Dietary lipid droplet structure in postnatal life improves hepatic energy and lipid metabolism in a mouse model for postnatal programming

Kodde, Andrea; Pesta, Dominik; Phielix, Esther; Oosting, Annemarie; Rohbeck, Elisabeth; Dewidar, Bedair; Mastrototaro, Lucia; Trenkamp, Sandra; Keijer, Jaap; Beek, Eline M. van der; Roden, Michael

doi:10.1016/j.phrs.2022.106193

Cited by 4 publications

(4 citation statements)

References 72 publications

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“…Indeed, the relative protein expression of OXHPOS subunits, in particular mitochondrial cytochrome c oxidase I subunit (Complex IV) were altered by Nuturis diet in retroperitoneal WAT depots in a previous study with similar study design. [33] Further, Nuturis feeding increased the functional mitochondrial marker maximum respiratory capacity in liver tissues at PN42 (direct effect) and PN98 (as a programmed effect), [50] supporting the gene effects seen on OXPHOS complexes in WAT here. Further functional experiments are needed however to establish the role of early-life nutrition on the mitochondrial electron transport chain function in adulthood.…”

Section: Discussionsupporting

confidence: 66%

Early‐Life Exposure to Dietary Large Phospholipid‐Coated Lipid Droplets Improves Markers of Metabolic and Immune Function in Adipose Tissue Later in Life in a Mouse Model

Klein Hazebroek,

Baars,

Mischke

et al. 2023

Molecular Nutrition Food Res

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ScopeHuman milk (HM) is considered optimal nutrition for infants, beneficially programming adult health outcomes including reduced obesity risk. Early life exposure to infant formula with lipid droplets closely resembling the structural properties of HM lipid globules (Nuturis) attenuated white adipose tissue (WAT) accumulation in mice upon adult western‐style diet (WSD) feeding. Here, the study aims to elucidate underlying mechanisms.Methods and resultsMice are raised on control or Nuturis diets between postnatal days 16–42 followed by either standard diet or WSD for 16 weeks. While the adult body composition of mice on a standard diet is not significantly affected, Nuturis reduced adiposity in mice on WSD. Morphologically, mean adipocyte size is reduced in Nuturis‐raised mice, independent of adult diet exposure, and WAT macrophage content is reduced, albeit not significantly. Transcriptomics of epididymal WAT indicate potential beneficial effects on energy metabolism and macrophage function by Nuturis.ConclusionReduced adult adiposity by early life exposure to Nuturis appears to be associated with smaller adipocytes and alterations in WAT immune and energy metabolism. These results suggest that early modulation of WAT structure and/or function may contribute to the protective programming effects of the early‐life Nuturis diet on later‐life adiposity.

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Section: Discussionsupporting

confidence: 66%

Early‐Life Exposure to Dietary Large Phospholipid‐Coated Lipid Droplets Improves Markers of Metabolic and Immune Function in Adipose Tissue Later in Life in a Mouse Model

Klein Hazebroek,

Baars,

Mischke

et al. 2023

Molecular Nutrition Food Res

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“…In previous studies, using similar programming models, we have comprehensively shown that early life exposure to concept IFs containing large, MFGM coated lipid droplets resulted in beneficial effects on later life body composition (41, 44, 47, 48), metabolic health (49–54) and brain outcomes (43, 46, 55, 56), when compared to IFs with small lipid droplets and no MFGM added. However, due to the experimental design of these studies, the effects of the mere presence of MFGM versus effects of the complex supramolecular lipid droplet structure with large lipid droplets and MFGM fragments at the interface could not be distinguished.…”

Section: Discussionmentioning

confidence: 94%

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

Oosting

Harvey

Ringler

et al. 2023

Preprint

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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, 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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“…In previous studies, using similar nutritional programming models, we have comprehensively shown that early life exposure to concept IFs containing large, MFGM coated lipid droplets resulted in beneficial effects on later life body composition [ 41 , 44 , 47 , 48 ], metabolic health [ 49 – 54 ] and brain outcomes [ 43 , 46 , 55 , 56 ], when compared to IFs with small lipid droplets and no MFGM added. However, due to the experimental design of these studies, the effects of the mere presence of MFGM versus effects of the complex supramolecular lipid droplet structure with large lipid droplets and MFGM fragments at the interface could not be distinguished.…”

Section: Discussionmentioning

confidence: 99%

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

et al. 2023

Self Cite

View full text Add to dashboard Cite

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.

show abstract

Dietary lipid droplet structure in postnatal life improves hepatic energy and lipid metabolism in a mouse model for postnatal programming

Cited by 4 publications

References 72 publications

Early‐Life Exposure to Dietary Large Phospholipid‐Coated Lipid Droplets Improves Markers of Metabolic and Immune Function in Adipose Tissue Later in Life in a Mouse Model

Early‐Life Exposure to Dietary Large Phospholipid‐Coated Lipid Droplets Improves Markers of Metabolic and Immune Function in Adipose Tissue Later in Life in a Mouse Model

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

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

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