Differences in Upper and Lower Body Adipose Tissue Oxygen Tension Contribute to the Adipose Tissue Phenotype in Humans.

Context and Objectives: Upper and lower body adipose tissue (AT) exhibits opposing associations with obesity-related cardiometabolic diseases. Recent studies have suggested that altered AT oxygen tension (pO2) may contribute to AT dysfunction. Here, we compared in vivo abdominal (ABD) and femoral (FEM) subcutaneous AT pO2 in women who are overweight and have obesity, and investigated the effects of physiological AT pO2 on human adipocyte function. Design: ABD and FEM subcutaneous AT pO2 and AT blood flow (ATBF) were assessed in eight [BMI (body mass index) 34.4 ± 1.6 kg/m2] postmenopausal women who were overweight with obesity and impaired glucose metabolism. ABD and FEM AT biopsy specimens were collected to determine adipocyte morphology and AT gene expression. Moreover, the effects of prolonged exposure (14 days) to physiological AT pO2 on adipokine expression/secretion, mitochondrial respiration, and glucose uptake were investigated in differentiated human multipotent adipose-derived stem cells. Results: AT pO2 was higher in ABD than FEM AT (62.7 ± 6.6 vs 50.0 ± 4.5 mm Hg, P = 0.013), whereas ATBF was comparable between depots. Maximal uncoupled oxygen consumption rates were substantially lower in ABD than FEM adipocytes for all pO2 conditions. Low physiological pO2 (5% O2) decreased proinflammatory gene expression, increased basal glucose uptake, and altered adipokine secretion in ABD and FEM adipocytes. Conclusions: We demonstrated for the first time, to our knowledge, that AT pO2 is higher in ABD than FEM subcutaneous AT in women who are overweight/with obesity, partly due to a lower oxygen consumption rate in ABD adipocytes. Moreover, low physiological pO2 decreased proinflammatory gene expression and improved the metabolic phenotype in differentiated human adipocytes, whereas more heterogeneous effects on adipokine secretion were found.

Synthesis and characterization of naphthalimide-functionalized polynorbornenes.

ABSTRACT: Highly fluorescent and photostable (2-alkyl)-1H-benzo[de]isoquinoline-1,3(2H)-diones with a polymerizable norbornene scaffold have been synthesized and polymerized using ring-opening metathesis polymerization. The monomers presented herein could be polymerized in a living fashion, using different comonomers and different monomer ratios. All obtained materials showed good film-forming properties and bright fluorescence caused by the incorporated push-pull chromophores. Additionally, one of the monomers containing a methylpiperazine functionality showed protonation-dependent photoinduced electron transfer which opens up interesting applications for logic gates and sensing.

A luminescence lifetime-based capillary oxygen sensor utilizing monolithically integrated organic photodiodes.

A novel optical sensor device monolithically integrated on a glass capillary is presented. Therefore, we took advantage of the ability to fabricate organic optoelectronic devices on non-planar substrates. The functionality of the concept is demonstrated by realizing an integrated oxygen sensor based on luminescence decay time measurement.

Increased adipose tissue oxygen tension in obese compared with lean men is accompanied by insulin resistance, impaired adipose tissue capillarization, and inflammation.

BACKGROUND: Adipose tissue (AT) dysfunction in obesity contributes to chronic, low-grade inflammation that predisposes to type 2 diabetes mellitus and cardiovascular disease. Recent in vitro studies suggest that AT hypoxia may induce inflammation. We hypothesized that adipose tissue blood flow (ATBF) regulates AT oxygen partial pressure (AT P(O2)), thereby affecting AT inflammation and insulin sensitivity. METHODS AND RESULTS: We developed an optochemical measurement system for continuous monitoring of AT P(O2) using microdialysis. The effect of alterations in ATBF on AT P(O2) was investigated in lean and obese subjects with both pharmacological and physiological approaches to manipulate ATBF. Local administration of angiotensin II (vasoconstrictor) in abdominal subcutaneous AT decreased ATBF and AT P(O2), whereas infusion of isoprenaline (vasodilator) evoked opposite effects. Ingestion of a glucose drink increased ATBF and AT P(O2) in lean subjects, but these responses were blunted in obese individuals. However, AT P(O2) was higher (hyperoxia) in obese subjects despite lower ATBF, which appears to be explained by lower AT oxygen consumption. This was accompanied by insulin resistance, lower AT capillarization, lower AT expression of genes encoding proteins involved in mitochondrial biogenesis and function, and higher AT gene expression of macrophage infiltration and inflammatory markers. CONCLUSIONS: Our findings establish ATBF as an important regulator of AT P(O2). Nevertheless, obese individuals exhibit AT hyperoxia despite lower ATBF, which seems to be explained by lower AT oxygen consumption. This is accompanied by insulin resistance, impaired AT capillarization, and higher AT gene expression of inflammatory cell markers. CLINICAL TRIAL REGISTRATION- URL: http://www.trialregister.nl. Unique identifier: NTR2451.

Continuous oxygen monitoring in subcutaneous adipose tissue using microdialysis.

A measurement system, consisting of an optochemical glass capillary oxygen sensor, an optoelectronic measuring unit and a microdialysis catheter (CMA 60) for the extraction of the biological fluid from the subcutaneous adipose tissue of critically ill patients is reported. The capillary sensor is based on the oxygen sensitive dye platinum (II) meso-tetra(pentafluorophenyl) porphyrin (Pt-TFPP) incorporated in a polystyrene matrix. The measuring system has been tested in vitro and in vivo. In particular in vitro long-term stability of the sensor has been investigated in different measurement media (elomel, 5% mannitol, Ringer, dialysed blood). The influence of different flow rates from 0.1 up to 7.0 microl min(-1) on the sensor response as well as the oxygen recovery rate are discussed. The presented measurement system allows the measurement of oxygen in biological fluid in the range from 0 to 300 mmHg, with a resolution better than 1 mmHg and high accuracy (better than +/-1 mmHg absolute). Finally, the suitability of the described measurement system for the continuous oxygen monitoring in subcutaneous adipose tissue has been proved in in vivo investigations performed on test animals.

Luminescence lifetime-based carbon dioxide optical sensor for clinical applications.

The development of both an optical planar and capillary based carbon dioxide sensor, which final aim is pCO2 monitoring in adipose tissue of critically ill patients, is reported. The sensor is based on the measuring principle of phase fluorometry using a dual luminophore referencing scheme (DLR) to convert the CO2 dependent intensity signal into phase domain. The CO2 sensors have been prepared by incorporating two appropriate luminophores and a phase transfer agent in a same hydrophobic polymer as matrix. The short-lifetime luminophore used as pH indicator is 8-hydroxypyrene-1,3,6-trisulfonic acid trisodium salt (HPTS). The second inert luminophore is the long-lifetime dye Ruthenium(II) tris(4,7-diphenyl-1,10-phenanthroline) (Ru(dpp)3(2+)), which has been made insensitive to oxygen by immobilising in a suitable oxygen impermeable polymer. As phase transfer agent, tetraoctylammonium hydroxide (TOA-OH) has been chosen. Both sensor types have been characterised with respect to optimise sensitivity and mechanical stability. For this purpose, several polymers, such as ethylcellulose, eudragit RL100 (EG), copolymer eudragit/poly(ethylene glycol) (PEG) and silicone have been examined as appropriate matrix for incorporation of two indicators. The largest phase shift up to 13 degrees and 15 degrees has been observed in the case of silicone and copolymer EG/PEG, respectively, and they have been in detail examined in terms of sensitivity and stability. The presented sensors enable the measurement of pCO2 in the range from 0 to 150 mmHg, with a resolution of 0.5 mmHg and an accuracy of +/-1 mmHg absolute or less than 7% of the read-out value. All measurements have been carried out only in aqueous solutions before clinical measurements.