased compared with levels in nontransgenic liver tissues.
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PMID:Hyperexpression of N-acetylglucosaminyltransferase-III in liver tissues of transgenic mice causes fatty body and obesity through severe accumulation of Apo A-I and Apo B. 1513 Jul 79

We previously reported that mice lacking bombesin receptor subtype-3 (BRS-3) exhibit mild late-onset obesity and glucose intolerance [Nature 390 (1997) 160]. To examine the mechanism by which glucose intolerance is developed in these mice, we studied insulin release and proinsulin biosynthesis in isolated pancreatic islets and glucose uptake and facilitative glucose transporter (GLUT)-4 translocation in adipose tissues. Although islet insulin contents and the size and number of islets of Langerhans in BRS-3-deficient mice decreased, there was no difference in glucose-stimulated insulin release and proinsulin biosynthesis between BRS-3-deficient and wild-type control mice. In contrast, adipose tissues exhibited a marked difference: the uptake of [(14)C]2-deoxy-D-glucose by adipocytes isolated from BRS-3-deficient mice was not stimulated by 10(-7)M insulin addition, and membrane fractionation analysis showed that GLUT4 was barely detected in the fraction of plasma membrane in BRS-3-deficient mice in the presence of 10(-7)M insulin. Quantitative reverse transcription-PCR (RT-PCR) showed that mRNA levels of GLUT4, insulin receptor, insulin receptor substrate (IRS)-1 and IRS-2, syntaxin 4, SNAP23, and VAMP-2 in adipose tissues of BRS-3-deficient mice were unchanged compared with those in wild-type control mice. We concluded that impaired glucose metabolism observed in BRS-3-deficient mice was mainly caused by impaired GLUT4 translocation in adipocytes.
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PMID:Functions of pancreatic beta cells and adipocytes in bombesin receptor subtype-3-deficient mice. 1514 94

Obesity is associated with increased hepatic glycogen content. In vivo and in vitro data suggest that plasma free fatty acids (FFA) may cause this increase. In this study we investigated the effect of physiological plasma FFA levels on hepatic glycogen metabolism by studying intrahepatic glucose pathways in lean and obese subjects. Six lean and 6 obese males were studied twice during a 16- to 22-hour fast, once with and once without acipimox, an inhibitor of lipolysis. Intrahepatic glucose fluxes were measured by infusion of [2-(13C1)]glycerol, [1-(2H1)]galactose, and [U-(13C6)]glucose. Acetaminophen was administered as a glucuronate probe. In both lean and obese control studies, plasma FFA levels increased progressively, whereas acipimox completely suppressed plasma FFA levels for the whole study period. In lean males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). In lean males, neither glycogen synthesis, glycogen synthesis retained as glycogen, nor glycogen balance differed between control and acipimox studies. In obese males glycogenolysis did not change in the acipimox study, but decreased in the control study (P < .01). Glycogen synthesis did not change in either study. Glycogen synthesis retained as glycogen did not change in acipimox study, but increased in the control study (P = .03). Glycogen balance did not change in the acipimox study, but increased in the control study (P < .01). This study demonstrates that in obese males physiological levels of FFA contribute to the retention of hepatic glycogen during short-term fasting by inhibiting breakdown of glycogen and increasing glycogen synthesis retained as glycogen, whereas in lean males this effect was absent due to unaltered glycogen synthesis retained as glycogen.
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PMID:Free fatty acids increase hepatic glycogen content in obese males. 1525 82


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