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The Undernourished Neonatal Mouse Metabolome Reveals Evidence of Liver and Biliary Dysfunction, Inflammation, and Oxidative Stress 1–3

Overview of attention for article published in Journal of Nutrition, December 2013
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Title
The Undernourished Neonatal Mouse Metabolome Reveals Evidence of Liver and Biliary Dysfunction, Inflammation, and Oxidative Stress 1–3
Published in
Journal of Nutrition, December 2013
DOI 10.3945/jn.113.183731
Pubmed ID
Authors

Geoffrey A. Preidis, Mignon A. Keaton, Philippe M. Campeau, Brooke C. Bessard, Margaret E. Conner, Peter J. Hotez

Abstract

Undernutrition contributes to half of all childhood deaths under the age of 5 y, and confers upon survivors a life-long predisposition to obesity, type 2 diabetes, and cardiovascular disease. Mechanisms underlying the link between early nutrient deprivation and noncommunicable diseases are unknown. Using outbred CD1 neonatal mice, we measured metabolic profile differences between conventionally reared mice given unrestricted access to nursing, the control group, and undernourished mice subjected to protein-calorie deprivation through timed separation from lactating mothers. After 11 d of undernutrition, urine, plasma, liver, ileal fluid, cecal fluid, and stool were harvested from 8 pools of 4 neonatal mice per group. The metabolome was identified using a multiplatform mass spectrometry-based approach, and random forest metrics were used to identify the most important metabolites that distinguished the undernourished from the control group. Our data reveal striking metabolic changes in undernourished mice consistent with the known mammalian response to starvation, including evidence of muscle and fat catabolism and increased reliance on the tricarboxylic acid cycle for energy. However, we also revealed evidence of liver and biliary injury, anomalies in bile acid metabolism, oxidative stress and inflammation, accelerated heme breakdown, and altered regulation of DNA methylation. Among the metabolites that most strongly distinguished the 2 groups were 2-hydroxyisobutyrate, increased 3-fold in plasma of undernourished mice (P = 2.19 × 10(-11)); urobilinogen, increased 11-fold in urine of undernourished mice (P = 4.22 × 10(-7)); deoxycholate, decreased 94% in stool of undernourished mice (P = 3.0 × 10(-4)); and 12 different products of the enzyme γ-glutamyltransferase, increased in all 6 compartments of undernourished mice. This model of the undernourished neonatal metabolome illustrates the wide range of pathways disrupted by undernutrition in early development, and suggests mechanistic links between early starvation and persistent metabolic diseases.

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Mendeley readers

Mendeley readers

The data shown below were compiled from readership statistics for 104 Mendeley readers of this research output. Click here to see the associated Mendeley record.

Geographical breakdown

Country Count As %
United States 2 2%
Japan 1 <1%
Unknown 101 97%

Demographic breakdown

Readers by professional status Count As %
Researcher 23 22%
Student > Ph. D. Student 20 19%
Student > Master 15 14%
Student > Doctoral Student 6 6%
Professor > Associate Professor 6 6%
Other 14 13%
Unknown 20 19%
Readers by discipline Count As %
Medicine and Dentistry 26 25%
Agricultural and Biological Sciences 24 23%
Biochemistry, Genetics and Molecular Biology 10 10%
Nursing and Health Professions 5 5%
Sports and Recreations 3 3%
Other 10 10%
Unknown 26 25%
Attention Score in Context

Attention Score in Context

This research output has an Altmetric Attention Score of 1. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 21 February 2014.
All research outputs
#20,653,708
of 25,371,288 outputs
Outputs from Journal of Nutrition
#8,898
of 9,882 outputs
Outputs of similar age
#242,864
of 318,810 outputs
Outputs of similar age from Journal of Nutrition
#54
of 58 outputs
Altmetric has tracked 25,371,288 research outputs across all sources so far. This one is in the 10th percentile – i.e., 10% of other outputs scored the same or lower than it.
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We're also able to compare this research output to 58 others from the same source and published within six weeks on either side of this one. This one is in the 1st percentile – i.e., 1% of its contemporaries scored the same or lower than it.