A computational model of postprandial adipose tissue lipid metabolism derived using human arteriovenous stable isotope tracer data

PLoS Comput Biol. 2019 Oct 3;15(10):e1007400. doi: 10.1371/journal.pcbi.1007400. eCollection 2019 Oct.

Abstract

Given the association of disturbances in non-esterified fatty acid (NEFA) metabolism with the development of Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease, computational models of glucose-insulin dynamics have been extended to account for the interplay with NEFA. In this study, we use arteriovenous measurement across the subcutaneous adipose tissue during a mixed meal challenge test to evaluate the performance and underlying assumptions of three existing models of adipose tissue metabolism and construct a new, refined model of adipose tissue metabolism. Our model introduces new terms, explicitly accounting for the conversion of glucose to glyceraldehye-3-phosphate, the postprandial influx of glycerol into the adipose tissue, and several physiologically relevant delays in insulin signalling in order to better describe the measured adipose tissues fluxes. We then applied our refined model to human adipose tissue flux data collected before and after a diet intervention as part of the Yoyo study, to quantify the effects of caloric restriction on postprandial adipose tissue metabolism. Significant increases were observed in the model parameters describing the rate of uptake and release of both glycerol and NEFA. Additionally, decreases in the model's delay in insulin signalling parameters indicates there is an improvement in adipose tissue insulin sensitivity following caloric restriction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adipose Tissue / metabolism*
  • Arteriovenous Anastomosis / metabolism
  • Blood Glucose / metabolism
  • Computational Biology / methods*
  • Computer Simulation
  • Fatty Acids / metabolism
  • Fatty Acids, Nonesterified / metabolism
  • Glucose / metabolism
  • Humans
  • Insulin / metabolism
  • Isotopes
  • Lipid Metabolism / physiology*
  • Lipids / physiology
  • Models, Biological
  • Postprandial Period / physiology

Substances

  • Blood Glucose
  • Fatty Acids
  • Fatty Acids, Nonesterified
  • Insulin
  • Isotopes
  • Lipids
  • Glucose

Grant support

The research in this paper was supported by a grant from the Dutch Province of Limburg awarded to I.A., T.d.K, R.P, and N.v.R. The Yoyo study was supported by a grant from the Netherlands Organisation for Scientific Research TOP (grant number 200500001) awarded to M.v.B. and E.M. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.