Risk of Fat Mass- and Obesity-Associated Gene-Dependent Obesogenic Programming by Formula Feeding Compared to Breastfeeding

Nutrients, vol. 16, pp. 2451

Abstract

It is the purpose of this review to compare differences in postnatal epigenetic programming at the level of DNA and RNA methylation and later obesity risk between infants receiving artificial formula feeding (FF) in contrast to natural breastfeeding (BF). FF bears the risk of aberrant epigenetic programming at the level of DNA methylation and enhances the expression of the RNA demethylase fat mass- and obesity-associated gene (FTO), pointing to further deviations in the RNA methylome. Based on a literature search through Web of Science, Google Scholar, and PubMed databases concerning the dietary and epigenetic factors influencing FTO gene and FTO protein expression and FTO activity, FTO’s impact on postnatal adipogenic programming was investigated. Accumulated translational evidence underscores that total protein intake as well as tryptophan, kynurenine, branched-chain amino acids, milk exosomal miRNAs, NADP, and NADPH are crucial regulators modifying FTO gene expression and FTO activity. Increased FTO-mTORC1-S6K1 signaling may epigenetically suppress the WNT/β-catenin pathway, enhancing adipocyte precursor cell proliferation and adipogenesis. Formula-induced FTO-dependent alterations of the N6-methyladenosine (m6A) RNA methylome may represent novel unfavorable molecular events in the postnatal development of adipogenesis and obesity, necessitating further investigations. BF provides physiological epigenetic DNA and RNA regulation, a compelling reason to rely on BF.

Authors 5

1. Bodo Clemens Melnik corresponding

   Osnabrück University

   Affiliation as printed

   Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, D-49076 Osnabrück, Germany

2. Ralf Weiskirchen Aachen Institute of Molecular Pathobiochemistry Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC)

   RWTH Aachen University · Universitätsklinikum Aachen

   Affiliation as printed

   Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry (IFMPEGKC), RWTH University Hospital Aachen, D-52074 Aachen, Germany

3. Wolfgang Stremmel
   Affiliation as printed

   Praxis for Internal Medicine, Beethovenstrasse 2, D-76530 Baden-Baden, Germany

4. Swen Malte John

   Osnabrück University

   Affiliation as printed

   Department of Dermatology, Environmental Medicine and Health Theory, University of Osnabrück, D-49076 Osnabrück, Germany

   Institute for Interdisciplinary Dermatological Prevention and Rehabilitation (iDerm), University of Osnabrück, D-49076 Osnabrück, Germany

5. Gerd Schmitz

   University of Regensburg · University Hospital Regensburg

   Affiliation as printed

   Institute for Clinical Chemistry and Laboratory Medicine, University Hospital of Regensburg, D-93053 Regensburg, Germany