Human intestinal lipid storage through sequential meals reveals faster dinner appearance is associated with hyperlipidemia

BACKGROUND: It is increasingly recognized that intestinal cells can store lipids after a meal, yet the effect of this phenomenon on lipid absorption patterns in insulin resistance remains unknown. METHODS: The kinetics of meal fat appearance were measured in insulin-sensitive (IS, n = 8) and insulin-resistant (IR, n = 8) subjects after sequential, isotopically labeled lunch and dinner meals. Plasma dynamics on triacylglycerol-rich (TAG-rich) lipoproteins and plasma hormones were analyzed using a nonlinear, non–steady state kinetic model. RESULTS: At the onset of dinner, IS subjects showed an abrupt plasma appearance of lunch lipid consistent with the “second-meal effect,” followed by slower appearance of dinner fat in plasma, resulting in reduced accumulation of dinner TAG of 48% compared with lunch. By contrast, IR subjects exhibited faster meal TAG appearance rates after both lunch and dinner. This effect of lower enterocyte storage between meals was associated with greater nocturnal and next-morning hyperlipidemia. The biochemical data and the kinetic analysis of second-meal effect dynamics are consistent with rapid secretion of stored TAG bypassing lipolysis and resynthesis. In addition, the data are consistent with a role for the diurnal pattern of plasma leptin in regulating the processing of dietary lipid. CONCLUSION: These data support the concept that intestinal lipid storage may be physiologically beneficial in IS subjects. TRIAL REGISTRATION: ClinicalTrials.gov NCT02020343. FUNDING: This study was supported by a grant from the American Diabetes Association (grant 1-13-TS-12).