Matching Items (66)
128752-Thumbnail Image.png
Description

Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect

Type 2 diabetes (T2D) is a complex metabolic disease that is more prevalent in ethnic groups such as Mexican Americans, and is strongly associated with the risk factors obesity and insulin resistance. The goal of this study was to perform whole genome gene expression profiling in adipose tissue to detect common patterns of gene regulation associated with obesity and insulin resistance. We used phenotypic and genotypic data from 308 Mexican American participants from the Veterans Administration Genetic Epidemiology Study (VAGES). Basal fasting RNA was extracted from adipose tissue biopsies from a subset of 75 unrelated individuals, and gene expression data generated on the Illumina BeadArray platform. The number of gene probes with significant expression above baseline was approximately 31,000. We performed multiple regression analysis of all probes with 15 metabolic traits. Adipose tissue had 3,012 genes significantly associated with the traits of interest (false discovery rate, FDR ≤ 0.05). The significance of gene expression changes was used to select 52 genes with significant (FDR ≤ 10-4) gene expression changes across multiple traits. Gene sets/Pathways analysis identified one gene, alcohol dehydrogenase 1B (ADH1B) that was significantly enriched (P < 10-60) as a prime candidate for involvement in multiple relevant metabolic pathways. Illumina BeadChip derived ADH1B expression data was consistent with quantitative real time PCR data. We observed significant inverse correlations with waist circumference (2.8 x 10[superscript -9]), BMI (5.4 x 10-6), and fasting plasma insulin (P < 0.001). These findings are consistent with a central role for ADH1B in obesity and insulin resistance and provide evidence for a novel genetic regulatory mechanism for human metabolic diseases related to these traits.

ContributorsWinnier, Deidre A. (Author) / Fourcaudot, Marcel (Author) / Norton, Luke (Author) / Abdul-Ghani, Muhammad A. (Author) / Hu, Shirley L. (Author) / Farook, Vidya S. (Author) / Coletta, Dawn (Author) / Kumar, Satish (Author) / Puppala, Sobha (Author) / Chittoor, Geetha (Author) / Dyer, Thomas D. (Author) / Arya, Rector (Author) / Carless, Melanie (Author) / Lehman, Donna M. (Author) / Curran, Joanne E. (Author) / Cromack, Douglas T. (Author) / Tripathy, Devjit (Author) / Blangero, John (Author) / Duggirala, Ravindranath (Author) / Goring, Harald H. H. (Author) / DeFronzo, Ralph A. (Author) / Jenkinson, Christopher P. (Author) / College of Liberal Arts and Sciences (Contributor)
Created2015-04-01
156088-Thumbnail Image.png
Description
Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular

Obesity impairs skeletal muscle maintenance and regeneration, a condition that can progressively lead to muscle loss, but the mechanisms behind it are unknown. Muscle is primarily composed of multinucleated cells called myotubes which are derived by the fusion of mononucleated myocytes. A key mediator in this process is the cellular fusion protein syncytin-1. This led to the hypothesis that syncytin-1 could be decreased in the muscle of obese/insulin resistant individuals. In contrast, it was found that obese/insulin resistant subjects had higher syncytin-1 expression in the muscle compared to that of the lean subjects. Across the subjects, syncytin-1 correlated significantly with body mass index, percent body fat, blood glucose and HbA1c levels, insulin sensitivity and muscle protein fractional synthesis rate. The concentrations of specific plasma fatty acids, such as the saturated fatty acid (palmitate) and monounsaturated fatty acid (oleate) are known to be altered in obese/insulin resistant humans, and also to influence the protein synthesis in muscle. Therefore, it was evaluated that the effects of palmitate and oleate on syncytin-1 expression, as well as 4E-BP1 phosphorylation, a key mechanism regulating muscle protein synthesis in insulin stimulated C2C12 myotubes. The results showed that treatment with 20 nM insulin, 300 µM oleate, 300 µM oleate +20 nM insulin and 300 µM palmitate + 300 µM oleate elevated 4E-BP1 phosphorylation. At the same time, 20 nM insulin, 300 µM palmitate, 300 µM oleate + 20 nM insulin and 300 µM palmitate + 300 µM oleate elevated syncytin-1 expression. Insulin stimulated muscle syncytin-1 expression and 4E-BP1 phosphorylation, and this effect was comparable to that observed in the presence of oleate alone. However, the presence of palmitate + oleate diminished the stimulatory effect of insulin on muscle syncytin-1 expression and 4E-BP1 phosphorylation. These findings indicate oleate but not palmitate increased total 4E-BP1 phosphorylation regardless of insulin and the presence of palmitate in insulin mediated C2C12 cells. The presence of palmitate inhibited the upregulation of total 4EB-P1 phosphorylation. Palmitate but not oleate increased syncytin-1 expression in insulin mediated C2C12 myotubes. It is possible that chronic hyperinsulinemia in obesity and/or elevated levels of fatty acids such as palmitate in plasma could have contributed to syncytin-1 overexpression and decreased muscle protein fractional synthesis rate in obese/insulin resistant human muscle.
ContributorsRavichandran, Jayachandran (Author) / Katsanos, Christos (Thesis advisor) / Coletta, Dawn (Committee member) / Dickinson, Jared (Committee member) / Arizona State University (Publisher)
Created2017
128791-Thumbnail Image.png
Description

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely

Our previous studies show reduced abundance of the β-subunit of mitochondrial H+-ATP synthase (β-F1-ATPase) in skeletal muscle of obese individuals. The β-F1-ATPase forms the catalytic core of the ATP synthase, and it is critical for ATP production in muscle. The mechanism(s) impairing β-F1-ATPase metabolism in obesity, however, are not completely understood. First, we studied total muscle protein synthesis and the translation efficiency of β-F1-ATPase in obese (BMI, 36±1 kg/m2) and lean (BMI, 22±1 kg/m2) subjects. Both total protein synthesis (0.044±0.006 vs 0.066±0.006%·h-1) and translation efficiency of β-F1-ATPase (0.0031±0.0007 vs 0.0073±0.0004) were lower in muscle from the obese subjects when compared to the lean controls (P<0.05). We then evaluated these same responses in a primary cell culture model, and tested the specific hypothesis that circulating non-esterified fatty acids (NEFA) in obesity play a role in the responses observed in humans. The findings on total protein synthesis and translation efficiency of β-F1-ATPase in primary myotubes cultured from a lean subject, and after exposure to NEFA extracted from serum of an obese subject, were similar to those obtained in humans. Among candidate microRNAs (i.e., non-coding RNAs regulating gene expression), we identified miR-127-5p in preventing the production of β-F1-ATPase. Muscle expression of miR-127-5p negatively correlated with β-F1-ATPase protein translation efficiency in humans (r = – 0.6744; P<0.01), and could be modeled in vitro by prolonged exposure of primary myotubes derived from the lean subject to NEFA extracted from the obese subject. On the other hand, locked nucleic acid inhibitor synthesized to target miR-127-5p significantly increased β-F1-ATPase translation efficiency in myotubes (0.6±0.1 vs 1.3±0.3, in control vs exposure to 50 nM inhibitor; P<0.05). Our experiments implicate circulating NEFA in obesity in suppressing muscle protein metabolism, and establish impaired β-F1-ATPase translation as an important consequence of obesity.

ContributorsTran, Lee (Author) / Hanavan, Paul (Author) / Campbell, Latoya (Author) / De Filippis, Elena (Author) / Lake, Douglas (Author) / Coletta, Dawn (Author) / Roust, Lori R. (Author) / Mandarino, Lawrence (Author) / Carroll, Chad C. (Author) / Katsanos, Christos (Author) / College of Health Solutions (Contributor)
Created2016-08-17
128798-Thumbnail Image.png
Description

Exposure to fine particles can cause various diseases, and an easily accessible method to monitor the particles can help raise public awareness and reduce harmful exposures. Here we report a method to estimate PM air pollution based on analysis of a large number of outdoor images available for Beijing, Shanghai

Exposure to fine particles can cause various diseases, and an easily accessible method to monitor the particles can help raise public awareness and reduce harmful exposures. Here we report a method to estimate PM air pollution based on analysis of a large number of outdoor images available for Beijing, Shanghai (China) and Phoenix (US). Six image features were extracted from the images, which were used, together with other relevant data, such as the position of the sun, date, time, geographic information and weather conditions, to predict PM2.5 index. The results demonstrate that the image analysis method provides good prediction of PM2.5 indexes, and different features have different significance levels in the prediction.

ContributorsLiu, Chenbin (Author) / Tsow, Francis (Author) / Zou, Yi (Author) / Tao, Nongjian (Author) / Biodesign Institute (Contributor)
Created2016-02-01
128669-Thumbnail Image.png
Description

The production, characterization, and antioxidant capacity of the carotenoid fucoxanthin from the marine diatom Odontella aurita were investigated. The results showed that low light and nitrogen-replete culture medium enhanced the biosynthesis of fucoxanthin. The maximum biomass concentration of 6.36 g L-1 and maximum fucoxanthin concentration of 18.47 mg g-1 were

The production, characterization, and antioxidant capacity of the carotenoid fucoxanthin from the marine diatom Odontella aurita were investigated. The results showed that low light and nitrogen-replete culture medium enhanced the biosynthesis of fucoxanthin. The maximum biomass concentration of 6.36 g L-1 and maximum fucoxanthin concentration of 18.47 mg g-1 were obtained in cultures grown in a bubble column photobioreactor (Ø 3.0 cm inner diameter), resulting in a fucoxanthin volumetric productivity of 7.96 mg L-1 day-1. A slight reduction in biomass production was observed in the scaling up of O. aurita culture in a flat plate photobioreactor, yet yielded a comparable fucoxanthin volumetric productivity. A rapid method was developed for extraction and purification of fucoxanthin. The purified fucoxanthin was identified as all-trans-fucoxanthin, which exhibited strong antioxidant properties, with the effective concentration for 50% scavenging (EC50) of 1,1-dihpenyl-2-picrylhydrazyl (DPPH) radical and 2,2′-Azino-bis(3-ethylbenzthiazoline-6-sulfonic acid (ABTS) radical being 0.14 and 0.03 mg mL-1, respectively. Our results suggested that O. aurita can be a natural source of fucoxanthin for human health and nutrition.

ContributorsXia, Song (Author) / Wang, Ke (Author) / Wan, Linglin (Author) / Li, Aifen (Author) / Hu, Qiang (Author) / Zhang, Chengwu (Author) / Julie Ann Wrigley Global Institute of Sustainability (Contributor)
Created2013-07-23
128676-Thumbnail Image.png
Description

A novel portable wireless volatile organic compound (VOC) monitoring device with disposable sensors is presented. The device is miniaturized, light, easy-to-use, and cost-effective. Different field tests have been carried out to identify the operational, analytical, and functional performance of the device and its sensors. The device was compared to a

A novel portable wireless volatile organic compound (VOC) monitoring device with disposable sensors is presented. The device is miniaturized, light, easy-to-use, and cost-effective. Different field tests have been carried out to identify the operational, analytical, and functional performance of the device and its sensors. The device was compared to a commercial photo-ionization detector, gas chromatography-mass spectrometry, and carbon monoxide detector. In addition, environmental operational conditions, such as barometric change, temperature change and wind conditions were also tested to evaluate the device performance. The multiple comparisons and tests indicate that the proposed VOC device is adequate to characterize personal exposure in many real-world scenarios and is applicable for personal daily use.

ContributorsDeng, Yue (Author) / Chen, Cheng (Author) / Xian, Xiaojun (Author) / Tsow, Francis (Author) / Verma, Gaurav (Author) / McConnell, Rob (Author) / Fruin, Scott (Author) / Tao, Nongjian (Author) / Forzani, Erica (Author) / Ira A. Fulton Schools of Engineering (Contributor)
Created2016-12-03