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

Miriam Jacome-Sosa, Qiong Hu, Camila M Manrique-Acevedo, Robert D Phair, Elizabeth J Parks, Miriam Jacome-Sosa, Qiong Hu, Camila M Manrique-Acevedo, Robert D Phair, Elizabeth J Parks

Abstract

BackgroundIt 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.MethodsThe 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.ResultsAt 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.ConclusionThese data support the concept that intestinal lipid storage may be physiologically beneficial in IS subjects.Trial registrationClinicalTrials.gov NCT02020343.FundingThis study was supported by a grant from the American Diabetes Association (grant 1-13-TS-12).

Keywords: Insulin; Lipoproteins; Metabolism.

Conflict of interest statement

Conflict of interest: The authors have declared that no conflict of interest exists.

Figures

Figure 1. Study protocol.
Figure 1. Study protocol.
The inpatient study day was preceded by a 3-day isoenergetic controlled diet. Isotope-labeled meals of identical composition were served at 12:30 pm and 6:00 pm. %En, percentage of the subject’s daily energy needs; * indicates the timing of indirect calorimetry.
Figure 2. Glucose, plasma TAG, NEFA, and…
Figure 2. Glucose, plasma TAG, NEFA, and NEFA sources in IS and IR subjects.
Values represent the mean ± SEM. Data were divided into 3 segments for analysis: 12:00 pm to 6:00 pm (post-lunch), 6:00 pm to 11:00 pm (post-dinner), and 11:00 pm to 7:00 am (nocturnal). (A) Plasma glucose and (B) triglyceride concentrations in IS (open squares) and IR (filled squares) subjects. Plasma NEFA sources are presented for subjects who were IS (C, open squares) and IR (D, filled squares), with lunch NEFAs represented by pink triangle symbols and dinner NEFAs, blue circles. P values represent comparisons between the IS and IR groups for glucose, plasma TAG, and total NEFAs for each segment (determined by repeated-measures 2-way ANOVA). For NEFA sources, *P values represent between-group comparisons for lunch and dinner NEFAs throughout the study period.
Figure 3. Dynamics of plasma insulin, apoB48,…
Figure 3. Dynamics of plasma insulin, apoB48, and dietary fat.
Values represent the mean ± SEM. (A) Plasma insulin concentrations were significantly different between the groups (2-way repeated-measures ANOVA, P values for each segment); (B) TRL-apoB48 concentrations and (C and D) total TRL-TAG (black squares) were not significantly different. Interactions among insulin, TRL-apoB48, total TRL-TAG, and subjects’ insulin sensitivity status were statistically significant during the nocturnal period (TxG P < 0.05, repeated-measures 2-way ANOVA). TRL-TAG lipid sources are presented for IS (C, open squares) and IR subjects (D, filled squares), with lunch lipid represented by pink square symbols and dinner lipid, blue squares. ^P values represent between-group comparisons for lunch and dinner throughout the study period. (E) The second-meal effect (SME) peaks, denoted with asterisks in panels C and D, were significantly different between the groups when analyzed by absolute AUC. (F) The relationship between the insulin sensitivity index (Si) and the magnitude of the SME.
Figure 4. Individual patterns of meal lipid…
Figure 4. Individual patterns of meal lipid appearance in plasma TRL-TAG.
Concentrations of TRL-TAG derived from lunch and dinner in IS and IR subjects. Pink line, TRL-TAG derived from lunch; blue line, TRL-TAG derived from dinner.
Figure 5. Meal appearance rate in plasma,…
Figure 5. Meal appearance rate in plasma, the presence of meal label, and influence of meal rates of appearance on TRL- and plasma-TAG.
Values represent the mean ± SEM. (A) IS subjects demonstrated a slower rate of appearance of dinner lipid in plasma (within-group comparison, paired, 2-tailed t test). (B) Total meal-derived lipid was higher after dinner in IR subjects (within-group comparison over time, repeated-measures 1-way ANOVA) and lower nocturnally in IS subjects. Relationships between rates of appearance of meal lipid and meal-derived TRL-TAG incremental AUC for (C) lunch and (D) dinner. Relationships between rates of appearance of meal lipid and the fasting TAG the next morning for (E) lunch and (F) dinner.
Figure 6. Influence of leptin on meal…
Figure 6. Influence of leptin on meal rates of appearance.
(A) The interaction between subjects’ insulin sensitivity status and leptin concentrations over time tended to be significant (TxG; P= 0.064). (B) IS subjects exhibited a greater change in leptin over the 19-hour period. (C) The relationship between the change in leptin over 19 hours and the ratio of dinner to lunch TRL-TAG.

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