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5. Transcription profiling in rat liver in response to dietary docosahexaenoic acid implicates stearoyl-coenzyme a desaturase as a nutritional target for lipid lowering

Author

Kramer, Jeffrey A., LeDeaux, John, Butteiger, Dustie, Young, Tracy, Crankshaw, Carolyn, Harlow, Harry, Kier, Larry, and Bhat, B. Ganesh

Subjects
Gene expression -- Physiological aspects, Cholesterol metabolism -- Genetic aspects, Genetic transcription -- Physiological aspects, Omega-3 fatty acids -- Physiological aspects, Food/cooking/nutrition
Abstract

The gene expression profile in response to dietary docosahexaenoic acid rich oil for 6 wk was analyzed in the livers of male Sprague-Dawley rats to identify genes whose expression was regulated by dietary modification and correlated with serum lipid changes. Such genes may represent targets for intervention into cardiovascular health using nutraceuticals. High density glass microarrays containing ~7800 cloned expressed sequences from rat were used to identify those genes that responded to dietary long chain (n-3) fatty acids. In general, dietary long chain (n-3) fatty acids exhibited statistically significant lipid-lowering effects similar to a pharmaceutical alternative, fenofibrate, but showed narrower effects on the transcription of most of the genes assayed. The transcription patterns confirmed that the expression of several key genes involved in cholesterol metabolism, fatty acid [beta]-oxidation and lipogenesis was affected. These analyses indicated that stearoyl-coenzyme A ([DELTA]9) desaturase, a key enzyme involved in the regulation of triglyceride biosynthesis and secretion, is a potential target for nutritional intervention for hyperlipidemia and cardiovascular health. In addition these results suggested that regulation of the farnesoid X receptor may be a key nutritionally regulated mediator of serum lipid changes. A nutritional product concept based on a convenient dietary aid demonstrated comparable efficacy with less spurious gene regulation than a pharmaceutical alternative. KEY WORDS: * (n-3) fatty acids * nutraceuticals * cardiovascular * gene transcription

Published
2003

9. A review of the carcinogenic potential of glyphosate by four independent expert panels and comparison to the IARC assessment

Author

Williams, Gary M., primary, Aardema, Marilyn, additional, Acquavella, John, additional, Berry, Sir Colin, additional, Brusick, David, additional, Burns, Michele M., additional, de Camargo, Joao Lauro Viana, additional, Garabrant, David, additional, Greim, Helmut A., additional, Kier, Larry D., additional, Kirkland, David J., additional, Marsh, Gary, additional, Solomon, Keith R., additional, Sorahan, Tom, additional, Roberts, Ashley, additional, and Weed, Douglas L., additional

Published
2016
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14. Applications of microarrays with toxicologically relevant genes (tox genes) for the evaluation of chemical toxicants in Sprague Dawley rats in vivo and human hepatocytes in vitro

Author

Kier, Larry D, primary, Neft, Robin, additional, Tang, Lei, additional, Suizu, Robert, additional, Cook, Tari, additional, Onsurez, Kathy, additional, Tiegler, Karen, additional, Sakai, Yumiko, additional, Ortiz, Michael, additional, Nolan, Tim, additional, Sankar, Usha, additional, and Li, Albert P, additional

Published
2004
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21. Male fertility study on N,N-dimethylacetamide administered by the inhalation route to sprague-dawley rats

Author

Wang, G. M., Kier, Larry, and Pounds, George

Abstract

Male Sprague-Dawley rats were exposed to N,N-dimethylacetamide (DMAC) and mated to untreated virgin females. Mean analytical exposure concentrations were 40, 116, and 386 ppm, respectively. A control group was exposed to air containing no DMAC. A total of 69 d of exposure to DMAC at these levels produced treatment-related effects of increased liver weights and liver/body weight ratios in the high- and medium-exposure groups of male rats. Reproductive data indicated no treatment-related effects on copulation efficiency or efficiency in effecting pregnancy, and there were no detectable treatment-related effects on preimplantation loss, postimplantation loss, embryotoxicity, or fetotoxicity in litters of females mated to males exposed to DMAC at the levels used in this study. The significance of these findings is discussed.

Published
1989
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25. Acute myelogenous leukemia.

Author

IRELAND, BELINDA K., ACQUAVELLA, JOHN F., KIER, LARRY D., Ireland, B K, Acquavella, J F, and Kier, L D

Published
1993

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