Dietary Fat Intake Modifies the Effect of a Common Variant in the LIPC Gene on Changes in Serum Lipid Concentrations during a Long-Term Weight-Loss Intervention Trial

J Nutr. 2015 Jun;145(6):1289-94. doi: 10.3945/jn.115.212514. Epub 2015 Apr 29.


Background: Hepatic lipase (HL) plays a pivotal role in the metabolism of HDL and LDL. Recent genome-wide association studies have identified common variants in the HL gene (LIPC) associated with HDL cholesterol.

Objective: We tested the effect of a common variant in LIPC on changes in blood lipids in response to weight-loss diets in the Preventing Overweight Using Novel Dietary Strategies Trial.

Methods: We genotyped LIPC rs2070895 in 743 overweight or obese adults aged 30-70 y (61% women) who were assigned to high-fat (40% energy) or low-fat (20% energy) diets for 2 y. We measured serum concentrations of total cholesterol (TC), triglycerides, LDL cholesterol, and HDL cholesterol at baseline and 2 y of intervention.

Results: At 2 y of intervention, dietary fat modified effects of the variant on changes in serum TC, LDL cholesterol, and HDL cholesterol (P-interaction: 0.0008, 0.004, and 0.03, respectively). In the low-fat group, as compared to the G allele, the A allele tended to be related to the decrease in TC and LDL cholesterol concentrations [TC (β ± SE): -5.5 ± 3.0, P = 0.07; LDL cholesterol: -4.8 ± 2.5, P = 0.06] and a lower increase in HDL cholesterol concentrations (β ± SE: -1.37 ± 0.69, P = 0.048), whereas an opposite effect in the high-fat diet group was evident [TC (β ± SE): 7.3 ± 2.7, P = 0.008; LDL cholesterol: 4.1 ± 2.3, P = 0.07], and there was no genetic effect on changes in HDL cholesterol concentrations (P = 0.54).

Conclusion: Dietary fat intake modifies the effect of a common variant in LIPC on changes in serum lipids during a long-term weight-loss intervention in overweight or obese adults. This trial was registered at as NCT00072995.

Keywords: LIPC; gene-diet interaction; hepatic lipase; high-fat diet; weight-loss intervention.

Publication types

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

MeSH terms

  • Adult
  • Aged
  • Body Mass Index
  • Cholesterol, HDL / blood*
  • Cholesterol, LDL / blood*
  • Diet, High-Fat
  • Diet, Reducing*
  • Dietary Fats / administration & dosage*
  • Female
  • Genome-Wide Association Study
  • Genotyping Techniques
  • Humans
  • Linear Models
  • Lipase / genetics*
  • Male
  • Middle Aged
  • Obesity / diet therapy
  • Obesity / genetics
  • Overweight / diet therapy
  • Overweight / genetics
  • Polymorphism, Single Nucleotide
  • Triglycerides / blood*
  • Weight Loss


  • Cholesterol, HDL
  • Cholesterol, LDL
  • Dietary Fats
  • Triglycerides
  • LIPH protein, human
  • Lipase

Associated data