An integrative model of cardiometabolic traits identifies two types of metabolic syndrome

Human diseases arise in a complex ecosystem composed of disease mechanisms and the whole-body state. However, the precise nature of the whole-body state and its relations with disease remain obscure. Here we map similarities among clinical parameters in normal physiological settings, including a lar...

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Bibliographic Details
Published in:	eLife Vol. 10
Main Authors:	Frishberg, Amit, van den Munckhof, Inge, Ter Horst, Rob, Schraa, Kiki, Joosten, Leo Ab, Rutten, Joost Hw, Iancu, Adrian C, Dregoesc, Ioana M, Tigu, Bogdan A, Netea, Mihai G, Riksen, Niels P, Gat-Viks, Irit
Format:	Journal Article
Language:	English
Published:	England eLife Science Publications, Ltd 28-01-2021 eLife Sciences Publications Ltd eLife Sciences Publications, Ltd
Subjects:	Adult Aged Analysis Blood lipids Body mass index cardiometabolic disease Cardiovascular Diseases - epidemiology Cardiovascular Diseases - metabolism Cholesterol Computational and Systems Biology computational modeling Cytokines Disease Female High density lipoprotein Humans Immunology Lipoproteins Male Medical diagnosis Medicine Metabolic syndrome Metabolic Syndrome - classification Metabolic Syndrome - epidemiology Metabolites Middle Aged multi-omics data Obesity phenotypic states Physiological aspects Physiology Risk Factors Young Adult computational biology metabolic syndrome systems biology multi-omics data cardiometabolic disease medicine computational modeling human phenotypic states
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Summary:	Human diseases arise in a complex ecosystem composed of disease mechanisms and the whole-body state. However, the precise nature of the whole-body state and its relations with disease remain obscure. Here we map similarities among clinical parameters in normal physiological settings, including a large collection of metabolic, hemodynamic, and immune parameters, and then use the mapping to dissect phenotypic states. We find that the whole-body state is faithfully represented by a quantitative two-dimensional model. One component of the whole-body state represents 'metabolic syndrome' (MetS) - a conventional way to determine the cardiometabolic state. The second component is decoupled from the classical MetS, suggesting a novel 'non-classical MetS' that is characterized by dozens of parameters, including dysregulated lipoprotein parameters (e.g. low free cholesterol in small high-density lipoproteins) and attenuated cytokine responses of immune cells to ex vivo stimulations. Both components are associated with disease, but differ in their particular associations, thus opening new avenues for improved personalized diagnosis and treatment. These results provide a practical paradigm to describe whole-body states and to dissect complex disease within the ecosystem of the human body.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work. These authors also contributed equally to this work.
ISSN:	2050-084X 2050-084X
DOI:	10.7554/eLife.61710