Publications by authors named "Alastair K H MacGibbon"

11 Publications

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Qualitative and Quantitative Study of Glycosphingolipids in Human Milk and Bovine Milk Using High Performance Liquid Chromatography-Data-Dependent Acquisition-Mass Spectrometry.

Molecules 2020 Sep 3;25(17). Epub 2020 Sep 3.

School of Fundamental Sciences, Massey University, Private Bag 11222, Palmerston North 4442, New Zealand.

Cerebrosides (Crb; including glucosylceramide and galactosylceramide) and lactosylceramide (LacCer) are structurally complex lipids found in many eukaryotic cell membranes, where they play important roles in cell growth, apoptosis, cell recognition and signaling. They are also found in mammalian milk as part of the milk fat globule membrane (MFGM), making milk an important dietary component for the rapidly growing infant. This study reports the development of a robust analytical method for the identification and characterization of 44 Crb and 23 LacCer molecular species in milk, using high performance liquid chromatography-tandem mass spectrometry in data-dependent acquisition mode. For the first time, it also compares the distributions of these species in human and bovine milks, a commercial MFGM-enriched dairy ingredient (MFGM Lipid 100) and commercial standards purified from bovine milk. A method for quantifying Crb and LacCer in milk using mass spectrometry in neutral loss scan mode was developed and validated for human milk, bovine milk and MFGM Lipid 100. Human milk was found to contain approximately 9.9-17.4 µg Crb/mL and 1.3-3.0 µg LacCer/mL, whereas bovine milk (pooled milk from a Friesian herd) contained 9.8-12.0 and 14.3-16.2 µg/mL of these lipids, respectively. The process used to produce MFGM Lipid 100 was shown to have enriched these components to 448 and 1036 µg/g, respectively. No significant changes in the concentrations of both Crb and LacCer were observed during lactation.
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http://dx.doi.org/10.3390/molecules25174024DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7504816PMC
September 2020

In Vitro and In Vivo Anti-inflammatory Activity of Bovine Milkfat Globule (MFGM)-derived Complex Lipid Fractions.

Nutrients 2020 Jul 15;12(7). Epub 2020 Jul 15.

Fonterra Research & Development Centre, Palmerston North 4442, New Zealand.

Numerous health related properties have been reported for bovine milk fat globule membrane (MFGM) and its components. Here we present novel data on the in vitro and in vivo anti-inflammatory activity of various MFGM preparations which confirm and extend the concept of MFGM as a dietary anti-inflammatory agent. Cell-based assays were used to test the ability of MFGM preparations to modulate levels of the inflammatory mediators IL-1β, nitric oxide, superoxide anion, cyclo-oxygenase-2, and neutrophil elastase. In rat models of arthritis, using MFGM fractions as dietary interventions, the phospholipid-enriched MFGM isolates were effective in reducing adjuvant-induced paw swelling while there was a tendency for the ganglioside-enriched isolate to reduce carrageenan-induced rat paw oedema. These results indicate that the anti-inflammatory activity of MFGM, rather than residing in a single component, is contributed to by an array of components acting in concert against various inflammatory targets. This confirms the potential of MFGM as a nutritional intervention for the mitigation of chronic and acute inflammatory conditions.
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http://dx.doi.org/10.3390/nu12072089DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7400859PMC
July 2020

Human Milk Oligosaccharide, Phospholipid, and Ganglioside Concentrations in Breast Milk from United Arab Emirates Mothers: Results from the MISC Cohort.

Nutrients 2019 Oct 8;11(10). Epub 2019 Oct 8.

Fonterra Research and Development Centre, Dairy Farm Road, Private Bag 11029, Palmerston North 4442, New Zealand.

Human milk oligosaccharides (HMOs), phospholipids (PLs), and gangliosides (GAs) are components of human breast milk that play important roles in the development of the rapidly growing infant. The differences in these components in human milk from the United Arab Emirates (UAE) were studied in a cross-sectional trial. High-performance liquid chromatography‒mass spectrometry was used to determine HMO, PL, and GA concentrations in transitional (5-15 days) and mature (at 6 months post-partum) breast milk of mothers of the United Arab Emirates (UAE). The results showed that the average HMO (12 species), PL (7 species), and GA (2 species) concentrations quantified in the UAE mothers' transitional milk samples were (in mg/L) 8204 ± 2389, 269 ± 89, and 21.18 ± 11.46, respectively, while in mature milk, the respective concentrations were (in mg/L) 3905 ± 1466, 220 ± 85, and 20.18 ± 9.75. The individual HMO concentrations measured in this study were all significantly higher in transitional milk than in mature milk, except for 3 fucosyllactose, which was higher in mature milk. In this study, secretor and non-secretor phenotype mothers showed no significant difference in the total HMO concentration. For the PL and GA components, changes in the individual PL and GA species distribution was observed between transitional milk and mature milk. However, the changes were within the ranges found in human milk from other regions.
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http://dx.doi.org/10.3390/nu11102400DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6835464PMC
October 2019

Bovine dairy complex lipids improve in vitro measures of small intestinal epithelial barrier integrity.

PLoS One 2018 5;13(1):e0190839. Epub 2018 Jan 5.

Food Nutrition & Health Team, Food & Bio-based Products Group, AgResearch Grasslands, Palmerston North, New Zealand.

Appropriate intestinal barrier maturation is essential for absorbing nutrients and preventing pathogens and toxins from entering the body. Compared to breast-fed infants, formula-fed infants are more susceptible to barrier dysfunction-associated illnesses. In infant formula dairy lipids are usually replaced with plant lipids. We hypothesised that dairy complex lipids improve in vitro intestinal epithelial barrier integrity. We tested milkfat high in conjugated linoleic acid, beta serum (SureStart™Lipid100), beta serum concentrate (BSC) and a ganglioside-rich fraction (G600). Using Caco-2 cells as a model of the human small intestinal epithelium, we analysed the effects of the ingredients on trans-epithelial electrical resistance (TEER), mannitol flux, and tight junction protein co-localisation. BSC induced a dose-dependent improvement in TEER across unchallenged cell layers, maintained the co-localisation of tight junction proteins in TNFα-challenged cells with increased permeability, and mitigated the TEER-reducing effects of lipopolysaccharide (LPS). G600 also increased TEER across healthy and LPS-challenged cells, but it did not alter the co-location of tight junction proteins in TNFα-challenged cells. SureStart™Lipid100 had similar TEER-increasing effects to BSC when added at twice the concentration (similar lipid concentration). Ultimately, this research aims to contribute to the development of infant formulas supplemented with dairy complex lipids that support infant intestinal barrier maturation.
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http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0190839PLOS
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5755888PMC
February 2018

Dietary supplementation with bovine-derived milk fat globule membrane lipids promotes neuromuscular development in growing rats.

Nutr Metab (Lond) 2017 23;14. Epub 2017 Jan 23.

Liggins Institute, The University of Auckland, Private Bag 92019, Auckland, 1142 New Zealand.

Background: The milk fat globule membrane (MFGM) is primarily composed of polar phospho- and sphingolipids, which have established biological effects on neuroplasticity. The present study aimed to investigate the effect of dietary MFGM supplementation on the neuromuscular system during post-natal development.

Methods: Growing rats received dietary supplementation with bovine-derived MFGM mixtures consisting of complex milk lipids (CML), beta serum concentrate (BSC) or a complex milk lipid concentrate (CMLc) (which lacks MFGM proteins) from post-natal day 10 to day 70.

Results: Supplementation with MFGM mixtures enriched in polar lipids (BSC and CMLc, but not CML) increased the plasma phosphatidylcholine (PC) concentration, with no effect on plasma phosphatidylinositol (PI), phosphatidylethanolamine (PE), phosphatidylserine (PS) or sphingomyelin (SM). In contrast, muscle PC was reduced in rats receiving supplementation with both BSC and CMLc, whereas muscle PI, PE, PS and SM remained unchanged. Rats receiving BSC and CMLc (but not CML) displayed a slow-to-fast muscle fibre type profile shift (MyHCI → MyHCIIa) that was associated with elevated expression of genes involved in myogenic differentiation (myogenic regulatory factors) and relatively fast fibre type specialisation ( and ). Expression of neuromuscular development genes, including nerve cell markers, components of the synaptogenic agrin-LRP4 pathway and acetylcholine receptor subunits, was also increased in muscle of rats supplemented with BSC and CMLc (but not CML).

Conclusions: These findings demonstrate that dietary supplementation with bovine-derived MFGM mixtures enriched in polar lipids can promote neuromuscular development during post-natal growth in rats, leading to shifts in adult muscle phenotype.
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http://dx.doi.org/10.1186/s12986-017-0161-yDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5259894PMC
January 2017

Ganglioside Composition in Beef, Chicken, Pork, and Fish Determined Using Liquid Chromatography-High-Resolution Mass Spectrometry.

J Agric Food Chem 2016 Aug 4;64(32):6295-305. Epub 2016 Aug 4.

Fonterra Research and Development Centre , Dairy Farm Road, Private Bag 11029, Palmerston North 4442, New Zealand.

Gangliosides (GA) are found in animal tissues and fluids, such as blood and milk. These sialo-glycosphingolipids have bioactivities in neural development, the gastrointestinal tract, and the immune system. In this study, a high-performance liquid chromatography-mass spectrometry (HPLC-MS) method was validated to characterize and quantitate the GA in beef, chicken, pork, and fish species (turbot, snapper, king salmon, and island mackerel). For the first time, we report the concentration of GM3, the dominant GA in these foods, as ranging from 0.35 to 1.1 mg/100 g and 0.70 to 5.86 mg/100 g of meat and fish, respectively. The minor GAs measured were GD3, GD1a, GD1b, and GT1b. Molecular species distribution revealed that the GA contained long- to very-long-chain acyl fatty acids attached to the ceramide moiety. Fish GA contained only N-acetylneuraminic acid (NeuAc) sialic acid, while beef, chicken, and pork contained GD1a/b species that incorporated both NeuAc and N-glycolylneuraminic acid (NeuGc) and hydroxylated fatty acids.
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http://dx.doi.org/10.1021/acs.jafc.6b02200DOI Listing
August 2016

Lactational changes in concentration and distribution of ganglioside molecular species in human breast milk from Chinese mothers.

Lipids 2015 Nov 24;50(11):1145-54. Epub 2015 Sep 24.

Fonterra Research and Development Centre, Dairy Farm Road, Private Bag 11029, Palmerston North, 4442, New Zealand.

Gangliosides play a critical role in human brain development and function. Human breast milk (HBM) is an important dietary source of gangliosides for the growing infant. In this study, ganglioside concentrations were measured in the breast milk from a cross-sectional sample of Chinese mothers over an 8-month lactation period. The average total ganglioside concentration increased from 13.1 mg/l during the first month to 20.9 mg/l by 8 months of lactation. The average concentration during the typically solely breast-feeding period of 1‒6 months was 18.9 mg/l. This is the first study to report the relative distribution of the individual ganglioside molecular species through lactation for any population group. The ganglioside molecular species are made up of different fatty acid moieties that influence the physical properties of these gangliosides, and hence affect their function. The GM(3) molecular species containing long-chain acyl fatty acids had the most prominent changes, increasing in both concentration and relative distribution. The equivalent long-chain acyl fatty acid GD(3) molecular species typically decreased in concentration and relative distribution. The lactational trends for both concentration and relative distribution for the very long-chain acyl fatty acid molecular species were more varied. The major GM(3) and GD(3) molecular species during lactation were d40:1 and d42:1, respectively. An understanding of ganglioside molecular species distribution in HBM is essential for accurate application of mass spectrometry methods for ganglioside quantification.
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http://dx.doi.org/10.1007/s11745-015-4073-1DOI Listing
November 2015

Phenotypic population screen identifies a new mutation in bovine DGAT1 responsible for unsaturated milk fat.

Sci Rep 2015 Feb 26;5:8484. Epub 2015 Feb 26.

1] ViaLactia Biosciences (NZ) Ltd., Auckland, New Zealand [2] School of Biological Sciences, University of Auckland, Auckland, New Zealand.

Selective breeding has strongly reduced the genetic diversity in livestock species, and contemporary breeding practices exclude potentially beneficial rare genetic variation from the future gene pool. Here we test whether important traits arising by new mutations can be identified and rescued in highly selected populations. We screened milks from 2.5 million cows to identify an exceptional individual which produced milk with reduced saturated fat content, and improved unsaturated and omega-3 fatty acid concentrations. The milk traits were transmitted dominantly to her offspring, and genetic mapping and genome sequencing revealed a new mutation in a previously unknown splice enhancer of the DGAT1 gene. Homozygous carriers show features of human diarrheal disorders, and may be useful for the development of therapeutic strategies. Our study demonstrates that high-throughput phenotypic screening can uncover rich genetic diversity even in inbred populations, and introduces a novel strategy to develop novel milks with improved nutritional properties.
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http://dx.doi.org/10.1038/srep08484DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4341421PMC
February 2015

Estimation of genetic and crossbreeding parameters of fatty acid concentrations in milk fat predicted by mid-infrared spectroscopy in New Zealand dairy cattle.

J Dairy Res 2014 Aug;81(3):340-9

School of Biological Sciences,University of Auckland,Auckland,New Zealand.

The objective of this study was to estimate heritability and crossbreeding parameters (breed and heterosis effects) of various fatty acid (FA) concentrations in milk fat of New Zealand dairy cattle. For this purpose, calibration equations to predict concentration of each of the most common FAs were derived with partial least squares (PLS) using mid-infrared (MIR) spectral data from milk samples (n=850) collected in the 2003-04 season from 348 second-parity crossbred cows during peak, mid and late lactation. The milk samples produced both, MIR spectral data and concentration of the most common FAs determined using gas chromatography (GC). The concordance correlation coefficients (CCC) between the concentration of a FA determined by GC and the PLS equation ranged from 0.63 to 0.94, suggesting that some prediction equations can be considered to have substantial predictive ability. The PLS calibration equations were then used to predict the concentration of each of the fatty acids in 26,769 milk samples from 7385 cows that were herd-tested during the 2007-08 season. Data were analysed using a single-trait repeatability animal model. Shorter chain FA (16:0 and below) were significantly higher (P<0.05) in Jersey cows, while longer chain, including unsaturated longer chain FA were higher in Holstein-Friesian cows. The estimates of heritabilities ranged from 0.17 to 0.41 suggesting that selective breeding could be used to ensure milk fat composition stays aligned to consumer, market and manufacturing needs.
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http://dx.doi.org/10.1017/S0022029914000272DOI Listing
August 2014

Dairy milk fat augments paclitaxel therapy to suppress tumour metastasis in mice, and protects against the side-effects of chemotherapy.

Clin Exp Metastasis 2011 Oct 8;28(7):675-88. Epub 2011 Jul 8.

Lactopharma Consortium, University of Auckland, New Zealand.

Milk fat is a natural product containing essential nutrients as well as fatty acids and other food factors with reported anti-cancer potential. Here bovine milk fat was tested for its ability to inhibit the growth of breast and colon cancers and their metastasis to the lung and liver; either alone or in combination with the chemotherapeutic agent paclitaxel. A diet containing 5% typical anhydrous milk fat (representing ~70% of the total dietary fat component) fed to Balb/c mice delayed the appearance of subcutaneous 4T1 breast and CT26 colon cancer tumours and inhibited their metastasis to the lung and liver, when compared to the control diet containing soybean oil as the only fat component. It augmented the inhibitory effects of paclitaxel on tumour growth and metastasis, and reduced the microvessel density of tumours. It displayed no apparent organ toxicity, but instead was beneficial for well-being of tumour-bearing mice by maintaining gastrocnemius muscle and epididymal adipose tissue that were otherwise depleted by cachexia. The milk fat diet ameliorated gut damage caused by paclitaxel in non-tumour-bearing mice, as evidenced by retention of jejunal morphology, villi length and intestinal γ-glutamyl transpeptidase activity, and inhibition of crypt apoptosis. It prevented loss of red and white blood cells due to both cancer-mediated immunosuppression and the cytotoxic effects of chemotherapy. The present study warrants the use of milk fat as an adjuvant to inhibit tumour metastasis during cancer chemotherapy, and to spare patients from the debilitating side-effects of cytotoxic drugs.
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http://dx.doi.org/10.1007/s10585-011-9400-1DOI Listing
October 2011

The products from lipase-catalysed hydrolysis of bovine milkfat kill Helicobacter pylori in vitro.

FEMS Immunol Med Microbiol 2007 Mar;49(2):235-42

Department of Chemistry, The University of Auckland, Auckland, New Zealand.

Free fatty acids and monoglycerides released from milkfat by partial pregastric lipase-catalysed hydrolysis are bactericidal towards Helicobacter pylori. Two milkfat preparations were investigated: a normal bovine milkfat, and a fractionated milkfat preparation, termed ModFat, enriched in triglycerides containing short- and medium-chain fatty acids. The released products were tested for bactericidal potency against H. pylori. The potencies of the respective preparations were consistent with expected potencies calculated from individual free fatty acid and monoglyceride concentrations and their lauric acid equivalence factors (Ki). ModFat products were more bactericidal, in accordance with release of free fatty acid types of high potency, and addition of the surfactant Tween 80 to the hydrolysed lipid increased potency eight times more than did addition of lecithin. Tween 80 micelles have smaller aggregation numbers, and the mixed micelles of Tween 80/free fatty acids would be more likely to expose the bacteria to higher apparent free fatty acid concentrations.
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http://dx.doi.org/10.1111/j.1574-695X.2006.00185.xDOI Listing
March 2007