Dietary unsaturated fat increases HDL metabolic pathways involving apoE favorable to reverse cholesterol transport

JCI Insight. 2019 Apr 4;4(7):e124620. doi: 10.1172/jci.insight.124620.


Background: HDL that contains apolipoprotein E (apoE) is a subspecies especially active in steps in reverse cholesterol transport, a process that brings cholesterol from peripheral cells to the liver. Here, we studied the effect of dietary unsaturated fat compared with carbohydrate on the metabolism of HDL containing apoE.

Methods: We enrolled 9 adults who were overweight or obese and had below-average HDL-cholesterol in a crossover study of a high-fat diet, primarily unsaturated, and a low-fat, high-carbohydrate diet. A metabolic tracer study was performed after each diet period.

Results: Dietary fat increased the secretion, metabolism, and clearance of HDL subspecies containing apoE. Dietary fat increased the rate of clearance of large cholesterol-rich HDL containing apoE and increased their conversion to small HDL containing apoE, indicating selective cholesterol ester delivery to the liver. The high-unsaturated-fat diet did not affect the metabolism of HDL lacking apoE.

Conclusion: HDL containing apoE is a diet-responsive metabolic pathway that renders HDL more biologically active in reverse cholesterol transport. This may be a mechanism by which unsaturated fat protects against coronary heart disease. Protein-based HDL subspecies such as HDL containing apoE may be used to identify additional atheroprotective treatment targets not evident in the total HDL-cholesterol measurement.

Trial registration: NCT01399632.

Funding: NIH and the National Center for Advancing Translational Science.

Keywords: Lipoproteins; Metabolism.

Publication types

  • Randomized Controlled Trial
  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Apolipoproteins E / metabolism*
  • Coronary Disease / blood
  • Coronary Disease / metabolism
  • Coronary Disease / prevention & control
  • Cross-Over Studies
  • Diet, Carbohydrate Loading / methods*
  • Diet, High-Fat / methods*
  • Dietary Fats, Unsaturated / administration & dosage*
  • Female
  • Humans
  • Lipoproteins, HDL / metabolism*
  • Male
  • Metabolic Networks and Pathways
  • Middle Aged
  • Obesity / blood
  • Obesity / complications
  • Obesity / diet therapy*
  • Obesity / metabolism
  • Treatment Outcome


  • Apolipoproteins E
  • Dietary Fats, Unsaturated
  • Lipoproteins, HDL
  • apolipoprotein E-rich HDL

Associated data