Nutritional programming in early life: the role of dietary lipid quality for future health

Worldwide, overweight and obesity have increased dramatically, not only in high income countries. Clearly, unhealthy diets and sedentary lifestyle are important drivers of the increased obesity rates, but increasing evidence indicates that the vulnerability for later life non-communicable diseases is set during the first 1000 days, the period from conception until 2 years of age. The growth during this period is faster than during any other period in life. Dietary fats provide energy for growth, but also supply essential fatty acid (FA) precursors for long chain polyunsaturated FA that are building blocks and signals for adipose tissue development. Both epidemiological and experimental data support the notion that specific improvements in dietary fat quality, e.g. specific changes in the fatty acid composition as well as the structural organization of dietary lipids, may reduce the risk of obesity and other adverse outcomes in later life, but clinical evidence is limited and largely inconclusive. We anticipate that effects of such relatively small improvements in nutrient quality may be difficult to measure on the short term and have limited impact in healthy children. However, for children that already experience challenging conditions in the womb and have a higher risk profile based on deviations in birthweight and postnatal growth, the potential protective effects of improved dietary lipid quality in early life could be more substantial. Results from randomized clinical studies testing improved lipid quality concepts will help to develop specific strategies to adapt infant nutrition based on the need with the aim to improve long term outcomes.

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Effects of an early life diet containing large phospholipid-coated lipid globules on hepatic lipid metabolism in mice

Scientific Reports ◽

10.1038/s41598-020-72777-y ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Onne A. H. O. Ronda ◽

Bert J. M. van de Heijning ◽

Ingrid Martini ◽

Albert Gerding ◽

Justina C. Wolters ◽

...

Keyword(s):

Fatty Acid ◽

Early Life ◽

Acid Metabolism ◽

Acyl Chain ◽

Later Life ◽

Fatty Acyl ◽

Dietary Lipids ◽

Bile Acid Metabolism ◽

Fatty Acyl Chain ◽

Acid Uptake

Abstract We recently reported that feeding mice in their early life a diet containing a lipid structure more similar to human milk (eIMF, Nuturis) results in lower body weights and fat mass gain upon high fat feeding in later life, compared to control (cIMF). To understand the underlying mechanisms, we now explored parameters possibly involved in this long-term effect. Male C57BL/6JOlaHsd mice, fed rodent diets containing eIMF or cIMF from postnatal (PN) day 16–42, were sacrificed at PN42. Hepatic proteins were measured using targeted proteomics. Lipids were assessed by LC–MS/MS (acylcarnitines) and GC-FID (fatty-acyl chain profiles). Early life growth and body composition, cytokines, and parameters of bile acid metabolism were similar between the groups. Hepatic concentrations of multiple proteins involved in β-oxidation (+ 17%) the TCA cycle (+ 15%) and mitochondrial antioxidative proteins (+ 28%) were significantly higher in eIMF versus cIMF-fed mice (p < 0.05). Hepatic l-carnitine levels, required for fatty acid uptake into the mitochondria, were higher (+ 33%, p < 0.01) in eIMF-fed mice. The present study indicates that eIMF-fed mice have higher hepatic levels of proteins involved in fatty acid metabolism and oxidation. We speculate that eIMF feeding programs the metabolic handling of dietary lipids.

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An early-life diet containing large phospholipid-coated lipid globules programmes later-life postabsorptive lipid trafficking in high-fat diet- but not in low-fat diet-fed mice

British Journal Of Nutrition ◽

10.1017/s0007114520002421 ◽

2020 ◽

pp. 1-11 ◽

Cited By ~ 1

Author(s):

Onne A. H. O. Ronda ◽

Bert J. M. van de Heijning ◽

Ingrid A. Martini ◽

Martijn Koehorst ◽

Rick Havinga ◽

...

Keyword(s):

High Fat Diet ◽

Early Life ◽

Later Life ◽

Mass Gain ◽

Dietary Lipids ◽

Lipid Absorption ◽

Milk Formula ◽

Intragastric Administration ◽

High Fat ◽

Lipid Trafficking

Abstract Feeding mice in early life a diet containing an experimental infant milk formula (Nuturis®; eIMF), with a lipid structure similar to human milk, transiently lowered body weight (BW) and fat mass gain upon Western-style diet later in life, when compared with mice fed diets based on control IMF (cIMF). We tested the hypothesis that early-life eIMF feeding alters the absorption or the postabsorptive trafficking of dietary lipids in later life. Male C57BL/6JOlaHsd mice were fed eIMF/cIMF from postnatal day 16–42, followed by low- (LFD, American Institute of Nutrition (AIN)-93 G, 7 wt% fat) or high-fat diet (HFD, D12451, 24 wt% fat) until day 63–70. Lipid absorption rate and tissue concentrations were determined after intragastric administration of stable isotope (2H or 13C) labelled lipids in separate groups. Lipid enrichments in plasma and tissues were analysed using GC-MS. The rate of triolein absorption was similar between eIMF and cIMF fed LFD: 3·2 (sd 1·8) and 3·9 (sd 2·1) and HFD: 2·6 (sd 1·7) and 3·8 (sd 3·0) % dose/ml per h. Postabsorptive lipid trafficking, that is, concentrations of absorbed lipids in tissues, was similar in the eIMF and cIMF groups after LFD. Tissue levels of absorbed TAG after HFD feeding were lower in heart (–42 %) and liver (–46 %), and higher in muscle (+81 %, all P < 0·05) in eIMF-fed mice. In conclusion, early-life IMF diet affected postabsorptive trafficking of absorbed lipids after HFD, but not LFD. Changes in postabsorptive lipid trafficking could underlie the observed lower BW and body fat accumulation in later life upon a persistent long-term obesogenic challenge.

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Early Life Nutrition

Science Progress ◽

10.3184/003685018x15360040523721 ◽

2018 ◽

Vol 101 (4) ◽

pp. 332-359 ◽

Cited By ~ 2

Author(s):

Susan Finn ◽

Eamonn P. Culligan ◽

William J. Snelling ◽

Roy D. Sleator

Keyword(s):

Health Outcomes ◽

Early Life ◽

Infant Nutrition ◽

Functional Performance ◽

Later Life ◽

Sole Source ◽

Protective Effects ◽

Optimal Health ◽

Feeding Methods ◽

The Impact

Nutritionally, the first 1,000 days of an infant's life – from conception to two years – has been identified as a highly influential period, during which lasting health can be achieved. Significant evidence links patterns of infant feeding to both short and long-term health outcomes, many of which can be prevented through nutritional modifications. Recommended globally, breastfeeding is recognised as the gold standard of infant nutrition; providing key nutrients to achieve optimal health, growth and development, and conferring immunologic protective effects against disease. Nevertheless, infant formulas are often the sole source of nutrition for many infants during the first stage of life. Producers of infant formula strive to supply high quality, healthy, safe alternatives to breast milk with a comparable balance of nutrients to human milk imitating its composition and functional performance measures. The concept of ‘nutritional programming’, and the theory that exposure to specific conditions, can predispose an individual's health status in later life has become an accepted dictum, and has sparked important nutritional research prospects. This review explores the impact of early life nutrition, specifically, how different feeding methods affect health outcomes.

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Dietary lipid structure in early life does not program fat absorption in later life

The FASEB Journal ◽

10.1096/fasebj.2018.32.1_supplement.925.6 ◽

2018 ◽

Vol 32 (S1) ◽

Author(s):

Onne Ronda ◽

Rick Havinga ◽

Bert Heijning ◽

Folkert Kuipers ◽

Henkjan Verkade

Keyword(s):

Early Life ◽

Later Life ◽

Dietary Lipid ◽

Fat Absorption ◽

Lipid Structure

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Models and mechanisms of energy balance regulation in the young

Proceedings of The Nutrition Society ◽

10.1017/s0029665108008628 ◽

2008 ◽

Vol 67 (4) ◽

pp. 327-333 ◽

Cited By ~ 1

Author(s):

Julian G. Mercer

Keyword(s):

Body Weight ◽

Energy Balance ◽

Early Life ◽

Single Gene ◽

Later Life ◽

Overweight And Obesity ◽

Regulatory Systems ◽

Definition Of ◽

The Uk ◽

The Impact

The proportion of the child and adolescent population that is in appropriate energy balance is declining throughout the developed world, and childhood obesity is a particular problem in the UK relative to other northern European countries. Assessment of the underlying causes of obesity, and the different routes to its development, may assist in the definition of successful intervention strategies. The network of peripheral and central (brain) regulatory systems that underlie energy balance and body weight and composition can, for the most part, only be approached experimentally through the study of appropriate laboratory animal models. This problem is particularly acute when the target is overweight and obesity in the young. Some of the mechanisms underlying the development of energy imbalance and specifically the onset of overweight and obesity in the young, and the metabolic health consequences of obesity, can be addressed by examination of experimental rodent models in which mutation of a single gene causes early-onset extreme obesity, genetic susceptibility to obesity is revealed in an obesogenic environment or early-life nutritional experience programmes susceptibility to obesity or metabolic problems in later life. These studies highlight genes that are essential to normal body-weight regulation in rodents and man, the impact of diet and diet-induced obesity on regulatory systems in the young and the potential sensitivity of developing regulatory systems to nutritional experiences in utero and during early life.

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Rat liver mitochondrial membrane characteristics and mitochondrial functions are more profoundly altered by dietary lipid quantity than by dietary lipid quality: effect of different nutritional lipid patterns

British Journal Of Nutrition ◽

10.1017/s000711451100331x ◽

2011 ◽

Vol 107 (5) ◽

pp. 647-659 ◽

Cited By ~ 44

Author(s):

Manar Aoun ◽

Christine Feillet-Coudray ◽

Gilles Fouret ◽

Béatrice Chabi ◽

David Crouzier ◽

...

Keyword(s):

Fish Oil ◽

Rat Liver ◽

Mitochondrial Membrane ◽

Dietary Lipid ◽

Dietary Lipids ◽

Complex Iii ◽

Lipid Quality ◽

Mitochondrial Functions ◽

Fish Oil Diet ◽

Lard Diet

Dietary lipids are known to affect the composition of the biological membrane and functions that are involved in cell death and survival. The mitochondrial respiratory chain enzymes are membrane protein complexes whose function depends on the composition and fluidity of the mitochondrial membrane lipid. The present study aimed at investigating the impact of different nutritional patterns of dietary lipids on liver mitochondrial functions. A total of forty-eight Wistar male rats were divided into six groups and fed for 12 weeks with a basal diet, lard diet or fish oil diet, containing either 50 or 300 g lipid/kg. The 30 % lipid intake increased liver NEFA, TAG and cholesterol levels, increased mitochondrial NEFA and TAG, and decreased phospholipid (PL) levels. SFA, PUFA and unsaturation index (UI) increased, whereas MUFA andtrans-fatty acids (FA) decreased in the mitochondrial membrane PL in 30 % fat diet-fed rats compared with 5 % lipid diet-fed rats. PL UI increased with fish oil dietv.basal and lard-rich diets, and PLtrans-FA increased with lard dietv.basal and fish oil diets. The 30 % lipid diet intake increased mitochondrial membrane potential, membrane fluidity, mitochondrial respiration and complex V activity, and decreased complex III and IV activities. With regard to lipid quality effects, β-oxidation decreased with the intake of basal or fish oil diets compared with that of the lard diet. The intake of a fish oil diet decreased complex III and IV activities compared with both the basal and lard diets. In conclusion, the characteristics and mitochondrial functions of the rat liver mitochondrial membrane are more profoundly altered by the quantity of dietary lipid than by its quality, which may have profound impacts on the pathogenesis and development of non-alcoholic fatty liver disease.

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The Effects of Early Life Stress, Postnatal Diet Modulation, and Long-Term Western-Style Diet on Later-Life Metabolic and Cognitive Outcomes

Nutrients ◽

10.3390/nu12020570 ◽

2020 ◽

Vol 12 (2) ◽

pp. 570 ◽

Cited By ~ 2

Author(s):

Maralinde R. Abbink ◽

Lidewij Schipper ◽

Eva F.G. Naninck ◽

Cato M.H. de Vos ◽

Romy Meier ◽

...

Keyword(s):

Cognitive Function ◽

Life Stress ◽

Early Life ◽

Early Life Stress ◽

Later Life ◽

Dietary Lipids ◽

Cognitive Outcomes ◽

Milk Formula ◽

Structural Level ◽

Early Life Exposure

Early life stress (ES) increases the risk to develop metabolic and brain disorders in adulthood. Breastfeeding (exclusivity and duration) is associated with improved metabolic and neurocognitive health outcomes, and the physical properties of the dietary lipids may contribute to this. Here, we tested whether early life exposure to dietary lipids mimicking some physical characteristics of breastmilk (i.e., large, phospholipid-coated lipid droplets; Concept Nuturis® infant milk formula (N-IMF)), could protect against ES-induced metabolic and brain abnormalities under standard circumstances, and in response to prolonged Western-style diet (WSD) in adulthood. ES was induced by exposing mice to limited nesting material from postnatal day (P) 2 to P9. From P16 to P42, male offspring were fed a standard IMF (S-IMF) or N-IMF, followed by either standard rodent diet (SD) or WSD until P230. We then assessed body composition development, fat mass, metabolic hormones, hippocampus-dependent cognitive function, and neurogenesis (proliferation and survival). Prolonged WSD resulted in an obesogenic phenotype at P230, which was not modulated by previous ES or N-IMF exposure. Nevertheless, ES and N-IMF modulated the effect of WSD on neurogenesis at P230, without affecting cognitive function, highlighting programming effects of the early life environment on the hippocampal response to later life challenges at a structural level.

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The effect of dietary lipid changes on the fatty acid composition and function of liver, heart and brain mitochondria in the rat at different ages

British Journal Of Nutrition ◽

10.1079/bjn19940126 ◽

1994 ◽

Vol 71 (2) ◽

pp. 193-202 ◽

Cited By ~ 41

Author(s):

V. Barzanti ◽

M. Battino ◽

A. Baracca ◽

M. Cavazzoni ◽

M. Cocchi ◽

...

Keyword(s):

Fatty Acid Composition ◽

Fatty Acid ◽

Acid Composition ◽

Structural Integrity ◽

Brain Mitochondria ◽

Dietary Lipid ◽

Dietary Lipids ◽

And Function ◽

Fatty Acid Compositions

A correlation between dietary lipids and cellular enzyme activities is a problem that has only been partially addressed by nutritionists. Therefore, changes in the fatty acid composition and the activities of some key metabolic enzymes (ubiquinol-2-cytochrome c reductase (EC 1.10.2.2), cytochrome oxidase (EC 1.9.3.1) and ATPase (EC 3.6.1.3)) in the mitochondria of liver, heart and brain of rats fed on diets differing extensively in their polyunsaturated fatty acid compositions have been investigated. The results showed that fatty acid compositional changes brought about by the dietary differences were associated with extensive changes in the activities of these key enzymes in the mitochondria. The extent of the influence differed considerably with the period over which the diets were fed. The role of dietary lipids to effect changes through the preservation of membrane structural integrity is discussed.

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Effect of the lipase inhibitor orlistat and of dietary lipid on the absorption of radiolabelled triolein, tri-γ-linolenin and tripalmitin in mice

British Journal Of Nutrition ◽

10.1079/bjn19950090 ◽

1995 ◽

Vol 73 (6) ◽

pp. 851-862 ◽

Cited By ~ 16

Author(s):

Dorothea Isler ◽

Charistine Moeglen ◽

Nigel Gains ◽

Marcel K. Meier

Keyword(s):

Fatty Acid ◽

Dietary Lipid ◽

Selective Inhibitor ◽

Dietary Lipids ◽

Lipase Inhibitor ◽

Novel Approach ◽

Triacylglycerol Hydrolysis

Orlistat, a selective inhibitor of gastrointestinal lipases, was used to investigate triacylglycerol absorption. Using mice and a variety of emulsified dietary lipids we found that the absorption of radiolabelled tripalmitin (containing the fatty acid 16:0), but not of triolein (18: 1n−9) or tri-γ-linolenin (18:3n−6), was incomplete from meals rich in esterified palmitate. Further, the absorption of radiolabelled tri-γ-linolenin, from both saturated and unsaturated dietary triacylglycerols, was 1·3- to 2-fold more potently inhibited by orlistat than that of triolein and tripalmitin. These radiolabelled triacylglycerols, which have the same fatty acid in all three positions, may not always be accurate markers of the absorption of dietary triacylglycerols. Orlistat was more effective at inhibiting the absorption of radiolabelled triacylglycerols with which it was codissolved than those added separately, which indicates that equilibration between lipid phases in the stomach may not always be complete. The saturation of the dietary lipid had little or no effect on the potency of orlistat. Orlistat provides a novel approach for studying the role of triacylglycerol hydrolysis in the overall process of triacylglycerol absorption.

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Early Origins of Body Mass in Later Life: Examining Childhood Risks and Adult Pathways

Journal of Health and Social Behavior ◽

10.1177/00221465211005419 ◽

2021 ◽

pp. 002214652110054

Author(s):

Sarah A. Mustillo ◽

Miao Li ◽

Patricia Morton ◽

Kenneth F. Ferraro

Keyword(s):

Physical Activity ◽

Body Mass ◽

Health Risks ◽

Early Life ◽

Life Experiences ◽

Later Life ◽

Childhood Experiences ◽

Older Adulthood ◽

Early Life Exposure ◽

Nationally Representative

Prior research reveals that negative early-life experiences play a major role in the development of obesity in later life, but few studies identify mechanisms that alter the lifetime risk of obesity. This study examines the influence of negative childhood experiences on body mass index (BMI) and obesity (BMI ≥30) during older adulthood and the psychosocial and behavioral pathways involved. Using a nationally representative sample, we examine the influence of cumulative misfortune as well as five separate domains of misfortune on BMI and obesity. Results show that four of the five domains are associated with BMI and obesity either directly, indirectly, or both. The influence of cumulative misfortune on the outcomes is mediated by three adult factors: socioeconomic status, depressive symptoms, and physical activity. The mediators identified here provide targets for intervention among older adults to help offset the health risks of excess BMI attributable of early-life exposure to misfortune.

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