Impact of Intended Isocaloric Early vs. Late Time-Restricted Eating on Plasma Lipidome in Women with Overweight or Obesity: Secondary Analysis of the ChronoFast Trial

Abstract Time-restricted eating (TRE) is a promising strategy to prevent obesity and type 2 diabetes, but its effects on lipid metabolism remain controversial. The aim of the present research is to assess and compare the impact of isocaloric early (eTRE) vs. late (lTRE) TRE on the plasma lipidomic profile. This randomized crossover study examines 31 women with overweight or obesity who follow a two-week eTRE and a two-week lTRE in an intended isocaloric setting. Blood plasma and subcutaneous adipose tissue biopsies are analyzed using shotgun lipidomics and transcriptomics, respectively. Between interventions and within the lTRE, lipid species and classes, as well as enzyme activity indices, are not substantially changed. Within the eTRE, changes are observed for 103 lipid species, including a reduction of ceramide and phosphatidylcholine classes, and for the desaturation indices D5D, D6D, and D9D, as well as elongation index ELOVL6. Combined analysis of plasma lipidome and adipose tissue reveals alterations in the glycerophospholipid pathway and in the expression of phospholipase enzymes PLB1, PLA2G6, and PLAG4B, dependent on TRE timing. These results suggest that eating timing during TRE might be crucial for remodeling the plasma lipidome and adipose tissue transcriptome and highlight the need of future lipidomic research in TRE.