Metabolomic changes in severe acute malnutrition suggest hepatic oxidative stress: a secondary analysis.

Abstract

Severe acute malnutrition (SAM), due to poor energy and/or protein intake, is associated with poor growth, depressed immune function, and long-term impacts on metabolic function. As the liver is a major metabolic organ and malnutrition poses metabolic stress, we hypothesize that SAM will be associated with alterations in the hepatic metabolome reflective of oxidative stress, gluconeogenesis, and ketogenesis. Thus, the purpose of this secondary analysis was to understand how SAM alters hepatic metabolism using a piglet model. Weanling piglets were feed either a reference (REF) or protein-energy deficient diet (MAL) for 5 weeks. After dietary treatment MAL piglets were severely underweight (weight-for-age Z-score of -3.29, Welch's t test, P = .0007), moderately wasted (weight-for-length Z-score of-2.49, Welch's t test, P = .003), and tended toward higher hepatic triglyceride content (Welch's t test, P = .07). Hematologic and blood biochemical measurements were assessed at baseline and after dietary treatment. The hepatic metabolome was investigated using 1H-NMR spectroscopy. Hepatic concentrations of betaine, cysteine, and glutathione tended to be lower in MAL (Welch's t test with FDR correction, P < .1), while inosine, lactate, and methionine sulfoxide concentrations were higher in MAL (inosine: P = .0448, lactate: P = .0258, methionine sulfoxide: P = .0337). These changes suggest that SAM is associated with elevated hepatic oxidative stress, increased gluconeogenesis, and alterations in 1-carbon metabolism.

• Authors: Mariana Parenti, Shannon McClorry, Elizabeth A Maga, Carolyn M Slupsky
• Journal: Nutrition research (New York, N.Y.) (Nutr Res) Vol. 91 Pg. 44-56 (07 2021) ISSN: 1879-0739 [Electronic] United States
• PMID: 34134040 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
• Copyright: Copyright © 2021. Published by Elsevier Inc.

Chemical References

• Triglycerides
• Lactic Acid
• Betaine
• Inosine
• Methionine
• Glutathione
• Cysteine
• Safrole
• sulfoxide
• methionine sulfoxide

Topics

• Animals
• Betaine (metabolism)
• Cysteine (metabolism)
• Diet
• Gluconeogenesis
• Glutathione (metabolism)
• Inosine (metabolism)
• Lactic Acid (metabolism)
• Liver (metabolism)
• Male
• Metabolome
• Metabolomics (methods)
• Methionine (analogs & derivatives, metabolism)
• Oxidative Stress
• Safrole (analogs & derivatives, metabolism)
• Severe Acute Malnutrition (complications, metabolism)
• Swine
• Thinness
• Triglycerides