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      Beyond ingredients: Supramolecular structure of lipid droplets in infant formula affects metabolic and brain function in mouse models

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          Abstract

          Human milk beneficially affects infant growth and brain development. The supramolecular structure of lipid globules in human milk i.e., large lipid globules covered by the milk fat globule membrane, is believed to contribute to this effect, in addition to the supply of functional ingredients. Three preclinical (mouse) experiments were performed to study the effects of infant formula mimicking the supramolecular structure of human milk lipid globules on brain and metabolic health outcomes. From postnatal day 16 to 42, mouse offspring were exposed to a diet containing infant formula with large, phospholipid-coated lipid droplets (structure, STR) or infant formula with the same ingredients but lacking the unique structural properties as observed in human milk (ingredient, ING). Subsequently, in Study 1, the fatty acid composition in liver and brain membranes was measured, and expression of hippocampal molecular markers were analyzed. In Study 2 and 3 adult (Western-style diet-induced) body fat accumulation and cognitive function were evaluated. Animals exposed to STR compared to ING showed improved omega-3 fatty acid accumulation in liver and brain, and higher expression of brain myelin-associated glycoprotein. Early exposure to STR reduced fat mass accumulation in adulthood; the effect was more pronounced in animals exposed to a Western-style diet. Additionally, mice exposed to STR demonstrated better memory performance later in life. In conclusion, early life exposure to infant formula containing large, phospholipid-coated lipid droplets, that are closer to the supramolecular structure of lipid globules in human milk, positively affects adult brain and metabolic health outcomes in pre-clinical animal models.

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          Human milk composition: nutrients and bioactive factors.

          This article provides an overview of the composition of human milk, its variation, and its clinical relevance. The composition of human milk is the biological norm for infant nutrition. Human milk also contains many hundreds to thousands of distinct bioactive molecules that protect against infection and inflammation and contribute to immune maturation, organ development, and healthy microbial colonization. Some of these molecules (eg, lactoferrin) are being investigated as novel therapeutic agents. Human milk changes in composition from colostrum to late lactation, within feeds, by gestational age, diurnally, and between mothers. Feeding infants with expressed human milk is increasing. Copyright © 2013 Elsevier Inc. All rights reserved.
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            AIN-93 purified diets for laboratory rodents: final report of the American Institute of Nutrition ad hoc writing committee on the reformulation of the AIN-76A rodent diet.

            For sixteen years, the American Institute of Nutrition Rodent Diets, AIN-76 and AIN-76A, have been used extensively around the world. Because of numerous nutritional and technical problems encountered with the diet during this period, it was revised. Two new formulations were derived: AIN-93G for growth, pregnancy and lactation, and AIN-93M for adult maintenance. Some major differences in the new formulation of AIN-93G compared with AIN-76A are as follows: 7 g soybean oil/100 g diet was substituted for 5 g corn oil/100 g diet to increase the amount of linolenic acid; cornstarch was substituted for sucrose; the amount of phosphorus was reduced to help eliminate the problem of kidney calcification in female rats; L-cystine was substituted for DL-methionine as the amino acid supplement for casein, known to be deficient in the sulfur amino acids; manganese concentration was lowered to one-fifth the amount in the old diet; the amounts of vitamin E, vitamin K and vitamin B-12 were increased; and molybdenum, silicon, fluoride, nickel, boron, lithium and vanadium were added to the mineral mix. For the AIN-93M maintenance diet, the amount of fat was lowered to 40 g/kg diet from 70 g/kg diet, and the amount of casein to 140 g/kg from 200 g/kg in the AIN-93G diet. Because of a better balance of essential nutrients, the AIN-93 diets may prove to be a better choice than AIN-76A for long-term as well as short-term studies with laboratory rodents.
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              Breastfeeding and maternal health outcomes: a systematic review and meta-analysis

              Aim To evaluate the effect of breastfeeding on long-term (breast carcinoma, ovarian carcinoma, osteoporosis and type 2 diabetes mellitus) and short-term (lactational amenorrhoea, postpartum depression, postpartum weight change) maternal health outcomes. Methods A systematic literature search was conducted in PubMed, Cochrane Library and CABI databases. Outcome estimates of odds ratios or relative risks or standardised mean differences were pooled. In cases of heterogeneity, subgroup analysis and meta-regression were explored. Results Breastfeeding >12 months was associated with reduced risk of breast and ovarian carcinoma by 26% and 37%, respectively. No conclusive evidence of an association between breastfeeding and bone mineral density was found. Breastfeeding was associated with 32% lower risk of type 2 diabetes. Exclusive breastfeeding and predominant breastfeeding were associated with longer duration of amenorrhoea. Shorter duration of breastfeeding was associated with higher risk of postpartum depression. Evidence suggesting an association of breastfeeding with postpartum weight change was lacking. Conclusion This review supports the hypothesis that breastfeeding is protective against breast and ovarian carcinoma, and exclusive breastfeeding and predominant breastfeeding increase the duration of lactational amenorrhoea. There is evidence that breastfeeding reduces the risk of type 2 diabetes. However, an association between breastfeeding and bone mineral density or maternal depression or postpartum weight change was not evident.
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                Author and article information

                Contributors
                Role: ConceptualizationRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draft
                Role: ConceptualizationRole: MethodologyRole: Writing – review & editing
                Role: Formal analysisRole: MethodologyRole: VisualizationRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – review & editing
                Role: ConceptualizationRole: Formal analysisRole: InvestigationRole: MethodologyRole: SupervisionRole: Writing – original draft
                Role: Editor
                Journal
                PLoS One
                PLoS One
                plos
                PLOS ONE
                Public Library of Science (San Francisco, CA USA )
                1932-6203
                2 August 2023
                2023
                : 18
                : 8
                : e0282816
                Affiliations
                [1 ] Danone Nutricia Research, Utrecht, The Netherlands
                [2 ] Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, Netherlands
                International School, Vietnam National University, VIET NAM
                Author notes

                Competing Interests: I have read the journal’s policy and the authors of this manuscript have the following competing interests: This study was funded by Danone Nutricia Research. The funder provided support to the current study by covering research costs and in the form of salaries for authors AO, LH, SR and LS. The funder discloses a granted patent application using data that is also described in the submitted work (EP EP2753191A1 USE OF INFANT FORMULA WITH LARGE LIPID GLOBULES). GvD has collaborated with the funder on part of the submitted work for which his institution is compensated financially. The research is done in relation to development of a product by Danone, which is not yet released in (worldwide) markets. This does not alter our adherence to PLOS ONE policies on sharing data and materials.

                Author information
                https://orcid.org/0000-0003-0722-7948
                Article
                PONE-D-23-05243
                10.1371/journal.pone.0282816
                10395839
                37531323
                8dd1e52f-d408-4b44-932b-4084bbee58c4
                © 2023 Oosting et al

                This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

                History
                : 22 February 2023
                : 28 June 2023
                Page count
                Figures: 6, Tables: 3, Pages: 18
                Funding
                Funded by: funder-id http://dx.doi.org/10.13039/100015766, Danone Nutricia Research;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100015766, Danone Nutricia Research;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100015766, Danone Nutricia Research;
                Award Recipient :
                Funded by: funder-id http://dx.doi.org/10.13039/100015766, Danone Nutricia Research;
                Award Recipient :
                This study was funded by Danone Nutricia Research. The funder provided support to the current study by covering research costs and in the form of salaries for authors AO, LH, SR and LS. As these authors are employed by the funder, the funder had a role in the study design, data collection and analysis, decision to publish and preparation of the manuscript.
                Categories
                Research Article
                Biology and Life Sciences
                Nutrition
                Diet
                Medicine and Health Sciences
                Nutrition
                Diet
                Biology and Life Sciences
                Biochemistry
                Lipids
                Lipid Structure
                Biology and Life Sciences
                Biochemistry
                Lipids
                Biology and Life Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Adipose Tissue
                Medicine and Health Sciences
                Anatomy
                Biological Tissue
                Connective Tissue
                Adipose Tissue
                Biology and Life Sciences
                Biochemistry
                Lipids
                Fatty Acids
                Biology and Life Sciences
                Nutrition
                Diet
                Beverages
                Milk
                Medicine and Health Sciences
                Nutrition
                Diet
                Beverages
                Milk
                Biology and Life Sciences
                Anatomy
                Body Fluids
                Milk
                Medicine and Health Sciences
                Anatomy
                Body Fluids
                Milk
                Biology and Life Sciences
                Physiology
                Body Fluids
                Milk
                Biology and Life Sciences
                Biochemistry
                Lipids
                Phospholipids
                Biology and Life Sciences
                Biochemistry
                Lipids
                Lipid Metabolism
                Biology and Life Sciences
                Biochemistry
                Metabolism
                Lipid Metabolism
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