Effects of Dehydroepiandrosterone Administration on Rat Hepatic Metabolism Following Thermal Injury

Banta, Scott; Yokoyama, Toshiharu; Berthiaume, François; Yarmush, Martin L.

doi:10.1016/j.jss.2005.01.001

Cited by 25 publications

(45 citation statements)

References 61 publications

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“…This quantity changed linearly with time, indicating that the perfused liver was metabolically stable for the duration of the perfusion. This was also observed in prior studies (Arai et al, 2001;Banta et al, 2005;Lee et al, 2000Lee et al, , 2003. The slope was determined to obtain the rate of production or consumption of each metabolite and the results are tabulated in Table I. O 2 and CO 2 outputs (reaction numbers 55 and 56) were not measured.…”

Section: Animal Model and Liver Perfusionsmentioning

confidence: 81%

“…A range has to be assigned for O 2 and CO 2 external fluxes; otherwise physiologically irrelevant flux distribution could be obtained. Based on previous perfused liver studies (Arai et al, 2001;Banta et al, 2005Banta et al, , 2007Lee et al, 2000Lee et al, , 2003, a wide range (between 50-350 mmol/ g liver/h) is attributed to oxygen uptake and carbon dioxide output for both states.…”

Section: Animal Model and Liver Perfusionsmentioning

confidence: 98%

“…Isolated perfused liver systems have been extensively used to characterize the detailed metabolic changes in various abnormal metabolic conditions, for example systemic burns and trauma, infection, and other insults (Arai et al, 2001;Banta et al, 2005Banta et al, , 2007Lee et al, 2000Lee et al, , 2003Yokoyama et al, 2005). A critical component of these investigations is to evaluate the impact of these insults on glucose and nitrogen metabolism since one of the major functions of the liver is to maintain physiological circulating glucose and ammonia levels.…”

Section: Introductionmentioning

confidence: 99%

“…A caveat of this approach is that fasting induces metabolic changes that superpose to disease-related changes. In some instances, a different metabolic model was used for the fed state, and both the fed and fasted models were fitted to the data; the best fitting model was then used to derive the fluxes (Arai et al, 2001;Banta et al, 2005Banta et al, , 2007Lee et al, 2000Lee et al, , 2003Yokoyama et al, 2005). This implied that the glycolytic and gluconegenic states are mutually exclusive.…”

Section: Introductionmentioning

confidence: 99%

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Metabolic flux determination in perfused livers by mass balance analysis: Effect of fasting

Orman

Arai

Yarmush

et al. 2010

Biotech & Bioengineering

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Isolated perfused livers from fasted rats have been extensively studied to understand the underlying mechanisms of injury-induced acute and chronic changes in liver metabolism. In this study, we investigated the impact of fasting on perfused liver metabolism. The methodology we used combines a flux variability approach, sampling analysis and singular value decomposition (SVD) to analyze the data using the same metabolic reaction network for both fed and fasted livers. Considering both experimental observations and mathematical analysis, the results show that 24 h fasting results in a limited glucose production from glycogen and up-regulation of gluconeogenic pathway. Glutamate metabolism and fatty acid oxidation are also slightly up-regulated whereas aspartate metabolism is down-regulated after fasting. Moreover, SVD analysis elucidates that glycogen breakdown mainly affects the pentose phosphate pathway in fasted state whereas co-occurrence pattern associated with glycogen breakdown and glycolysis observed in flux samples of fed state is dominant. In conclusion, this analysis provides a detailed description of the metabolic changes in two different states, considering the entire steady state flux space and dominant flux patterns that capture the system variations within the flux space.

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Section: Animal Model and Liver Perfusionsmentioning

confidence: 81%

Section: Animal Model and Liver Perfusionsmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Metabolic flux determination in perfused livers by mass balance analysis: Effect of fasting

Orman

Arai

Yarmush

et al. 2010

Biotech & Bioengineering

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“…NO derived from iNOS has been implicated in many pathological events (5,20,33) and in the development of tissue injury (28). Nonetheless, the precise role of NO in different physiological functions after injury is not entirely clear because most of the previous studies utilized nonspecific NOS inhibitors (9,39).…”

Section: Discussionmentioning

confidence: 99%

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury

Kan

Hsu

Schwacha

et al. 2008

Journal of Applied Physiology

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Contribution of gene expression to metabolic fluxes in hypermetabolic livers induced through burn injury and cecal ligation and puncture in rats

Banta

Vemula

Yokoyama

et al. 2006

Biotech & Bioengineering

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Severe injury activates many stress-related and inflammatory pathways that can lead to a systemic hypermetabolic state. Prior studies using perfused hypermetabolic rat livers have identified intrinsic metabolic flux changes that were not dependent upon the continual presence of elevated stress hormones and substrate loads. We investigated the hypothesis that such changes may be due to persistent alterations in gene expression. A systemic hypermetabolic response was induced in rats by applying a moderate burn injury followed 2 days later by cecum ligation and puncture (CLP) to produce sepsis. Control animals received a sham-burn followed by CLP, or a sham-burn followed by sham-CLP. Two days after CLP, livers were analyzed for gene expression changes using DNA microarrays and for metabolism alterations by ex vivo perfusion coupled with Metabolic Flux Analysis. Burn injury prior to CLP increased fluxes while decreases in gene expression levels were observed. Conversely, CLP alone significantly increased metabolic gene expression, but decreased many of the corresponding metabolic fluxes. Burn injury combined with CLP led to the most dramatic changes, where concurrent changes in fluxes and gene expression levels occurred in about 1/3 of the reactions. The data are consistent with the notion that in this model, burn injury prior to CLP increased fluxes through post-translational mechanisms with little contribution of gene expression, while CLP treatment up-regulated the metabolic machinery by transcriptional mechanisms. Overall, these data show that mRNA changes measured at a single time point by DNA microarray analysis do not reliably predict metabolic flux changes in perfused livers.

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Effects of Dehydroepiandrosterone Administration on Rat Hepatic Metabolism Following Thermal Injury

Cited by 25 publications

References 61 publications

Metabolic flux determination in perfused livers by mass balance analysis: Effect of fasting

Metabolic flux determination in perfused livers by mass balance analysis: Effect of fasting

Selective inhibition of iNOS attenuates trauma-hemorrhage/resuscitation-induced hepatic injury

Contribution of gene expression to metabolic fluxes in hypermetabolic livers induced through burn injury and cecal ligation and puncture in rats

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