@article{3a006d881f0c4591b0db47972f3bb644,
title = "Quantifying the contribution of triglycerides to metabolic resilience through the mixed meal model",
abstract = "Despite the pivotal role played by elevated circulating triglyceride levels in the pathophysiology of cardio-metabolic diseases many of the indices used to quantify metabolic health focus on deviations in glucose and insulin alone. We present the Mixed Meal Model, a computational model describing the systemic interplay between triglycerides, free fatty acids, glucose, and insulin. We show that the Mixed Meal Model can capture deviations in the post-meal excursions of plasma glucose, insulin, and triglyceride that are indicative of features of metabolic resilience; quantifying insulin resistance and liver fat; validated by comparison to gold-standard measures. We also demonstrate that the Mixed Meal Model is generalizable, applying it to meals with diverse macro-nutrient compositions. In this way, by coupling triglycerides to the glucose-insulin system the Mixed Meal Model provides a more holistic assessment of metabolic resilience from meal response data, quantifying pre-clinical metabolic deteriorations that drive disease development in overweight and obesity.",
keywords = "ORAL GLUCOSE-TOLERANCE, FREE FATTY-ACIDS, INSULIN-RESISTANCE, ADIPOSE-TISSUE, ECTOPIC FAT, PATHOGENESIS, SECRETION, TRAFFICKING, DISEASE, OBESITY",
author = "S.D. O'Donovan and B. Erdos and D.M. Jacobs and A.J. Wanders and E.L. Thomas and J.D. Bell and M. Rundle and G. Frost and I.C.W. Arts and L.A. Afman and \{van Riel\}, N.A.W.",
note = "Funding Information: The authors would like to thank both the participants and researchers involved in the collection of data in the NutriTech and MetFlex studies. The research presented in this article was supported by a grant from the Dutch Research Council ( NWO )[ https://www.nwo.nl/ ] as part of the Complexity Programme (project number 645.001.003) with contributions from the Unilever Food Innovation Center , Wageningen, the Netherlands [ https://hive.unilever.com/ ] and Caelus Health , Amsterdam, the Netherlands [ https://caelushealth.com/ ] awarded to N.A.W.v.R., I.C.W.A., and L.A.A. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Funding Information: The authors would like to thank both the participants and researchers involved in the collection of data in the NutriTech and MetFlex studies. The research presented in this article was supported by a grant from the Dutch Research Council (NWO)[https://www.nwo.nl/] as part of the Complexity Programme (project number 645.001.003) with contributions from the Unilever Food Innovation Center, Wageningen, the Netherlands [https://hive.unilever.com/] and Caelus Health, Amsterdam, the Netherlands [https://caelushealth.com/] awarded to N.A.W.v.R. I.C.W.A. and L.A.A. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the article. Conceptualization, L.A.A, I.C.W.A, S.D.O'D, and N.A.W.v.R; methodology, B.E. S.D.O'D, and N.A.W.v.R; resources, L.A.A, J.D.B, G.F, D.M.J, M.R. E.L.T. and A.J.W; software, S.D.O'D; formal analysis, S.D.O'D; writing – original draft, S.D.O'D; writing – review \& editing, L.A.A, I.C.W.A, J.D.B. B.E, G.F. D.M.J. S.D.O'D, M.R. E.L.T. N.A.W.v.R, and A.J.W.; funding acquisition, L.A.A, I.C.W.A, and N.A.W.v.R; supervision, L.A.A, I.C.W.A, and N.A.W.v.R. SDOD, BE, ELT, JDB, MR, GF, ICWA, LAA, and NAWvR declare no conflicts of interest. DMJ and AJW are employees of Unilever, which manufactures and markets consumer food products. Publisher Copyright: {\textcopyright} 2022 The Authors",
year = "2022",
month = nov,
day = "18",
doi = "10.1016/j.isci.2022.105206",
language = "English",
volume = "25",
journal = "iScience",
issn = "2589-0042",
publisher = "Elsevier Inc.",
number = "11",
}