Publications (4)10.34 Total impact
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Article: Role of high-fat diet in regulation of gene expression of drug metabolizing enzymes and transporters.
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ABSTRACT: Our aim is to investigate the molecular mechanism of regulation of gene expression of drug metabolizing enzymes (DMEs) and transporters in diet-induced obesity. Adult male CD1 mice were fed diets containing 60% kcal fat (HFD) or 10% kcal fat (LFD) for 14 weeks. RNA levels of hepatic DMEs, transporters and their regulatory nuclear receptors (NRs) were analyzed by real-time PCR. Activation of cell-signaling components (JNK and NF-κΒ) and pro-inflammatory cytokines (IL-1β, IL-6 and TNFα) were measured in the liver. Finally, the pharmacodynamics of drugs metabolized by DMEs was measured to determine the clinical relevance of our findings. RNA levels of the hepatic phase I (Cyp3a11, Cyp2b10, Cyp2a4) and phase II (Ugt1a1, Sult1a1, Sultn) enzymes were reduced ~30-60% in HFD compared to LFD mice. RNA levels of Cyp2e1, Cyp1a2 and the drug transporters, multidrug resistance proteins, (Mrp)2, Mrp3 and multidrug resistant gene (Mdr)1b were unaltered in HFD mice. Gene expression of the NRs, PXR and CAR and nuclear protein levels of RXRα was reduced in HFD mice. Cytokines, JNK and NF-κΒ were induced in HFD mice. Thus reduction in hepatic gene expression in obesity may be modulated by cross-talk between NRs and inflammation-induced cell-signaling. Sleep time of Midazolam (Cyp3a substrate) was prolonged in HFD mice, while Zoxazolamine (Cyp1a2 and Cyp2e1 substrate)-induced sleep time was unaltered. This study demonstrates that gene-specific reductions in DMEs can affect specific drugs metabolized by these enzymes, thus providing a rationale to monitor the effectiveness of drug therapy in obese individuals.Life sciences 07/2011; 89(1-2):57-64. · 2.56 Impact Factor -
Article: Results of an intensive school-based weight loss program with overweight Mexican American children.
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ABSTRACT: Childhood overweight has increased significantly in the past 20 years, with the highest rates noted among Mexican Americans. Schools are an optimal setting for intervention efforts; however, few programs have demonstrated actual decreases in weight. This study evaluated an intensive school-based program designed to result in weight reduction for overweight Mexican American children. A total of 71 children (32 males, 48%) between the ages of 10 and 14 at or above the 85th percentile for body mass index (BMI) were randomized into a six-month intensive intervention (II) or self-help (SH) condition. Results revealed that children in the II condition significantly reduced their standardized BMI (zBMI) when compared with the children in the self-help condition (F(2,62)=6.58, p=0.003). The change in zBMI was significantly different at both 3 and 6 months (F(1,63)=5.74, p=0.019, F(1,63)=12.61, p=0.001, respectively) with II participants showing greater decreases in weight. The 3-month change in zBMI for the II participants was a decrease of 0.07 compared with a decrease of 0.01 for SH participants. The 6-month change in zBMI was a decrease of 0.11 for II and an increase of 0.03 for SH. Overall, the results are promising, suggesting that an intensive school-based intervention may be an effective means for promoting weight loss in overweight Mexican American children.International Journal of Pediatric Obesity 02/2007; 2(3):144-52. · 2.99 Impact Factor -
Article: Results of an intensive school-based weight loss program with overweight Mexican American children PLEASE SCROLL DOWN FOR ARTICLE
International journal of pediatric obesity: IJPO: an official journal of the International Association for the Study of Obesity 01/2007; 2:144-152. · 2.00 Impact Factor -
Article: Exercise and Toll-like receptors.
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ABSTRACT: Toll-like receptors (TLRs) are highly conserved trans-membrane proteins that play an important role in the detection and recognition of microbial pathogens. The key product of TLR signalling in antigen presenting cells is the production of inflammatory cytokines and proteins. The TLR pathway plays an important role in mediating whole body inflammation, which has been implicated in the development of chronic disease. An accumulation of chronic, low-grade inflammation is common in individuals that live a sedentary lifestyle; however, the mechanism underlying this connection is not fully understood. There is evidence to show that TLRs may be involved in the link between a sedentary lifestyle, inflammation, and disease. Recent studies have shown that both acute aerobic and chronic resistance exercise resulted in decreased monocyte cell-surface expression of TLRs. Furthermore, a period of chronic exercise training decreases both inflammatory cytokine production and the cell-surface expression of TLR4 on monocytes. These effects may contribute to post-exercise immunodepression and the reported higher susceptibility to infection in athletes. However over the long-term, a decrease in TLR expression may represent a beneficial effect because it decreases the inflammatory capacity of leukocytes, thus altering whole body chronic inflammation. The precise physiological stimulus mediating an exercise-induced decrease in cell-surface TLR expression is not known; however a number of possible signals have been implicated including anti-inflammatory cytokines, stress hormones and heat shock proteins.Exercise immunology review 02/2006; 12:34-53. · 2.79 Impact Factor
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2006
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University of Houston
- Department of Health and Human Performance
Houston, TX, USA
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