Melnik, Bodo C. and Weiskirchen, Ralf and John, Swen Malte and Stremmel, Wolfgang and Leitzmann, Claus and Weiskirchen, Sabine and Schmitz, Gerd (2025) White Adipocyte Stem Cell Expansion Through Infant Formula Feeding: New Insights into Epigenetic Programming Explaining the Early Protein Hypothesis of Obesity. INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 26 (10): 4493. ISSN 1661-6596, 1422-0067
Full text not available from this repository. (Request a copy)Abstract
Prolonged breastfeeding (BF), as opposed to artificial infant formula feeding (FF), has been shown to prevent the development of obesity later in life. The aim of our narrative review is to investigate the missing molecular link between postnatal protein overfeeding-often referred to as the "early protein hypothesis"-and the subsequent transcriptional and epigenetic changes that accelerate the expansion of adipocyte stem cells (ASCs) in the adipose vascular niche during postnatal white adipose tissue (WAT) development. To achieve this, we conducted a search on the Web of Science, Google Scholar, and PubMed databases from 2000 to 2025 and reviewed 750 papers. Our findings revealed that the overactivation of mechanistic target of rapamycin complex 1 (mTORC1) and S6 kinase 1 (S6K1), which inhibits wingless (Wnt) signaling due to protein overfeeding, serves as the primary pathway promoting ASC commitment and increasing preadipocyte numbers. Moreover, excessive protein intake, combined with the upregulation of the fat mass and obesity-associated gene (FTO) and a deficiency of breast milk-derived microRNAs from lactation, disrupts the proper regulation of FTO and Wnt pathway components. This disruption enhances ASC expansion in WAT while inhibiting brown adipose tissue development. While BF has been shown to have protective effects against obesity, the postnatal transcriptional and epigenetic changes induced by excessive protein intake from FF may predispose infants to early and excessive ASC commitment in WAT, thereby increasing the risk of obesity later in life.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | MITOTIC CLONAL EXPANSION; ACTIVATED-RECEPTOR-GAMMA; GROWTH-FACTOR-I; P70 S6 KINASE; ADIPOSE-TISSUE DEVELOPMENT; TRANSFER-RNA SYNTHETASE; LONG-TERM CONSEQUENCES; DIET-INDUCED OBESITY; GLYCOGEN-SYNTHASE KINASE-3-BETA; RIBONUCLEIC-ACID EXPRESSION; adipocyte stem cell; adipogenesis; breastfeeding; enhancer of zeste homolog 2; epigenetic regulation; formula feeding; fat mass- and obesity-associated gene; mechanistic target of rapamycin complex 1; obesity; S6 kinase 1; wingless signaling |
| Subjects: | 600 Technology > 610 Medical sciences Medicine |
| Divisions: | Medicine > Lehrstuhl für Klinische Chemie und Laboratoriumsmedizin |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 17 Jun 2026 05:14 |
| Last Modified: | 17 Jun 2026 05:14 |
| URI: | https://pred.uni-regensburg.de/id/eprint/67490 |
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