Early life nutrition possibly influences long-term metabolic outcomes. Previous studies in mice showed that adult obesity and energy metabolism can be improved by early life exposure to an infant milk formula (IMF) with large (3-5μm), (milk)-phospholipid coated lipid droplets (Concept diet, Nuturis®). This study examined the effects of the Concept diet on (adult) fasting insulin sensitivity and hepatic mitochondrial capacity. From postnatal day (PN) 16 to PN42, male C57BL/6j mice were exposed to a semisynthetic rodent diet containing Concept or Control (CTRL)-IMF. Subsequently, mice were fed either Western-style (WSD) or standard rodent diet (AIN) from PN42 to PN98 and sacrificed after 3 hours fasting, at PN98. Homeostasis model assessment insulin resistance index (HOMA-IR) was calculated from fasting insulin and glucose levels. Mitochondrial function was assessed by high-resolution respirometry in liver tissue at PN98 using substrates stimulating β-oxidation (β-OX) and tricarboxylic acid cycle (TCA) flux. Plasma thiobarbituric acid reactive substances (TBARS), a marker of lipid peroxidation, were measured fluorometrically. At PN98, WSD induced insulin resistance in CTRL, but not in Concept fed mice (p<0.05). Furthermore, Concept mice on WSD had a lower liver weight (p<0.05) and 69% higher maximal β-OX compared to CTRL (p<0.05). Liver fat content increased with WSD independent of initial diet (p<0.05) and was not different between CTRL and Concept groups. Yet, plasma TBARS were 23% lower in Concept compared to CTRL mice fed WSD (p<0.05).

In conclusion, early life feeding of the Concept diet improved hepatic oxidative capacity and protected adult mice against diet-induced insulin resistance. These results suggest that early postnatal metabolic priming may decrease systemic oxidative damage which can help to maintain liver health in an obesogenic environment.


T. Jelenik: Employee; Self; Boehringer Ingelheim Pharmaceuticals, Inc. A. Kodde: Employee; Self; Danone Nutricia Research. D. Pesta: None. E. Rohbeck: None. B. Dewidar: None. E. Phielix: None. A. Oosting: Employee; Self; Danone Nutricia Research. E.M. van der Beek: Employee; Self; Danone Nutricia Research. M. Roden: Advisory Panel; Self; Servier. Board Member; Self; Poxel SA. Consultant; Self; Eli Lilly and Company, Gilead Sciences, Inc., ProSciento, TARGET PharmaSolutions. Research Support; Self; Boehringer Ingelheim International GmbH, Novartis Pharma K.K., Sanofi US. Speaker’s Bureau; Self; Novo Nordisk A/S.


Danone Nutricia Research

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.