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.

Optical oxygen sensors based on Pt(II) porphyrin dye immobilized on S-layer protein matrices.

This paper describes the development of planar and fiber optic oxygen sensors utilizing surface layer (S-layer) proteins as immobilization matrix for oxygen sensitive dyes. S-layer proteins have the intrinsic capability to reassemble into two-dimensional arrays in suspension and at interfaces. Due to their crystalline character the distribution of functional groups, such as carboxylic groups, is repeated with the periodicity of the lattice and thus allows the reproducible and geometrically distinct binding of functional molecules. For the development of oxygen sensors an oxygen sensitive Pt(II) porphyrin dye was covalently bound to the S-layer matrix. Measurement of the oxygen concentration was performed by phase modulation fluorimetry. Setups comprising low cost optoelectronic components like LEDs and silicon photodiodes were constructed. For both sensor setups (planar and fiber optic) variations in the oxygen concentrations resulted in distinct and reproducible changes in luminescence lifetime and intensity. The luminescence quenching efficiency of these sensors was found to be 1.5-1.9 (expressed as the ratio of signal under nitrogen and air) which compares well to other sensor systems using luminophores embedded in polymer matrices. These results demonstrated the application potential of S-layers as immobilization matrices in the development of (bio-)sensors.

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.