Hepatic Metabolic Profile Reveals the Adaptive Mechanisms of Ewes to Severe Undernutrition during Late Gestation

The mechanisms underlying the adaption of liver metabolism to the undernutrition in ewes during late gestation remain unclear. This research aimed to explore the adaptive mechanisms of liver metabolism by hepatic metabolome analysis in pregnant ewes to the negative energy balance induced by severe feed restriction. Twenty ewes carrying multiple fetuses and gestating for 115 days were fed normally or restricted to a 30% feed level (10 ewes in each group) for 15 days. All ewes were sacrificed and hepatic samples were collected and analyzed by liquid chromatography-mass spectrometry. Both the principal components analysis and partial least squares of discriminant analysis of hepatic metabolites showed the clear separation between ewes in the control and severely feed-restricted groups. The metabolic profile demonstrated that the proportions of differential metabolites between the two groups in fatty acids and lipids, organic acids, and amino acids and derivatives were 61.11%, 16.67%, and 11.11%, respectively. Enriched pathways of differential metabolites were mainly involved in fatty acids and amino acids metabolism and biosynthesis. Correlation networks of differential metabolites revealed that general metabolic pattern was changed apparently and mainly based on fatty acids and lipids in the livers of feed-restricted ewes. The accumulation and oxidation of long-chain fatty acids were intensified in the livers of feed-restricted ewes, while those of medium-chain fatty acids were the opposite. In general, severe feed restriction significantly affected the levels of hepatic metabolites and altered the overall metabolic pattern. Furthermore, fatty acids oxidation as well as the utilization of amino acids and organic acids were intensified to adapt to the negative energy balance during late gestation.