scholarly journals Novel Facet of an Old Dietary Molecule? Direct Influence of Caffeine on Glucose and Biogenic Amine Handling by Human Adipocytes

Molecules ◽  
2021 ◽  
Vol 26 (13) ◽  
pp. 3831
Author(s):  
Wiem Haj Ahmed ◽  
Nathalie Boulet ◽  
Anaïs Briot ◽  
Barry J. Ryan ◽  
Gemma K. Kinsella ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Amine Oxidase ◽  
Human Adipose Tissue ◽  
Lipid Solubility ◽  
Human Adipocytes ◽  
Peripheral Tissues ◽  
Amine Oxidation ◽  
High Lipid ◽  
The Central Nervous System ◽  
High Lipid Solubility

Caffeine is a plant alkaloid present in food and beverages consumed worldwide. It has high lipid solubility with recognized actions in the central nervous system and in peripheral tissues, notably the adipose depots. However, the literature is scant regarding caffeine’s influence on adipocyte functions other than lipolysis, such as glucose incorporation into lipids (lipogenesis) and amine oxidation. The objective of this study was to explore the direct effects of caffeine and of isobutylmethylxanthine (IBMX) on these adipocyte functions. Glucose transport into fat cells freshly isolated from mice, rats, or humans was monitored by determining [3H]-2-deoxyglucose (2-DG) uptake, while the incorporation of radiolabeled glucose into cell lipids was used as an index of lipogenic activity. Oxidation of benzylamine by primary amine oxidase (PrAO) was inhibited by increasing doses of caffeine in human adipose tissue preparations with an inhibition constant (Ki) in the millimolar range. Caffeine inhibited basal and insulin-stimulated glucose transport as well as lipogenesis in rodent adipose cells. The antilipogenic action of caffeine was also observed in adipocytes from mice genetically invalidated for PrAO activity, indicating that PrAO activity was not required for lipogenesis inhibition. These caffeine inhibitory properties were extended to human adipocytes: relative to basal 2-DG uptake, set at 1.0 ± 0.2 for 6 individuals, 0.1 mM caffeine tended to reduce uptake to 0.83 ± 0.08. Insulin increased uptake by 3.86 ± 1.11 fold when tested alone at 100 nM, and by 3.21 ± 0.80 when combined with caffeine. Our results reinforce the recommendation of caffeine’s potential in the treatment or prevention of obesity complications.

A Case of Acute Poisoning with Fenitrothion (Sumithion)

1987 ◽  
Vol 6 (5) ◽  
pp. 403-406 ◽  
Author(s):  
M. Yoshida ◽  
E. Shimada ◽  
S. Yamanaka ◽  
H. Aoyama ◽  
Y. Yamamura ◽  
...  
Keyword(s):  
Respiratory Insufficiency ◽  
Attempted Suicide ◽  
Clinical Symptoms ◽  
Acute Poisoning ◽  
Lipid Solubility ◽  
Fat Tissue ◽  
High Lipid ◽  
High Lipid Solubility

A 56-year-old male attempted suicide by ingestion of about 60 ml of 50% fenitrothion (Sumithion) emulsion. Five hours later, combined hemoperfusion and hemodialysis (HP-HD) treatment was performed for 60 min and consequently the toxic symptoms improved gradually. However, cholinergic symptoms recurred 4 days after ingestion. Although HP-HD was immediately performed for 180 min, it had no effect on the clinical symptoms. He died of respiratory insufficiency 6 days after the ingestion of fenitrothion. Fenitrothion concentration in the organs and tissues showed the highest values in the fat tissue, followed in decreasing order by the pancreas, muscle, lung and brain. The results indicate that fenitrothion has high lipid solubility and deposits in the fat tissue. Furthermore, we believe that when HP-HD therapy is used in the treatment of acute insecticide poisoning it is important that it be performed continuously and in as early a stage as possible.

Organochlorine Pesticides

2019 ◽  
pp. 41-63
Author(s):  
Garima Harit
Keyword(s):  
Water Pollution ◽  
Organochlorine Pesticides ◽  
Aquatic Environment ◽  
Lipid Solubility ◽  
Major Contributor ◽  
Human Beings ◽  
Freshwater Organisms ◽  
High Lipid ◽  
High Lipid Solubility ◽  
Great Danger

Indiscriminate use of different pesticides in agriculture has increased over the years, especially in the developing countries. This influences the aquatic environment to a great extent. This also poses a great danger to freshwater organisms, including fish, which constitute a major share in the aquatic environment and contribute to the economy of the nation. Water pollution is posing intricate problems that need immediate redress. Organo-chlorine pesticides (OCPs) are a major contributor to aquatic pollution and are amongst the most serious global contaminants. In addition, organochlorine pesticides have a tendency to accumulate in aquatic biota; they also undergo food chain amplification. Lipophilic pollutants are chemically very stable and resistant to microbial, photochemical, chemical, and thermal degradation. The chemical stability of these compounds, their high lipid solubility, and their toxicity to human beings and animals has led government and researchers to feel concerned about their presence in the environment.

Rapid passage of organic anions into human red cells

1964 ◽  
Vol 207 (2) ◽  
pp. 503-508 ◽  
Author(s):  
Lewis S. Schanker ◽  
Jean M. Johnson ◽  
John J. Jeffrey
Keyword(s):  
Cell Membrane ◽  
Organic Anions ◽  
Sulfanilic Acid ◽  
Lipid Solubility ◽  
Phenol Red ◽  
Sulfosalicylic Acid ◽  
High Lipid ◽  
Intracellular Binding ◽  
The Times ◽  
High Lipid Solubility

The rates at which organic acids penetrate the human red cell suspended in Tyrode's solution are roughly related to the lipid-to-water partition coefficients of the compounds measured at pH 7.4 using chloroform as a lipidlike solvent. Phenol, sulfadiazine, sulfathiazole, 5-nitrosalicylic acid, p-aminobenzoic acid, and salicylic acid, compounds of relatively high lipid solubility, become equilibrated between the cells and suspending medium in less than 5 min. Phenol red, sulfosalicylic acid, sulfanilic acid, hippuric acid, and p-aminohippuric acid, compounds of lower lipid solubility, become equilibrated more slowly, the times ranging from 1 to more than 7 hr. Measurements of the intracellular binding of phenol red and sulfosalicylic acid indicate that the unbound anions are distributed across the cell membrane according to a Donnan equilibrium. Organic anions enter the cell much more rapidly than do organic cations of a similar low lipid solubility. The preferential permeability toward anions is considered in terms of various models of the cell membrane, and a mechanism for anion penetration is suggested.

Radioactively iodinated cyclo(His-Pro) crosses the blood-brain barrier and reverses ethanol-induced narcosis

1993 ◽  
Vol 264 (5) ◽  
pp. E723-E729 ◽  
Author(s):  
W. A. Banks ◽  
A. J. Kastin ◽  
V. Akerstrom ◽  
J. B. Jaspan
Keyword(s):  
Blood Brain Barrier ◽  
Serum Proteins ◽  
Intraperitoneal Administration ◽  
Brain Barrier ◽  
Lipid Solubility ◽  
Peripheral Tissues ◽  
Blood Brain ◽  
Other Substances ◽  
High Lipid Solubility ◽  
The Brain

Cyclo(His-Pro) (cHP) is a peptide widely distributed in the central nervous system (CNS) and peripheral tissues that can affect brain function after either peripheral or CNS administration. This suggests that cHP may be a neuromodulator capable of crossing the blood-brain barrier (BBB). We, therefore, studied the ability of radioactively labeled cHP (I-cHP) to cross the BBB. We found that I-cHP can cross the BBB in either the direction of blood to brain or brain to blood by nonsaturable mechanisms. The rate of entry of I-cHP into the CNS was low in comparison with other peptides, especially considering its relatively low molecular weight and high lipid solubility. However, this slow entry was offset by a long half-life in blood and extreme enzymatic resistance, allowing cHP to accumulate in the CNS. This accumulation was sufficient to allow intravenous cHP to reverse ethanol-induced narcosis, an effect mediated through the CNS. The rate of entry of I-cHP was resistant to conditions that alter the passage of some other substances across the BBB or that have been shown to affect cHP metabolism such as aging, diabetes, and pretreatment with aluminum. Entry of cHP into the brain was not retarded by binding to serum proteins. Significant amounts of I-cHP entered the serum, brain, and other tissues after intraperitoneal administration, the route used in many studies of cHP. Taken together, these results show that cHP is a highly stable peptide that, after intravenous injection, slowly enters the brain by a nonsaturable mechanism in amounts large enough to affect such aspects of the CNS as ethanol-induced narcosis.

scholarly journals Opipramol Inhibits Lipolysis in Human Adipocytes without Altering Glucose Uptake and Differently from Antipsychotic and Antidepressant Drugs with Adverse Effects on Body Weight Control

2020 ◽  
Vol 13 (3) ◽  
pp. 41
Author(s):  
Christian Carpéné ◽  
Francisco Les ◽  
Josep Mercader ◽  
Saioa Gomez-Zorita ◽  
Jean-Louis Grolleau ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Glucose Transport ◽  
Amine Oxidase ◽  
Direct Action ◽  
Antidepressant Drugs ◽  
Drug Repurposing ◽  
Human Adipocytes ◽  
Fat Cell

Treatment with several antipsychotic drugs exhibits a tendency to induce weight gain and diabetic complications. The proposed mechanisms by which the atypical antipsychotic drug olanzapine increases body weight include central dysregulations leading to hyperphagia and direct peripheral impairment of fat cell lipolysis. Several investigations have reproduced in vitro direct actions of antipsychotics on rodent adipocytes, cultured preadipocytes, or human adipose tissue-derived stem cells. However, to our knowledge, no such direct action has been described in human mature adipocytes. The aim of the present study was to compare in human adipocytes the putative direct alterations of lipolysis by antipsychotics (haloperidol, olanzapine, ziprazidone, risperidone), antidepressants (pargyline, phenelzine), or anxiolytics (opipramol). Lipolytic responses to the tested drugs, and to recognized lipolytic (e.g., isoprenaline) or antilipolytic agents (e.g., insulin) were determined, together with glucose transport and amine oxidase activities in abdominal subcutaneous adipocytes from individuals undergoing plastic surgery. None of the tested drugs were lipolytic. Surprisingly, only opipramol exhibited substantial antilipolytic properties in the micromolar to millimolar range. An opipramol antilipolytic effect was evident against isoprenaline-, forskolin-, or atrial natriuretic peptide-stimulated lipolysis. Opipramol did not impair insulin activation of glucose transport but inhibited monoamine oxidase (MAO) activity to the same extent as antidepressants recognized as MAO inhibitors (pargyline, harmine, or phenelzine), whereas antipsychotics were inefficient. Considering its unique properties, opipramol, which is not associated with weight gain in treated patients, is a good candidate for drug repurposing because it limits exaggerated lipolysis, prevents hydrogen peroxide release by amine oxidases in adipocytes, and is thereby of potential use to limit lipotoxicity and oxidative stress, two deleterious complications of diabetes and obesity.

Amine oxidase substrates mimic several of the insulin effects on adipocyte differentiation in 3T3 F442A cells

2001 ◽  
Vol 356 (3) ◽  
pp. 769-777 ◽  
Author(s):  
Emi FONTANA ◽  
Jérémie BOUCHER ◽  
Luc MARTI ◽  
José Miguel LIZCANO ◽  
Xavier TESTAR ◽  
...  
Keyword(s):  
Glucose Transport ◽  
Glucose Transporter ◽  
Adipocyte Differentiation ◽  
Amine Oxidase ◽  
Chronic Administration ◽  
Mao Inhibitor ◽  
Amine Oxidation ◽  
Adipose Conversion ◽  
Triacylglycerol Accumulation ◽  
Stimulation Of

We have previously reported that substrates of monoamine oxidase (MAO) and semicarbazide-sensitive amine oxidase (SSAO) exert short-term insulin-like effects in rat adipocytes, such as stimulation of glucose transport. In the present work, we studied whether these substrates could also mimic long-term actions of insulin. Adipose differentiation of 3T3 F442A cells, which is highly insulin-dependent, served as a model to test the effects of sustained administration of amine oxidase substrates. Daily treatment of confluent cells with 0.75mM tyramine (a substrate of MAO and SSAO) or benzylamine (a substrate of SSAO) over 1 week caused the acquisition of typical adipocyte morphology. The stimulation of protein synthesis and triacylglycerol accumulation caused by tyramine or benzylamine reached one half of that promoted by insulin. This effect was insensitive to pargyline (an MAO inhibitor), but was inhibited by semicarbazide (an SSAO inhibitor) and by N-acetylcysteine (an antioxidant agent), suggesting the involvement of the H2O2 generated during SSAO-dependent amine oxidation. Chronic administration of amine oxidase substrates also induced the emergence of adipose conversion markers, such as aP2, glycerol-3-phosphate dehydrogenase, the glucose transporter GLUT4, and SSAO itself. Moreover, cells treated with amines acquired the same insulin sensitivity regarding glucose transport as adipocytes classically differentiated with insulin. In all, most of the adipogenic effects of amines were additive to insulin. Our data reveal that amine oxidase substrates partially mimic the adipogenic effect of insulin in cultured preadipocytes. Furthermore, they suggest that SSAO not only represents a novel late marker of adipogenesis, but could also be directly involved in the triggering of terminal adipocyte differentiation.

scholarly journals Dietary Phenolic Compounds Interfere with the Fate of Hydrogen Peroxide in Human Adipose Tissue but Do Not Directly Inhibit Primary Amine Oxidase Activity

2016 ◽  
Vol 2016 ◽  
pp. 1-15 ◽  
Author(s):  
Christian Carpéné ◽  
Mounia Hasnaoui ◽  
Balázs Balogh ◽  
Peter Matyus ◽  
Alfredo Fernández-Quintela ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Phenolic Compounds ◽  
Primary Amine ◽  
Amine Oxidase ◽  
Human Adipose Tissue ◽  
3D Models ◽  
Fluorescent Detection ◽  
Computational Docking ◽  
Amine Oxidation ◽  
Primary Amine Oxidase

Resveratrol has been reported to inhibit monoamine oxidases (MAO). Many substrates or inhibitors of neuronal MAO interact also with other amine oxidases (AO) in peripheral organs, such as semicarbazide-sensitive AO (SSAO), known as primary amine oxidase, absent in neurones, but abundant in adipocytes. We asked whether phenolic compounds (resveratrol, pterostilbene, quercetin, and caffeic acid) behave as MAO and SSAO inhibitors. AO activity was determined in human adipose tissue. Computational docking and glucose uptake assays were performed in 3D models of human AO proteins and in adipocytes, respectively. Phenolic compounds fully inhibited the fluorescent detection of H2O2generated during MAO and SSAO activation by tyramine and benzylamine. They also quenched H2O2-induced fluorescence in absence of biological material and were unable to abolish the oxidation of radiolabelled tyramine and benzylamine. Thus, phenolic compounds hampered H2O2detection but did not block AO activity. Only resveratrol and quercetin partially impaired MAO-dependent [14C]-tyramine oxidation and behaved as MAO inhibitors. Phenolic compounds counteracted the H2O2-dependent benzylamine-stimulated glucose transport. This indicates that various phenolic compounds block downstream effects of H2O2produced by biogenic or exogenous amine oxidation without directly inhibiting AO. Phenolic compounds remain of interest regarding their capacity to limit oxidative stress rather than inhibiting AO.

β-adrenoceptor antagonists and nightmares: A pharmacoepidemiological–pharmacodynamic study

2021 ◽  
pp. 026988112110348
Author(s):  
Philippe Garcia ◽  
Jean-Louis Montastruc ◽  
Vanessa Rousseau ◽  
Jacques Hamard ◽  
Agnès Sommet ◽  
...  
Keyword(s):  
Individual Case ◽  
World Health ◽  
Lipid Solubility ◽  
Multivariate Logistic Regression ◽  
Individual Case Safety Report ◽  
High Lipid ◽  
Increased Risk ◽  
Pharmacodynamic Analysis ◽  
Health Organization ◽  
High Lipid Solubility

Aim: To compare different β-adrenoceptor antagonists for the risk of reporting nightmare. Methods: The study involved two approaches: first, we investigated in VigiBase®, the World Health Organization Individual Case Safety Report (ICSR) database, the disproportionality between exposure to each β-adrenoceptor antagonists and reports of nightmares between 1967 and 2019. Second, in a pharmacoepidemiological–pharmacodynamic analysis, we assessed whether use of β-adrenoceptor antagonists with moderate and high lipid solubility or strong 5-HT1A affinity were associated with an increased risk of reporting nightmares. We conducted multivariate logistic regression to estimate reporting odds ratios (RORs) of nightmares compared to all other adverse drug reactions. Results: Of the 126,964 reports recorded with β-adrenoceptor antagonists, 1138 (0.9%) were nightmares. The highest risk of reporting a nightmare was found with exposure of pindolol (adjusted ROR 2.82, 95%CI, 2.19–3.61), metoprolol (1.89, 1.66–2.16), and alprenolol (1.77, 1.06–2.97). Compared to use of low lipid solubility β-adrenoceptor antagonists, use of moderate or high lipid solubility β-adrenoceptor antagonists were significantly more associated with nightmare reports (aROR moderate vs. low 1.72, 95%CI 1.47–2.00 and aROR high vs. low 1.84, 95%CI 1.53–2.22). Use of moderate or high 5-HT1A affinity of β-adrenoceptor antagonists was associated with an increased ROR of nightmares compared with low 5-HT1A affinity of β-adrenoceptor antagonists (aROR moderate vs. low 1.22, 95%CI 1.04–1.43 and aROR high vs. low 2.46, 95%CI 1.93–3.13). Conclusion: In our large pharmacovigilance study, nightmares are more frequently reported for pindolol and metoprolol, and among β-adrenoceptor antagonists with high lipid solubility and high 5-HT1A receptor affinity.

Inflammation as a target of minocycline: special interest in the regulation of inflammasome signaling

Inflammasome ◽  
2014 ◽  
Vol 1 (1) ◽  
Author(s):  
Anu Kauppinen ◽  
Antero Salminen ◽  
Kai Kaarniranta
Keyword(s):  
Side Effects ◽  
Special Interest ◽  
Protein Complexes ◽  
Wide Spectrum ◽  
Lipid Solubility ◽  
Intracellular Protein ◽  
Tissue Penetration ◽  
High Lipid ◽  
High Lipid Solubility ◽  
Better Than

AbstractMinocycline is a wide-spectrum antibiotic derived from tetracycline. In addition to its anti-microbial activity, minocycline is known to possess several immunomodulatory and neuroprotective properties. Fewer severe side effects and more efficient tissue penetration make minocycline better than its parent tetracycline. Doxycycline competes with minocycline in improved biological half-life but minocycline becomes more rapidly absorbed in tissues than doxycycline. Due to its high lipid solubility, minocycline also crosses the blood-brain barrier easily, which increases its relevance in the treatment of diseases beyond the barriers. Inflammasomes are intracellular protein complexes which become primed via NF-kB and MAPK pathways, and activated by various PAMPs and DAMPs. In this article, we hypothese about the capability of minocycline to regulate inflammasomes as part of its anti-inflammatory activity. The hypothesis is based on the ability of minocycline to regulate signals essential to both the priming and the activation of inflammasome signaling

The Hydrolysis of Ammonium Ions in Sea Water-a Theoretical Study

1974 ◽  
Vol 54 (3) ◽  
pp. 565-580 ◽  
Author(s):  
M. Whitfield
Keyword(s):  
Sea Water ◽  
Practical Importance ◽  
Lipid Solubility ◽  
Ammonium Ions ◽  
Theoretical Approaches ◽  
High Lipid ◽  
Ionic Equilibria ◽  
Good Account ◽  
High Lipid Solubility ◽  
Hydrolysis Of

A number of procedures are now available for calculating the effects of ionic inter-actions on the behaviour of solutions as complex as sea water (Whitfield, 1973 a). These procedures are able to give a good account of the properties of the major electrolyte components (Leyendekkers, 1973 a; Robinson & Wood, 1972; Whitfield, 19736) and of the colligative properties of sea water (Robinson & Wood, 1972; Whitfield, 1973 c, d). However, greatest interest centres around the possibility of predicting the effects of these major components on the multitude of ionic equilibria that influence the properties of the less abundant constituents that are of greater biological and geological importance. It is here that the newer approaches to marine chemistry are weakest because suitable thermodynamic data are lacking. One system of practical importance that can be studied using a variety of theoretical approaches is the acid ionization of ammonium ions represented by the equation The toxicity of ammonium salts to freshwater life has been shown to be strongly dependent on the pH in a manner that is consistent with un-ionized ammonia (NH3) being the most lethal fraction (see, for example, Wuhrmann & Woker, 1948; Downing & Merkens, 1955; Lloyd & Herbert, i960; Hemens, 1966; and Brown, 1968). These papers and many others have been thoroughly reviewed (EIFAC Technical Paper no. 11, 1970, Kemp, Abrams & Overbeck, 1971). The free base (NH3) has a relatively high lipid solubility because it carries no charge and is therefore able to diffuse quite readily across cell membranes (Fromm & Gillette, 1968).

Sign in / Sign up

Export Citation Format

Share Document