Dietary lipid structure in early life does not program fat absorption in later life
Authors: Ronda Onne , Havinga Rick , van de Heijning Bert , Kuipers Folkert , Verkade Henkjan 
Published: June 2021

Objectives and studyPreviously, we reported that feeding mice in early life with the experimental infant milk formula Nuturis® (eIMF) with a lipid structure more similar to human milk, i.e. with large (3–5 μm) lipid globules coated with milk phospholipids, resulted in a lower body weight and fat mass gain when challenged with a Western style diet later in life, compared to standard, control IMF (cIMF; Ped Res 72:362; 2012). The mechanism by which eIMF exerts this effect has remained unclear. It is known from literature that lipid uptake kinetics can be important, for example by determining the metabolic fate of absorbed lipids (storage versus oxidation). In this study, we tested the hypothesis that eIMF feeding in early life permanently affects the kinetics of fat absorption in mice.MethodsWe fed male, pair‐housed C57BL/6JOlaHsd mice a rodent diet comprising cIMF or eIMF from postnatal day 16 to 42, followed by 3 weeks of a regular rodent diet (AIN‐93G). At postnatal day 63, upon intraperitoneal injection of the lipoprotein lipase inhibitor poloxamer‐407, fasting mice were administered a lipid bolus containing labeled fat (2H‐oleic acid and tri‐1‐13C‐olein) by gavage. We analyzed plasma lipids and appearance of 13C‐ and 2H‐labeled lipids in blood samples taken at 0, 1, 2, 3 and 5 h after administration using gas chromatography‐mass spectrometry. Values are given in means ± SD.ResultsIn the eIMF and cIMF groups total plasma fatty acids/acyl chains increased similarly over the 5h course of the experiment: from 9±3 to 99±41 mM in cIMF and from 9±4 to 82±36 mM in eIMF, resulting in similar areas under the curve: 252±91 and 221±81 mM·h, respectively. Total plasma fatty acids/acyl chain increase rate between 1 and 3 h after gavage was 22±9 and 20±7 mM·h−1 for cIMF and eIMF, respectively, indicating similar uptake rates from the intestine. The plasma appearances of 2H‐ and 13C‐oleic acid were similar within and between groups. Interestingly, the plasma fat uptake kinetics between the two mice housed in pairs varied by at least a factor two in 10 out of 11 pairs, irrespective of being fed cIMF or eIMF in early life (p<0.001).ConclusionOur data in mice indicate that exposure early in life to dietary fat in the form of larger lipid globules covered with milk phospholipids (Nuturis®) does not affect the kinetics of intestinal fat digestion and absorption later in life. The twofold difference found in fat uptake kinetics between pair‐housed mice now warrants experiments to address whether this translates into different metabolic profiles and sensitivities later in life.Support or Funding InformationDisclosure of interests: The present study was funded by Nutricia Research. BJMvdH is employed by Nutricia Research. HJV is a consultant for Nutricia Research outside the submitted work, for which his institution is financially compensated.This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.