scholarly journals Uric Acid Secretion from Adipose Tissue and Its Increase in Obesity

2013 ◽  
Vol 288 (38) ◽  
pp. 27138-27149 ◽  
Author(s):  
Yu Tsushima ◽  
Hitoshi Nishizawa ◽  
Yoshihiro Tochino ◽  
Hideaki Nakatsuji ◽  
Ryohei Sekimoto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Uric Acid ◽  
Acid Secretion ◽  
Acid Production ◽  
Culture Medium ◽  
Dependent Manner ◽  
Obese Mice ◽  
Subsequent Increase ◽  
Dose Dependent ◽  
Uric Acid Secretion

Obesity is often accompanied by hyperuricemia. However, purine metabolism in various tissues, especially regarding uric acid production, has not been fully elucidated. Here we report, using mouse models, that adipose tissue could produce and secrete uric acid through xanthine oxidoreductase (XOR) and that the production was enhanced in obesity. Plasma uric acid was elevated in obese mice and attenuated by administration of the XOR inhibitor febuxostat. Adipose tissue was one of major organs that had abundant expression and activities of XOR, and adipose tissues in obese mice had higher XOR activities than those in control mice. 3T3-L1 and mouse primary mature adipocytes produced and secreted uric acid into culture medium. The secretion was inhibited by febuxostat in a dose-dependent manner or by gene knockdown of XOR. Surgical ischemia in adipose tissue increased local uric acid production and secretion via XOR, with a subsequent increase in circulating uric acid levels. Uric acid secretion from whole adipose tissue was increased in obese mice, and uric acid secretion from 3T3-L1 adipocytes was increased under hypoxia. Our results suggest that purine catabolism in adipose tissue could be enhanced in obesity.

Angiopoietin-like 8 Improves Insulin Resistance and Attenuates Adipose Tissue Inflammation in Diet-Induced Obese Mice

2018 ◽  
Vol 128 (05) ◽  
pp. 290-296 ◽  
Author(s):  
Deng Luo ◽  
Xiaolin Chen ◽  
Wenqiang Yang ◽  
Wenzhuo Ran ◽  
Zhongyuan Wen
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Mrna Expression ◽  
M2 Macrophage ◽  
Dependent Manner ◽  
Adipose Tissue Inflammation ◽  
Obese Mice ◽  
Tissue Inflammation ◽  
M1 Macrophage ◽  
Dose Dependent

AbstractAngiopoietin-like 8 (ANGPTL8) is closely linked to obesity-associated metabolic diseases and insulin resistance. The aim of the current study was to investigate the ability of ANGPTL8 to reverse insulin resistance in obese mice. The administration of ANGPTL8 reduced weight gain and improved glucose tolerance in mice with diet-induced obesity. In addition, ANGPTL8 administration modified macrophage infiltration, reduced monocyte chemoattractant protein-1 (MCP-1) and interleukin-1β(IL-1β) levels, and increased adiponectin gene expression in inguinal white adipose tissue (iWAT). Moreover, the exposure of a cultured peritoneal macrophage line to ANGPTL8 reduced the mRNA expression of M1 macrophage markers (TNF-α and IL-1β) upon stimulation with lipopolysaccharides in a dose-dependent manner. By contrast, when incubated with IL-4, exposure of macrophages to ANGPTL8 increased the mRNA expression of M2 macrophage markers (Arg1 and Chi3l3) in a dose-dependent manner. Collectively, the results of the present study demonstrated that treatment with ANGPTL8 can attenuate adipose tissue inflammation through regulation of macrophage polarization, and thus, it could be useful for improving insulin resistance.

scholarly journals Preclinical Research on a Mixture of Red Ginseng and Licorice Extracts in the Treatment and Prevention of Obesity

Nutrients ◽  
2020 ◽  
Vol 12 (9) ◽  
pp. 2744
Author(s):  
Yulong Zheng ◽  
Eun-Hye Lee ◽  
Ji-Hyun Lee ◽  
Gyo In ◽  
JongHan Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipid Accumulation ◽  
Serum Triglyceride ◽  
The Body ◽  
Composition Analysis ◽  
Serum Triglyceride Level ◽  
Dependent Manner ◽  
Obese Mice ◽  
Ampk Pathway ◽  
Dose Dependent

The anti-obesity effects of RL (a 3:1 mixture of Panax ginseng saponin fractions and Glycyrrhiza glabra L. extracts) on 3T3-L1 adipocytes and C57BL/6J obese mice were evaluated at different concentrations. We investigated the anti-obesity effects of RL through lipid accumulation inhibition rate, serum lipid composition analysis, adipose tissue size, adipogenic transcription factors and AMPK pathway. RL inhibited the lipid accumulation of 3T3-L1 adipocytes in a dose-dependent manner at concentrations of 50–200 μg/mL without cytotoxicity (50–400 μg/mL). Oral administration of RL at the highest concentration (400 mg/kg/day) did not cause significant liver toxicity in high-fat diet-induced obese mice. RL stimulated adiponectin secretion in a dose-dependent manner and primarily mediates the AMPK pathway to inhibit triglyceride synthesis and attenuate adipocyte hypertrophy. RL significantly reduced weight in obese mice, but none of the body weight, adipose tissue weight, serum triglyceride level, and AMPK pathway activation degree showed any difference between dosing concentrations of 200 and 400 mg/kg/day. Therefore, 200 mg/kg/day of RL is the optimal preclinical concentration, which can be a reference concentration for conversion into a human clinical trial dose.

scholarly journals Nesfatin-1 inhibits gastric acid secretion via a central vagal mechanism in rats

2012 ◽  
Vol 303 (5) ◽  
pp. G570-G577 ◽  
Author(s):  
Ze-Feng Xia ◽  
Danielle M. Fritze ◽  
Ji-Yao Li ◽  
Biaoxin Chai ◽  
Chao Zhang ◽  
...  
Keyword(s):  
Food Intake ◽  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Acid Production ◽  
Dependent Manner ◽  
Central Administration ◽  
Inhibit Food Intake ◽  
Dose Dependent

Nesfatin-1, a novel hypothalamic peptide, inhibits nocturnal feeding behavior and gastrointestinal motility in rodents. The effects of nesfatin-1 on gastrointestinal secretory function, including gastric acid production, have not been evaluated. Nesfatin-1 was injected into the fourth intracerebral ventricle (4V) of chronically cannulated rats to identify a nesfatin dose sufficient to inhibit food intake. Nesfatin-1 (2 μg) inhibited dark-phase food intake, in a dose-dependent fashion, for >3 h. Gastric acid production was evaluated in urethane-anesthetized rats. Nesfatin-1 (2 μg) was introduced via the 4V following endocrine stimulation of gastric acid secretion by pentagastrin (2 μg·kg−1·h−1 iv), vagal stimulation with 2-deoxy-d-glucose (200 mg/kg sc), or no stimulus. Gastric secretions were collected via gastric cannula and neutralized by titration to determine acid content. Nesfatin-1 did not affect basal and pentagastrin-stimulated gastric acid secretion, whereas 2-deoxy-d-glucose-stimulated gastric acid production was inhibited by nesfatin-1 in a dose-dependent manner. c-Fos immunofluorescence in brain sections was used to evaluate in vivo neuronal activation by nesfatin-1 administered via the 4V. Nesfatin-1 caused activation of efferent vagal neurons, as evidenced by a 16-fold increase in the mean number of c-Fos-positive neurons in the dorsal motor nucleus of the vagus (DMNV) in nesfatin-1-treated animals vs. controls ( P < 0.01). Finally, nesfatin-induced Ca2+ signaling was evaluated in primary cultured DMNV neurons from neonatal rats. Nesfatin-1 caused dose-dependent Ca2+ increments in 95% of cultured DMNV neurons. These studies demonstrate that central administration of nesfatin-1, at doses sufficient to inhibit food intake, results in inhibition of vagally stimulated secretion of gastric acid. Nesfatin-1 activates DMNV efferent vagal neurons in vivo and triggers Ca2+ signaling in cultured DMNV neurons.

Papaya shoot tip associated endophytic bacteria isolated from in vitro cultures and host–endophyte interaction in vitro and in vivo

2007 ◽  
Vol 53 (3) ◽  
pp. 380-390 ◽  
Author(s):  
Pious Thomas ◽  
Sima Kumari ◽  
Ganiga K. Swarna ◽  
T.K.S. Gowda
Keyword(s):  
Culture Medium ◽  
Carica Papaya ◽  
In Vitro Cultures ◽  
Dependent Manner ◽  
16S Rdna Sequence ◽  
16S Rdna Sequence Analysis ◽  
Single Organism ◽  
Dose Dependent

Fourteen distinct bacterial clones were isolated from surface-sterilized shoot tips (~1 cm) of papaya (Carica papaya L. ‘Surya’) planted on Murashige and Skoog (MS)-based papaya culture medium (23/50 nos.) during the 2–4 week period following in vitro culturing. These isolates were ascribed to six Gram-negative genera, namely Pantoea ( P. ananatis ), Enterobacter ( E. cloacae ), Brevundimonas ( B. aurantiaca ), Sphingomonas , Methylobacterium ( M. rhodesianum ), and Agrobacterium ( A. tumefaciens ) or two Gram-positive genera, Microbacterium ( M. esteraromaticum ) and Bacillus ( B. benzoevorans ) based on 16S rDNA sequence analysis. Pantoea ananatis was the most frequently isolated organism (70% of the cultures) followed by B. benzoevorans (13%), while others were isolated from single stocks. Bacteria-harboring in vitro cultures often showed a single organism. Pantoea, Enterobacter, and Agrobacterium spp. grew actively on MS-based normal papaya medium, while Microbacterium, Brevundimonas, Bacillus, Sphingomonas, and Methylobacterium spp. failed to grow in the absence of host tissue. Supplying MS medium with tissue extract enhanced the growth of all the organisms in a dose-dependent manner, indicating reliance of the endophyte on its host. Inoculation of papaya seeds with the endophytes (20 h at OD550 = 0.5) led to delayed germination or slow seedling growth initially. However, the inhibition was overcome by 3 months and the seedlings inoculated with Pantoea, Microbacterium, or Sphingomonas spp. displayed significantly better root and shoot growths.

scholarly journals Glyoxalase I is a novel nitric-oxide-responsive protein

1999 ◽  
Vol 344 (3) ◽  
pp. 837-844 ◽  
Author(s):  
Atsushi MITSUMOTO ◽  
Kwi-Ryeon KIM ◽  
Genichiro OSHIMA ◽  
Manabu KUNIMOTO ◽  
Katsuya OKAWA ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Culture Medium ◽  
Molecular Mechanisms ◽  
Peptide Mapping ◽  
Glyoxalase I ◽  
Dependent Manner ◽  
Human Endothelial Cells ◽  
Native Form ◽  
No Donors ◽  
Dose Dependent

To clarify the molecular mechanisms of nitric oxide (NO) signalling, we examined the NO-responsive proteins in cultured human endothelial cells by two-dimensional (2D) PAGE. Levels of two proteins [NO-responsive proteins (NORPs)] with different pI values responded to NO donors. One NORP (pI 5.2) appeared in response to NO, whereas another (pI 5.0) disappeared. These proteins were identified as a native form and a modified form of human glyoxalase I (Glox I; EC 4.4.1.5) by peptide mapping, microsequencing and correlation between the activity and the isoelectric shift. Glox I lost activity in response to NO, and all NO donors tested inhibited its activity in a dose-dependent manner. Activity and normal electrophoretic mobility were restored by dithiothreitol and by the removal of sources of NO from the culture medium. Glox I was selectively inactivated by NO; compounds that induce oxidative stress (H2O2, paraquat and arsenite) failed to inhibit this enzyme. Our results suggest that NO oxidatively modifies Glox I and reversibly inhibits the enzyme's activity. The inactivation of Glox I by NO was more effective than that of glyceraldehyde-3-phosphate dehydrogenase (G3PDH), another NO-sensitive enzyme. Thus Glox I seems to be a novel NO-responsive protein that is more sensitive to NO than G3PDH.

scholarly journals Regulation of steroidogenesis in fetal bovine ovaries: differential effects of LH and FSH

2016 ◽  
Vol 57 (4) ◽  
pp. 275-286 ◽  
Author(s):  
J J Allen ◽  
S L Herrick ◽  
J E Fortune
Keyword(s):  
Culture Medium ◽  
Fetal Life ◽  
Dependent Manner ◽  
Ovarian Steroid ◽  
Steroid Production ◽  
Steroid Synthesis ◽  
Primordial Follicles ◽  
Preovulatory Follicles ◽  
Fetal Bovine ◽  
Dose Dependent

In cattle, primordial follicles form before birth. Fetal ovarian capacity to produce progesterone and estradiol is high before follicle formation begins and decreases around the time follicles first appear (around 90 days of gestation). However, mechanisms that regulate steroid production during this time remain unclear. We hypothesized that LH stimulates progesterone and androgen production and that FSH stimulates aromatization of androgens to estradiol. To test this, we cultured pieces from fetal bovine ovaries for 10 days without or with exogenous hormones and then measured the accumulation of steroids in the culture medium by RIA. LH (100 ng/mL) alone increased the accumulation of progesterone, androstenedione, testosterone and estradiol. FSH (100 ng/mL) alone increased both progesterone and estradiol accumulation, but had no effect on androgens. Exogenous testosterone (0.5 µM) alone greatly increased estradiol accumulation and the combination of testosterone + FSH, but not testosterone + LH, increased estradiol relative to testosterone alone. Interestingly, exogenous testosterone and estradiol decreased progesterone accumulation in a dose-dependent manner. Because the highest dose of estradiol (0.5 µM) decreased progesterone accumulation, but increased both pregnenolone and androstenedione in the same cultures, endogenous estradiol may be a paracrine regulator of steroid synthesis. Together, these results confirm our initial hypotheses and indicate that LH stimulates androgen production in fetal bovine ovaries via the Δ5 pathway, whereas FSH stimulates aromatization of androgens to estradiol. These results are consistent with the two-cell, two-gonadotropin model of estradiol production by bovine preovulatory follicles, which suggests that the mechanisms regulating ovarian steroid production are established during fetal life.

scholarly journals Intravenous infusions of glucose stimulate key lipogenic enzymes in adipose tissue of dairy cows in a dose-dependent manner

2013 ◽  
Vol 96 (7) ◽  
pp. 4299-4309 ◽  
Author(s):  
Mirja Carra ◽  
Bahaa Al-Trad ◽  
Gregory B. Penner ◽  
Thomas Wittek ◽  
Gotthold Gäbel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Dairy Cows ◽  
Dependent Manner ◽  
Lipogenic Enzymes ◽  
Intravenous Infusions ◽  
Dose Dependent

Effect of catecholamines on somatostatin secretion by isolated perfused rat stomach

1981 ◽  
Vol 240 (3) ◽  
pp. E274-E278
Author(s):  
Y. Goto ◽  
M. Berelowitz ◽  
L. A. Frohman
Keyword(s):  
Acid Secretion ◽  
Gastric Acid Secretion ◽  
Gastric Acid ◽  
Inhibitory Effect ◽  
Dependent Manner ◽  
Rat Stomach ◽  
Beta Adrenergic ◽  
Somatostatin Secretion ◽  
Adrenergic Mechanism ◽  
Dose Dependent

The secretion of somatostatin-like immunoreactivity (SRIF-LI) by the isolated perfused rat stomach was studied in response to stimulation by catecholamines. Gastric SRIF-LI secretion was significantly stimulated in a dose-dependent manner by norepinephrine at 10(-6) and 10(-8) M, and the effect of norepinephrine (10(-8) M) was attenuated by the addition of propranolol (10(-6) M) but not of phentolamine (10(-6) M). SRIF-LI secretion was also stimulated by dopamine at concentrations of 10(-4) and 10(-6) M but not at 10(-8) M. The effect of dopamine (10(-6) M) was not altered by the addition of haloperidol (10(-4) to 10(-7)) or metoclopramide (10(-4) M), and bromocriptine (10(-6) M) was without effect on SRIF-LI secretion. These results suggest that gastric SRIF-LI secretion is stimulated by a beta-adrenergic mechanism and raise the possibility that gastric somatostatin contributes to the inhibitory effect of norepinephrine on gastric acid secretion.

scholarly journals Naringenin Inhibits Adipogenesis and Reduces Insulin Sensitivity and Adiponectin Expression in Adipocytes

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Allison J. Richard ◽  
Zhaleh Amini-Vaughan ◽  
David M. Ribnicky ◽  
Jacqueline M. Stephens
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Cell Function ◽  
Negative Impact ◽  
Time Frame ◽  
Dependent Manner ◽  
Fat Cell ◽  
The Metabolic Syndrome ◽  
Citrus Flavonoids ◽  
Dose Dependent

Adipose tissue development and function are widely studied to examine the relationship between obesity and the metabolic syndrome. It is well documented that the inability of adipose tissue to properly increase its lipid storage capacity during the obese state can lead to metabolic dysfunction. In a blind screen of 425 botanicals, we identified naringenin as an inhibitor of adipocyte differentiation. Naringenin is one of the most abundant citrus flavonoids, and recent studies have demonstrated antihyperlipidemic capabilities. These studies have largely focused on the effects of naringenin on the liver. Our biochemical studies clearly demonstrate that naringenin inhibits adipogenesis and impairs mature fat cell function. Naringenin specifically inhibited adipogenesis in a dose-dependent fashion as judged by examining lipid accumulation and induction of adipocyte marker protein expression. In mature 3T3-L1 adipocytes, naringenin reduced the ability of insulin to induce IRS-1 tyrosine phosphorylation and substantially inhibited insulin-stimulated glucose uptake in a dose-dependent manner and over a time frame of 1.5 to 24 hours. Exposure to naringenin also inhibited adiponectin protein expression in mature murine and human adipocytes. Our studies have revealed that naringenin may have a negative impact on adipocyte-related diseases by limiting differentiation of preadipocytes, by significantly inducing insulin resistance, and by decreasing adiponectin expression in mature fat cells.

Sign in / Sign up

Export Citation Format

Share Document