Abstract

We recently reported that feeding mice in their early life a diet containing a lipid structure more similar to human milk (eIMF, Nuturis) results in lower body weights and fat mass gain upon high fat feeding in later life, compared to control (cIMF). To understand the underlying mechanisms, we now explored parameters possibly involved in this long-term effect. Male C57BL/6JOlaHsd mice, fed rodent diets containing eIMF or cIMF from postnatal (PN) day 16–42, were sacrificed at PN42. Hepatic proteins were measured using targeted proteomics. Lipids were assessed by LC–MS/MS (acylcarnitines) and GC-FID (fatty-acyl chain profiles). Early life growth and body composition, cytokines, and parameters of bile acid metabolism were similar between the groups. Hepatic concentrations of multiple proteins involved in β-oxidation (+ 17%) the TCA cycle (+ 15%) and mitochondrial antioxidative proteins (+ 28%) were significantly higher in eIMF versus cIMF-fed mice (p < 0.05). Hepatic l-carnitine levels, required for fatty acid uptake into the mitochondria, were higher (+ 33%, p < 0.01) in eIMF-fed mice. The present study indicates that eIMF-fed mice have higher hepatic levels of proteins involved in fatty acid metabolism and oxidation. We speculate that eIMF feeding programs the metabolic handling of dietary lipids.

Highlights

  • We recently reported that feeding mice in their early life a diet containing a lipid structure more similar to human milk results in lower body weights and fat mass gain upon high fat feeding in later life, compared to control

  • When the physicochemical structure of human milk lipid droplets is mimicked in a rodent diet mixed with an experimental infant milk formula and fed to mice in early life, these mice gain less body weight and fat mass when challenged with a Western style diet later in life compared to a rodent diet mixed with control IMF12–14

  • At PN42, after a 4 h fast, plasma lipids were similar between groups, though adipokines leptin and adiponectin were lower in experimental infant milk formula (eIMF)-fed mice (Fig. 1E)

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Summary

Introduction

We recently reported that feeding mice in their early life a diet containing a lipid structure more similar to human milk (eIMF, Nuturis) results in lower body weights and fat mass gain upon high fat feeding in later life, compared to control (cIMF). The present study indicates that eIMF-fed mice have higher hepatic levels of proteins involved in fatty acid metabolism and oxidation. When the physicochemical structure of human milk lipid droplets is mimicked in a rodent diet mixed with an experimental infant milk formula (eIMF) and fed to mice in early life, these mice gain less body weight and fat mass when challenged with a Western style diet later in life compared to a rodent diet mixed with control IMF (cIMF)[12,13,14]. The eIMF is a concept infant milk formula with large, phospholipid coated lipid droplets (mode diameter 3–5 μm; Nuturis)[2]

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