Acetyl-CoA from inflammation-induced fatty acids oxidation promotes hepatic malate-aspartate shuttle activity and glycolysis

American Journal of Physiology. Endocrinology and Metabolism
Tongxin WangFeiruo Huang

Abstract

Hepatic metabolic syndrome is associated with inflammation, as inflammation stimulates the reprogramming of nutrient metabolism and hepatic mitochondria-generated acetyl-CoA, but how acetyl-CoA affects the reprogramming of nutrient metabolism, especially glucose and fatty acids, in the condition of inflammation is still unclear. Here, we used an acute inflammation model in which pigs were injected with lipopolysaccharide (LPS) and found that hepatic glycolysis and fatty acid oxidation are both promoted. Acetyl-proteome profiling of LPS-infected pigs liver showed that inflammatory stress exacerbates the acetylation of mitochondrial proteins. Both mitochondrial glutamate oxaloacetate transaminase 2 (GOT2) and malate dehydrogenase 2 (MDH2) were acetylated, and the malate-aspartate shuttle (MAS) activity was stimulated to maintain glycolysis. With the use of 13C-carbon tracing in vitro, acetyl-CoA was found to be mainly supplied by lipid-derived fatty acid oxidation rather than glucose-derived pyruvate oxidative decarboxylation, while glucose was mainly used for lactate production in response to inflammatory stress. The results of the mitochondrial experiment showed that acetyl-CoA directly increases MDH2 and, in turn, the GOT2 ace...Continue Reading

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Citations

Apr 12, 2020·Experimental Biology and Medicine·Hang YangZhaocai Zhang
Aug 17, 2019·Nutrition in Clinical Practice : Official Publication of the American Society for Parenteral and Enteral Nutrition·Amy K WiseKeith R Miller
Jun 18, 2020·Frontiers in Oncology·Meiliang LiuXiaoyun Zeng
Sep 25, 2020·The British Journal of Nutrition·Weilei YaoFeiruo Huang
Nov 5, 2021·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ryan P MendozaJared M Brown

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Methods Mentioned

BETA
acetylation
transfection
Protein Assay
immunoprecipitation
Assay

Software Mentioned

MaxQuant
Andromeda

Related Concepts