Prediction of Naphthalene Bioaccumulation Using an Adipocyte Cell Line Model

Viravaidya, Kwanchanok; Shuler, Michael L.

doi:10.1021/bp0101684

Cited by 11 publications

(11 citation statements)

References 37 publications

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“…Briefly, epididymal fat pads were dissected, minced, and digested using collagenase type I (Sigma, St. Louis, MO) in Krebs-Ringer HEPES buffer supplemented with 20 mg/ml BSA at 37°C for 2 h. Preadipocytes were isolated and cultured in Dulbecco's modified Eagle's medium containing 15 mmol/l NaHCO 3 , 15 mmol/l HEPES, 33 mol/l biotin, 17 mol/l pantothenate, 0.5 mol/l human insulin, and 0.2 nmol/l triiodothyronine. Differentiation of preadipocytes to adipocytes was induced by addition of a hormonal cocktail (1 g/ml insulin, 0.25 mol/l dexamethasone, and 0.5 mmol/l isobutylmethylxanthine) and confirmed morphologically by multiple oil red Ostained fat droplets in the cytoplasm (45). Analysis of adipocyte size.…”

Section: Methodsmentioning

confidence: 99%

Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1

et al. 2004

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Increased plasminogen activator inhibitor 1 (PAI-1) has been linked to not only thrombosis and fibrosis but also to obesity and insulin resistance. Increased PAI-1 levels have been presumed to be consequent to obesity. We investigated the interrelationships of PAI-1, obesity, and insulin resistance in a high-fat/high-carbohydrate (HF) diet-induced obesity model in wild-type (WT) and PAI-1-deficient mice (PAI-1 ؊/؊ ). Obesity and insulin resistance developing in WT mice on an HF diet were completely prevented in mice lacking PAI-1. PAI-1 ؊/؊ mice on an HF diet had increased resting metabolic rates and total energy expenditure compared with WT mice, along with a marked increase in uncoupling protein 3 mRNA expression in skeletal muscle, likely mechanisms contributing to the prevention of obesity. In addition, insulin sensitivity was enhanced significantly in PAI-1 ؊/؊ mice on an HF diet, as shown by euglycemichyperinsulinemic clamp studies. Peroxisome proliferator-activated receptor (PPAR)-␥ and adiponectin mRNA, key control molecules in lipid metabolism and insulin sensitivity, were maintained in response to an HF diet in white adipose tissue in PAI-1 ؊/؊ mice, contrasting with downregulation in WT mice. This maintenance of PPAR-␥ and adiponectin may also contribute to the observed maintenance of body weight and insulin sensitivity in PAI-1 ؊/؊ mice. Treatment in WT mice on an HF diet with the angiotensin type 1 receptor antagonist to downregulate PAI-1 indeed inhibited PAI-1 increases and ameliorated diet-induced obesity, hyperglycemia, and hyperinsulinemia. PAI-1 deficiency also enhanced basal and insulin-stimulated glucose uptake in adipose cells in vitro. Our data suggest that PAI-1 may not merely increase in response to obesity and insulin resistance, but may have a direct causal role in obesity and insulin resistance. Inhibition of PAI-1 might provide a novel anti-obesity and anti-insulin resistance treatment. Diabetes 53: 336 -346, 2004

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Section: Methodsmentioning

confidence: 99%

Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1

et al. 2004

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“…These results indicate that the lipid-gel system is superior to the PDMS system in mimicking the volumetric accumulation of naphthalene in adipocytes. Because an earlier study (Viravaidya and Shuler, 2002) showed a good correlation between accumulation kinetics in the differentiated 3T3-L1 adipocytes and primary adipocytes, we infer that the lipid-gel system is a good model for primary adipocyte tissue.…”

Section: Naphthalene Accumulation Studymentioning

confidence: 56%

“…3T3-L1 adipocytes were subjected to the differentiation process 20 days before the accumulation study was initiated. Cells were monitored using a phase-contrast microscope with a Â100 objectives (Viravaidya and Shuler, 2002).…”

Section: Cell Culture and Adipocyte Differentiationmentioning

confidence: 99%

“…Transformed rodent preadipocyte-like cell lines, commonly called preadipocyte cell lines, have been introduced as an alternative to study the bioaccumulation of various chemicals in adipose tissue. Rodent preadipocyte cells can differentiate into adipocytes (fat cells) when exposed to the appropriate stimuli (Cornelius et al, 1994;Gregoire et al, 1998) Among several rodent preadipocyte cell lines tested, the 3T3-L1 adipocyte cell line accumulated the highest level of intracellular lipid and was shown to mimic the kinetics and extent of absorption of naphthalene in primary adipocytes relatively well (Viravaidya and Shuler, 2002). Although promising, there are several concerns in utilizing the cell-line model.…”

Section: Introductionmentioning

confidence: 99%

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Lipid‐gel and poly(dimethylsiloxane) film to mimic bioaccumulation in adipocytes

Viravaidya¹,

Jan²,

Shuler³

2004

Biotech & Bioengineering

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Bioaccumulation is an increasingly important consideration in validation studies of the safety and efficacy of potential drugs. Although an "adipocyte" cell line model has been proven successful to mimic the accumulation of naphthalene in adipocytes, the prolonged incubation time limits its use in high-throughput studies and reduces reproducibility. In this investigation, naphthalene and naphthol accumulation and uptake kinetics of thin poly(dimethylsiloxane) (PDMS) film and lipid nanospheres suspended in a crosslinked gelatin gel (lipid-gel) were compared with those of adipocytes. Unlike the PDMS film, the lipid-gel can mimic the kinetics and extent of naphthalene accumulation in the adipocytes reasonably well. However, the lipid-gel accumulated about twice as much naphthol as the adipocytes, suggesting that hydrophobicity/hydrophilicity of the metabolite may be an important factor in the accuracy of accumulation studies with the lipid-gel. Nonetheless, the lipid-gel system shows promise as an inexpensive, convenient, and reproducible fat mimic for bioaccumulation studies.

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“…The differentiated cell lines accumulate 200 times more naphthalene than the undifferentiated form of these cell lines. The kinetics and extent of naphthalene uptake per gram of lipid in the differentiated preadipocyte cell lines is a good mimic of that observed with primary adipocytes (85). Thus a fourcompartment system can be constructed, and preliminary studies reveal that all four cell types can be seeded in such a device and operated for 24 h with a recirculating medium while retaining cellular viability in all compartments (Viravaidya, unpublished results).…”

Section: Microscopic Cell Culture Analogmentioning

confidence: 87%

Integration of Cell Culture and Microfabrication Technology

Park

Shuler

2003

Biotechnology Progress

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479

337

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Recent progress in cell culture and microfabrication technologies has contributed to the development of cell-based biosensors for the functional characterization and detection of drugs, pathogens, toxicants, and odorants. The cell-based biosensors are composed of two transducers, where the primary transducer is cellular and the secondary transducer is typically electrical. Advances in gene manipulation and cell culture techniques have contributed to the development of the cell as a transducer, while microfabrication techniques have been applied to the development of integrating the cell with the second transducer. Cellular patterning using microfabrication techniques is essential for cell-based biosensors, cell culture analogues, tissue engineering, and fundamental studies of cell biology. The photolithographic technique is highly developed and has been widely used for patterning cells. Recently, a set of alternative techniques, largely based on soft lithoghraphy, has been developed for biological applications. Those techniques include microcontact printing, microfluidic patterning using microchannels, and laminar flow patterning. A classical metallic stencil patterning method has been improved by employing a rubber-like stencil. These cellular micropatterning techniques have been usefully employed to understand questions in fundamental cell biology, especially cellular interactions with various materials and other cells. Using these micropatterning tecchniques and insights into the interaction of cellular biology with surfaces, a wide array of biosensors have been developed. In this manuscript examples of cell-based biosensors are described. Neurons have a great potential for use in a cell-based biosensor because they are electrically excitable cells, from which electrical signals are generated with the binding of detecting molecules. Consequently, the electrical signals generated in the cell can be determined in a noninvasive manner. A microphysiometer is a device to detect functional responses from cells by measuring the change of extracellular pH. The main application of the microphysiometer is the analysis of functional responses of cells upon receptor stimulation. Development of a microscale cell culture analogue system, an in vitro animal or human surrogate, is another promising area using cell culture and microfabrication technologies. Such devices are potentially very useful in the fields of toxicology and drug testing because they may increase the accuracy of in vitro predictions, simplify testing procedures, and reduce the cost of such tests, allowing many more tests to be done with a limited set of resources.

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Prediction of Naphthalene Bioaccumulation Using an Adipocyte Cell Line Model

Cited by 11 publications

References 37 publications

Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1

Prevention of Obesity and Insulin Resistance in Mice Lacking Plasminogen Activator Inhibitor 1

Lipid‐gel and poly(dimethylsiloxane) film to mimic bioaccumulation in adipocytes

Integration of Cell Culture and Microfabrication Technology

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