Immune and metabolic responses in early and late sepsis during mild dietary zinc restriction

Crowell, Kristen T.; Phillips, Brett E.; Kelleher, Shannon L.; Soybel, David I.; Lang, Charles H.

doi:10.1016/j.jss.2016.10.020

Cited by 6 publications

(4 citation statements)

References 48 publications

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“…To investigate the systemic consequences of sepsis, we first measured food intake up to 30 hours after induction of CLP using metabolic chambers. In line with previous findings ( 25 , 26 ), food intake was significantly reduced in response to polymicrobial infection compared with the sham control ( Figure 1A ). We next performed unbiased global metabolomics on plasma of control and septic mice at 30 hours after CLP in alignment with our previous studies of the tissue tolerance phenotype of sepsis ( 13 , 24 ) by ultrahigh-performance liquid chromatography–tandem mass spectroscopy (UPLC-MS/MS).…”

Section: Resultssupporting

confidence: 93%

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Oh¹,

Zabalawi²,

Jain³

et al. 2022

JCI Insight

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Section: Resultssupporting

confidence: 93%

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Oh¹,

Zabalawi²,

Jain³

et al. 2022

JCI Insight

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“…In line with previous findings (25,26), food intake was significantly reduced in response to polymicrobial infection compared to the sham control (Fig. 1A).…”

Section: Sepsis Shifts Fuel Utilization and Reduces Systemic Energy Expendituresupporting

confidence: 93%

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Zabalwi

Jain

et al. 2021

Preprint

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Sepsis is a life-threatening organ dysfunction by dysregulated host response to an infection. The metabolic aberrations associated with sepsis underly an acute and organism wide hyper-inflammatory response and multiple organ dysfunction; however, crosstalk between systemic metabolomic alterations and metabolic reprograming at organ levels remains unknown. We analyzed substrate utilization by the respiratory exchange ratio, energy expenditure, metabolomic screening and transcriptional profiling in a cecal ligation and puncture (CLP) model, to show that sepsis increases circulating free fatty acids and acylcarnitines but decreases levels of amino acids and carbohydrates leading to a drastic shift in systemic fuel preference. Comparative analysis of previously published metabolomics from septic liver indicates a positive correlation with hepatic and plasma metabolites during sepsis. In particular, glycine deficiency was a common abnormality of both plasma and the liver during sepsis. Interrogation of the hepatic transcriptome in septic mice suggests that the septic liver may contribute to systemic glycine deficiency by downregulating genes involved in glycine synthesis. Interestingly, intraperitoneal injection of the pyruvate dehydrogenase kinase (PDK) inhibitor dichloroacetate (DCA) reverses sepsis-induced anorexia, energy imbalance, dyslipidemia, hypoglycemia, and glycine deficiency. Collectively, our data indicate that PDK inhibition rescues systemic energy imbalance and metabolic dysfunction in sepsis partly through restoration of hepatic fuel metabolism.

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“…up to seven days post-sepsis. We incorporated an established a seven day model of late sepsis, cecal ligation and puncture (CLP) (Crowell, Phillips, Kelleher, Soybel, & Lang, 2017;Vachharajani et al, 2014;X. Wang et al, 2016).…”

Section: Introductionmentioning

confidence: 99%

Loss of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels is coupled to persistent neuroinflammation and behavioral deficits in late sepsis

Nwafor

Chakraborty

Brichacek

et al. 2020

Brain, Behavior, and Immunity

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Sepsis is a host response to systemic inflammation and infection that may lead to multi-organ dysfunction and eventual death. While acute brain dysfunction is common among all sepsis patients, chronic neurological impairment is prevalent among sepsis survivors. The brain microvasculature has emerged as a major determinant of sepsis-associated brain dysfunction, yet the mechanisms that underlie its associated neuroimmune perturbations and behavioral deficits are not well understood. An emerging body of data suggests that inhibition of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels may be associated with changes in endothelial cell barrier integrity. The objective of this study was to elucidate the connection between alterations in cerebrovascular TNAP enzyme activity and brain microvascular dysfunction in late sepsis. We hypothesized that the disruption of TNAP enzymatic activity in cerebral microvessels would be coupled to the sustained loss of brain microvascular integrity, *

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Immune and metabolic responses in early and late sepsis during mild dietary zinc restriction

Cited by 6 publications

References 48 publications

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Dichloroacetate improves systemic energy balance and feeding behavior during sepsis

Loss of tissue-nonspecific alkaline phosphatase (TNAP) enzyme activity in cerebral microvessels is coupled to persistent neuroinflammation and behavioral deficits in late sepsis

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