The potential mechanistic link between allergy and obesity development and infant formula feeding

DC FieldValueLanguage
dc.contributor.authorMelnik, Bodo C.
dc.date.accessioned2021-12-23T16:02:56Z-
dc.date.available2021-12-23T16:02:56Z-
dc.date.issued2014
dc.identifier.issn17101484
dc.identifier.urihttps://osnascholar.ub.uni-osnabrueck.de/handle/unios/5707-
dc.description.abstractThis article provides a new view of the cellular mechanisms that have been proposed to explain the links between infant formula feeding and the development of atopy and obesity. Epidemiological evidence points to an allergy- and obesity-preventive effect of breastfeeding. Both allergy and obesity development have been traced back to accelerated growth early in life. The nutrient-sensitive kinase mTORC1 is the master regulator of cell growth, which is predominantly activated by amino acids. In contrast to breastfeeding, artificial infant formula feeding bears the risk of uncontrolled excessive protein intake overactivating the infant's mTORC1 signalling pathways. Overactivated mTORC1 enhances S6K1-mediated adipocyte differentiation, but negatively regulates growth and differentiation of FoxP3(+) regulatory T-cells (Tregs), which are deficient in atopic individuals. Thus, the ``early protein hypothesis'' not only explains increased mTORC1-mediated infant growth but also the development of mTORC1-driven diseases such as allergy and obesity due to a postnatal deviation from the appropriate axis of mTORC1-driven metabolic and immunologic programming. Remarkably, intake of fresh unpasteurized cow's milk exhibits an allergy-preventive effect in farm children associated with increased FoxP3(+) Treg numbers. In contrast to unprocessed cow's milk, formula lacks bioactive immune-regulatory microRNAs, such as microRNA-155, which plays a major role in FoxP3 expression. Uncontrolled excessive protein supply by formula feeding associated with the absence of bioactive microRNAs and bifidobacteria in formula apparently in a synergistic way result in insufficient Treg maturation. Treg deficiency allows Th2-cell differentiation promoting the development of allergic diseases. Formula-induced mTORC1 overactivation is thus the critical mechanism that explains accelerated postnatal growth, allergy and obesity development on one aberrant pathway.
dc.language.isoen
dc.publisherBIOMED CENTRAL LTD
dc.relation.ispartofALLERGY ASTHMA AND CLINICAL IMMUNOLOGY
dc.subjectAllergy
dc.subjectBreastfeeding
dc.subjectCHILDHOOD ASTHMA
dc.subjectFARM MILK CONSUMPTION
dc.subjectFoxP3
dc.subjectGROWTH-FACTOR-I
dc.subjectHUMAN BREAST-MILK
dc.subjectIMMUNE-RELATED MICRORNAS
dc.subjectImmunology
dc.subjectInfant formula
dc.subjectMAMMALIAN TARGET
dc.subjectmTORC1
dc.subjectObesity
dc.subjectPANCREATIC BETA-CELLS
dc.subjectPOLYUNSATURATED FATTY-ACIDS
dc.subjectPostnatal growth acceleration
dc.subjectRegulatory T-cell
dc.subjectREGULATORY T-CELLS
dc.subjectSIGNALING PATHWAY
dc.titleThe potential mechanistic link between allergy and obesity development and infant formula feeding
dc.typereview
dc.identifier.doi10.1186/1710-1492-10-37
dc.identifier.isiISI:000339513800001
dc.description.volume10
dc.identifier.eissn17101492
dc.publisher.place236 GRAYS INN RD, FLOOR 6, LONDON WC1X 8HL, ENGLAND
dcterms.isPartOf.abbreviationAllerg Asthma Clin. Immunol.
dcterms.oaStatusgold, Green Published
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