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Department of Medicine, Division of Infectious Diseases and Immunology

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Biochemical Phenomena, Metabolism, and Nutrition | Cellular and Molecular Physiology | Immunology and Infectious Disease | Molecular, Genetic, and Biochemical Nutrition | Systems and Integrative Physiology


Changes in modern dietary habits such as consumption of Western-type diets affect physiology on several levels, including metabolism and inflammation. It is currently unclear whether changes in systemic metabolism due to dietary interventions are long-lasting and affect acute inflammatory processes. Here, we investigated how high-fat diet (HFD) feeding altered systemic metabolism and the metabolomic response to inflammatory stimuli. We conducted metabolomic profiling of sera collected from Ldlr(-/-) mice on either regular chow diet (CD) or HFD, and after an additional low-dose lipopolysaccharide (LPS) challenge. HFD feeding, as well as LPS treatment, elicited pronounced metabolic changes. HFD qualitatively altered the systemic metabolic response to LPS; particularly, serum concentrations of fatty acids and their metabolites varied between LPS-challenged mice on HFD or CD, respectively. To investigate whether systemic metabolic changes were sustained long-term, mice fed HFD were shifted back to CD after four weeks (HFD > CD). When shifted back to CD, serum metabolites returned to baseline levels, and so did the response to LPS. Our results imply that systemic metabolism rapidly adapts to dietary changes. The profound systemic metabolic rewiring observed in response to diet might affect immune cell reprogramming and inflammatory responses.


lipopolysaccharide (LPS), long-term metabolic rewiring, metabolomic profiling, systemic inflammation, systemic metabolism, western-type diets

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© 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (

DOI of Published Version



Lauterbach MA, Latz E, Christ A. Metabolomic Profiling Reveals Distinct and Mutual Effects of Diet and Inflammation in Shaping Systemic Metabolism in Ldlr-/- Mice. Metabolites. 2020 Aug 19;10(9):E336. doi: 10.3390/metabo10090336. PMID: 32824900. Link to article on publisher's site

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Creative Commons Attribution 4.0 License
This work is licensed under a Creative Commons Attribution 4.0 License.