iScience (Nov 2022)

Quantifying the contribution of triglycerides to metabolic resilience through the mixed meal model

  • Shauna D. O’Donovan,
  • Balázs Erdős,
  • Doris M. Jacobs,
  • Anne J. Wanders,
  • E. Louise Thomas,
  • Jimmy D. Bell,
  • Milena Rundle,
  • Gary Frost,
  • Ilja C.W. Arts,
  • Lydia A. Afman,
  • Natal A.W. van Riel

Journal volume & issue
Vol. 25, no. 11
p. 105206

Abstract

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Summary: 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.

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