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

Anthocyanins are red, purple, or blue plant water-soluble pigments. In the past two decades, anthocyanins have received extensive studies for their anti-oxidative, anti-inflammatory, anti-cancer, anti-obesity, anti-diabetic, and cardioprotective properties. In the present study, anthocyanin biosynthetic enzymes from different plant species were characterized and employed for pathway construction leading from inexpensive precursors such as flavanones and flavan-3-ols to anthocyanins in Escherichia coli. The recombinant E. coli cells successfully achieved milligram level production of two anthocyanins, pelargonidin 3-O-glucoside (0.98 mg/L) and cyanidin 3-O-gluside (2.07 mg/L) from their respective flavanone precursors naringenin and eriodictyol. Cyanidin 3-O-glucoside was produced at even higher yields (16.1 mg/L) from its flavan-3-ol, (+)-catechin precursor. Further studies demonstrated that availability of the glucosyl donor, UDP-glucose, was the key metabolic limitation, while product instability at normal pH was also identified as a barrier for production improvement. Therefore, various optimization strategies were employed for enhancing the homogenous synthesis of UDP-glucose in the host cells while at the same time stabilizing the final anthocyanin product. Such optimizations included culture medium pH adjustment, the creation of fusion proteins and the rational manipulation of E. coli metabolic network for improving the intracellular UDP-glucose metabolic pool. As a result, production of pelargonidin 3-O-glucoside at 78.9 mg/L and cyanidin 3-O-glucoside at 70.7 mg/L was achieved from their precursor flavan-3-ols without supplementation with extracellular UDP-glucose. These results demonstrate the efficient production of the core anthocyanins for the first time and open the possibility for their commercialization for pharmaceutical and nutraceutical applications.
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PMID:High-yield anthocyanin biosynthesis in engineered Escherichia coli. 1802 53

Obstructive sleep apnoea (OSA) and type 2 diabetes frequently co-exist and potentially interact haemodynamically and metabolically. However, the confounding effects of obesity have obscured the examination of any independent or interactive effects of the hypoxic stress of OSA and the hyperglycaemia of type 2 diabetes on haemodynamic and metabolic outcomes. We have developed a chronically catheterized, unhandled, lean murine model to examine the effects of intermittent hypoxic (IH) exposure and exogenous glucose infusion on the diurnal pattern of arterial blood pressure and blood glucose, as well as pancreatic beta-cell growth and function. Four experimental groups of adult male C57BL/J mice were exposed to 80 h of (1) either IH (nadir of inspired oxygen 5-6% at 60 cycles h(-1) for 12 h during light period) or intermittent air (IA; control) and (2) continuous infusion of either 50% dextrose or saline (control). IH exposure during saline infusion caused a sustained increase in arterial blood pressure of 10 mmHg (P < 0.0001), reversed the normal diurnal rhythm of blood glucose (P < 0.03), doubled corticosterone levels (P < 0.0001), and increased replication of pancreatic beta-cells from 1.5 +/- 0.3 to 4.0 +/- 0.8% bromodeoxyuridine (BrdU)-positive) beta-cells. The combined stimulus of IH exposure and glucose infusion attenuated the hypertension, exacerbated the reversed diurnal glucose rhythm, and produced the highest rates of apoptosis in beta-cells, without any additive effects on beta-cell replication. We conclude that, in contrast to the development of sustained hypertension, IH impaired glucose homeostasis only during periods of hypoxic exposure. IH acted as a stimulus to pancreatic beta-cell replication, but the presence of hyperglycaemia may increase the hypoxic susceptibility of beta-cells. This model will provide a basis for future mechanistic studies as well as assessing the metabolic impact of common comorbities in OSA, including obesity, insulin resistance and type 2 diabetes.
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PMID:Intermittent hypoxia reverses the diurnal glucose rhythm and causes pancreatic beta-cell replication in mice. 1803 15

The endogenous cannabinoid system plays a role in the regulation of energy homeostasis acting through central pathways, and its dysregulation may be implicated in the pathogenesis of obesity. Recent evidence is accumulating showing that the endogenous cannabinoid system is also present in peripheral tissues. The aim of this work was to investigate the effect of cannabinoids upon the intestinal absorption of glucose. For this, we investigated the effect of some cannabinoid receptor agonists and antagonists upon the apical uptake of 3H-2-deoxy-D-glucose by the human intestinal epithelial Caco-2 cells. Uptake of a low concentration of 3H-2-deoxy-D-glucose (1 micromol/l) was both cytochalasin B- and phloridzin-sensitive. The maximal inhibition obtained with each of these inhibitors was 50%, and their effect was not cumulative. On the other hand, uptake of a high concentration of 3H-2-deoxy-D-glucose (20 mmol/l) was partially inhibited by cytochalasin B (+/-20%) and phloridzin had no effect. We verified that neither the cannabinoid receptor agonists [tetrahydrocannabinol (1-10 micromol/l), anandamide (0.1-10 micromol/l) and CP 55,940 (5 nmol/l to 1 micromol/l)], nor the specific CB1 and CB2 antagonists [AM251 (10-500 nmol/l) and AM630 (50 nmol/l to 1 micromol/l), respectively] had a significant effect upon 3H-2-deoxy-D-glucose uptake by Caco-2 cells. This was true for both the uptake of a low (1 micromol/l) and of a high (20 mmol/l) concentration of 3H-2-deoxy-D-glucose. From these results, we may hypothesize that cannabinoids do not interfere with the intestinal GLUT2-mediated apical uptake of glucose.
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PMID:Lack of a significant effect of cannabinoids upon the uptake of 2-deoxy-D-glucose by Caco-2 cells. 1843 Oct 74

Anthocyanins are among the most common flavonoids in the human diet. In spite of their very low bioavailability, anthocyanins are indicated as active in preventing the progress of cardiovascular and neurodegenerative diseases, obesity, inflammation, and cancer. Any piece of knowledge concerning absorption, tissue distribution, metabolism, and excretion of dietary anthocyanins is expected to help understanding the apparent paradox between their low concentrations in cells and their bioactivity. The aim of this work was to investigate the renal uptake of dietary anthocyanins and the underlying molecular mechanism. A solution containing anthocyanins extracted from grape (Vitis vinifera) was introduced into the isolated stomach of anesthetized rats; after both 10 and 30 min, plasma, liver, and kidney were analyzed for their anthocyanin contents. While anthocyanins in the liver were at apparent equilibrium with plasma both after 10 and 30 min, kidney anthocyanins were 3- and 2.3-fold higher than in plasma, after 10 and 30 min, respectively. Since the transport activity of the bilitranslocase in kidney basolateral membrane vesicles was competitively inhibited by malvidin 3-glucoside (K(i) = 4.8 +/- 0.2 microM), the anthocyanin uptake from blood into kidney tubular cells is likely to be mediated by the kidney isoform of this organic anion membrane transporter.
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PMID:Uptake of grape anthocyanins into the rat kidney and the involvement of bilitranslocase. 1865 7

sCD40L is a proatherogenic cytokine, part of the tumor necrosis factor (TNF) superfamily and consistently associated with obesity, diabetes, and increased cardiovascular risk. Although the role of sCD40L in the onset/progression of cardiovascular complications of dysmetabolic diseases may be modulated by acute and/or chronic fluctuations of plasma insulin and glucose, very little has been done to clarify this interaction. The kinetic profile of sCD40L (and, in an exploratory manner, of several immunomodulatory factors), were measured during hyperglycemia and euglycemic-hyperinsulinemia in a group of 10 healthy young males (26.8 +/- 1.4 years). After an overnight fast, intravenous (iv) catheters were placed in antecubital veins of both arms for blood drawing and dextrose/insulin iv infusions. Procedures lasted 240 minutes including baseline (t = 0-60), hyperglycemia (t = 60-150; plasma glucose approximately 220 mg/dL via iv dextrose infusion), and euglycemic-hyperinsulinemia (t = 150-240; glucose infusion continued to clamp glycemic levels between 80 and 110 mg/dL; constant insulin infusion at 1.5 mU/kg/minute).Plasma for cytokine assays was sampled at 12 separate time-points. Plasma levels of sCD40L were significantly reduced (P < 0.01) during hyperglycemia and euglycemic-hyperinsulinemia, paralleling the kinetic profiles of free fatty acids and ketone bodies. This pattern was also observed in other immunomodulatory factors (notably cortisol and epidermal growth factor), while (interleukin [IL]-1alpha, IL-4, IL-6, IL-9, IL-10, TNF-alpha, Eotaxin) did not change significantly. Significant reductions of the proatherogenic cytokine sCD40L were observed during endogenous and exogenous hyperinsulinemia, independent of prevailing glucose concentration, in young healthy males. Our data suggest a mechanism by which correct insulin action may exert a beneficial protective role against inflammation, independent of its immediate glucose-lowering effect.
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PMID:Acute suppression of circulating sCD40L during hyperglycemia and euglycemic-hyperinsulinemia in healthy young males. 1879 14

Obesity has been associated with a higher risk for impaired cognitive function, which most likely reflects associated medical complications (i.e., cerebrovascular pathology). However, there is also evidence that in healthy individuals excess weight may adversely affect cognition (executive function, attention, and memory). Here, we measured regional brain glucose metabolism (using positron emission tomography (PET) and 2-deoxy-2[(18)F]fluoro-D-glucose (FDG)) to assess the relationship between BMI and brain metabolism (marker of brain function) in 21 healthy controls (BMI range 19-37 kg/m(2)) studied during baseline (no stimulation) and during cognitive stimulation (numerical calculations). Statistical parametric mapping (SPM) revealed a significant negative correlation between BMI and metabolic activity in prefrontal cortex (Brodmann areas 8, 9, 10, 11, 44) and cingulate gyrus (Brodmann area 32) but not in other regions. Moreover, baseline metabolism in these prefrontal regions was positively associated with performance on tests of memory (California Verbal Learning Test) and executive function (Stroop Interference and Symbol Digit Modality tests). In contrast, the regional brain changes during cognitive stimulation were not associated with BMI nor with neuropsychological performance. The observed association between higher BMI and lower baseline prefrontal metabolism may underlie the impaired performance reported in healthy obese individuals on some cognitive tests of executive function. On the other hand, the lack of an association between BMI and brain metabolic activation during cognitive stimulation indicates that BMI does not influence brain glucose utilization during cognitive performance. These results further highlight the urgency to institute public health interventions to prevent obesity.
Obesity (Silver Spring) 2009 Jan
PMID:Inverse association between BMI and prefrontal metabolic activity in healthy adults. 1894 65

Obesity, particularly visceral adiposity, is an established risk factor for colorectal cancer (CRC) and this is thought to result, at least in part, from insulin resistance and chronic hyperinsulinemia that may be mediated by adipokines. Serum levels of adiponectin, the most abundant protein secreted from adipocytes, are decreased in obesity and are inversely associated with insulin resistance and hyperinsulinemia. The objective of this study was to determine whether elevated circulating adiponectin plays a role in colon carcinogenesis using adiponectin transgenic (AdTg) mice that have 2-3-fold elevated circulating adiponectin but similar body weights as wildtype (WT) littermates used as controls. Eight-week old male and female AdTg and WT mice were treated with 4 weekly injections of the colon-specific carcinogen azoxymethane (AOM). One week following the last dose of AOM, all mice were placed on a high-fat diet and killed 24 weeks later, at 36 weeks of age, for the analysis of colon tumors. Glucose tolerance tests (GTT) were performed by injecting 2g/kg dextrose or 1.25-1.5 g/kg dextrose into all 12-week and 32-35-week-old mice respectively, and measuring blood from the tail vein 15, 30, 60 and 120 min following glucose administration. There were no significant differences in colon tumor incidence, number or size between AdTg and WT mice of either sex. AdTg mice of both sexes displayed resistance to diet-induced decreases in insulin sensitivity. Our results show that constitutively elevated levels of circulating adiponectin in AdTg mice do not confer protection against the development of colon tumors.
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PMID:Elevated circulating adiponectin and elevated insulin sensitivity in adiponectin transgenic mice are not associated with reduced susceptibility to colon carcinogenesis. 1954 61

Although impaired inhibitory control is linked to a broad spectrum of health problems, including obesity, the brain mechanism(s) underlying voluntary control of hunger are not well understood. We assessed the brain circuits involved in voluntary inhibition of hunger during food stimulation in 23 fasted men and women using PET and 2-deoxy-2[(18)F]fluoro-D-glucose ((18)FDG). In men, but not in women, food stimulation with inhibition significantly decreased activation in amygdala, hippocampus, insula, orbitofrontal cortex, and striatum, which are regions involved in emotional regulation, conditioning, and motivation. The suppressed activation of the orbitofrontal cortex with inhibition in men was associated with decreases in self-reports of hunger, which corroborates the involvement of this region in processing the conscious awareness of the drive to eat. This finding suggests a mechanism by which cognitive inhibition decreases the desire for food and implicates lower ability to suppress hunger in women as a contributing factor to gender differences in obesity.
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PMID:Evidence of gender differences in the ability to inhibit brain activation elicited by food stimulation. 1932 32

Adipose tissue macrophages (ATMs) play a critical role in obesity-induced inflammation and insulin resistance. Distinct subtypes of ATMs have been identified that differentially express macrophage galactose-type C-type lectin 1 (MGL1/CD301), a marker of alternatively activated macrophages. To evaluate if MGL1 is required for the anti-inflammatory function of resident (type 2) MGL1(+) ATMs, we examined the effects of diet-induced obesity (DIO) on inflammation and metabolism in Mgl1(-/-) mice. We found that Mgl1 is not required for the trafficking of type 2 ATMs to adipose tissue. Surprisingly, obese Mgl1(-/-) mice were protected from glucose intolerance, insulin resistance, and steatosis despite having more visceral fat. This protection was caused by a significant decrease in inflammatory (type 1) CD11c(+) ATMs in the visceral adipose tissue of Mgl1(-/-) mice. MGL1 was expressed specifically in 7/4(hi) inflammatory monocytes in the blood and obese Mgl1(-/-) mice had lower levels of 7/4(hi) monocytes. Mgl1(-/-) monocytes had decreased half-life after adoptive transfer and demonstrated decreased adhesion to adipocytes indicating a role for MGL1 in the regulation of monocyte function. This study identifies MGL1 as a novel regulator of inflammatory monocyte trafficking to adipose tissue in response to DIO.
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PMID:MGL1 promotes adipose tissue inflammation and insulin resistance by regulating 7/4hi monocytes in obesity. 1999 56

Hyperinsulinemia increases sympathetic nerve activity (SNA) and has been linked to cardiovascular morbidity in obesity. The rostral ventrolateral medulla (RVLM) plays a key role in the regulation of SNA and arterial blood pressure (ABP). Many sympathoexcitatory responses are mediated by glutamatergic receptor activation within the RVLM, and both the central renin-angiotensin and melanocortin systems are implicated in the sympathoexcitatory response to hyperinsulinemia. Therefore, we hypothesized that one or more of these neurotransmitters in the RVLM mediate the sympathoexcitatory response to insulin. Hyperinsulinemic-euglycemic clamps were performed in alpha-chloralose anesthetized, male Sprague-Dawley rats by infusion of insulin (3.75 mU/kg per minute, IV) and 50% dextrose solution for 120 minutes. Physiological increases in plasma insulin elevated lumbar SNA, with no change in renal SNA, ABP, or blood glucose. Microinjection of the ionotropic glutamate receptor antagonist kynurenic acid into the RVLM significantly reduced lumbar SNA and ABP. Selective blockade of NMDA but not non-NMDA glutamate receptors resulted in similar reductions of lumbar SNA. In marked contrast, microinjection of the angiotensin II type 1 receptor antagonist losartan or the melanocortin 3/4 antagonist SHU9119 had no effect on lumbar SNA or ABP. Western blot analysis showed that insulin receptor expression is significantly lower in the RVLM than the hypothalamus, and direct microinjection of insulin into the RVLM did not significantly increase lumbar SNA. These findings suggest that hyperinsulinemia increases lumbar SNA by activation of a glutamatergic NMDA-dependent projection to the RVLM.
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PMID:Glutamatergic receptor activation in the rostral ventrolateral medulla mediates the sympathoexcitatory response to hyperinsulinemia. 2006 45


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