Excessive Leucine-mTORC1-Signalling of Cow Milk-Based Infant Formula: The Missing Link to Understand Early Childhood Obesity

Article, Review English OPEN
Bodo C. Melnik (2012)
  • Publisher: Hindawi Limited
  • Journal: Journal of Obesity, volume 2,012 (issn: 2090-0708, eissn: 2090-0716)
  • Related identifiers: pmc: PMC3317169, doi: 10.1155/2012/197653
  • Subject: Review Article | Internal medicine | RC31-1245 | Article Subject

Increased protein supply by feeding cow-milk-based infant formula in comparison to lower protein content of human milk is a well-recognized major risk factor of childhood obesity. However, there is yet no conclusive biochemical concept explaining the mechanisms of formula-induced childhood obesity. It is the intention of this article to provide the biochemical link between leucine-mediated signalling of mammalian milk proteins and adipogenesis as well as early adipogenic programming. Leucine has been identified as the predominant signal transducer of mammalian milk, which stimulates the nutrient-sensitive kinase mammalian target of rapamycin complex 1 (mTORC1). Leucine thus functions as a maternal-neonatal relay for mTORC1-dependent neonatal β-cell proliferation and insulin secretion. The mTORC1 target S6K1 plays a pivotal role in stimulation of mesenchymal stem cells to differentiate into adipocytes and to induce insulin resistance. It is of most critical concern that infant formulas provide higher amounts of leucine in comparison to human milk. Exaggerated leucine-mediated mTORC1-S6K1 signalling induced by infant formulas may thus explain increased adipogenesis and generation of lifelong elevated adipocyte numbers. Attenuation of mTORC1 signalling of infant formula by leucine restriction to physiologic lower levels of human milk offers a great chance for the prevention of childhood obesity and obesity-related metabolic diseases.
  • References (140)
    140 references, page 1 of 14

    Troiano, R. P., Flegal, K. M.. Overweight children and adolescents: description, epidemiology, and demographics. Pediatrics. 1998; 101 (3, supplement 2): 497-504

    Zhao, J., Grant, S. F. A.. Genetics of Childhood Obesity. Journal of Obesity. 2011; 2011-9

    Yaturu, S.. Obesity and type 2 diabetes. Journal of Diabetes Mellitus. 2011; 1 (4): 79-95

    Thorn, J., Waller, M., Johansson, M., Marild, S.. Overweight among four-year-old children in relation to early growth characteristics and socioeconomic factors. Journal of Obesity. 2010; 2010-6

    Armitage, J. A., Taylor, P. D., Poston, L.. Experimental models of developmental programming: consequences of exposure to an energy rich diet during development. The Journal of Physiology. 2005; 565 (1): 3-8

    Kramer, M. S.. Do breast-feeding and delayed introduction of solid foods protect against subsequent obesity?. The Journal of Pediatrics. 1981; 98 (6): 883-887

    Von Kries, R., Koletzko, B., Sauerwald, T., Von Mutius, E., Barnert, D., Grunert, V., Von Voss, H.. Breast feeding and obesity: cross sectional study. British Medical Journal. 1999; 318 (7203): 147-150

    Ziegler, E. E.. Growth of breast-fed and formula-fed infants. Nestlé Nutrition Institute Workshop Series Pediatric Program. 2006 (58): 51-59

    Koletzko, B., Von Kries, R., Closa, R., Escribano, J., Scaglioni, S., Giovannini, M., Beyer, J., Demmelmair, H., Gruszfeld, D., Dobrzanska, A., Sengier, A., Langhendries, J. P., Cachera, M. F. R., Grote, V.. Lower protein in infant formula is associated with lower weight up to age 2 y: a randomized clinical trial. The American Journal of Clinical Nutrition. 2009; 89 (6): 1836-1845

    Koletzko, B., Von Kries, R., Closa, R., Escribano, J.. Can infant feeding choices modulate later obesity risk?. The American Journal of Clinical Nutrition. 2009; 89 (5): 1502S-1508S

  • Related Research Results (2)
  • Similar Research Results (2)
  • Metrics
    No metrics available
Share - Bookmark