Register      Login

VOLUME 3 , ISSUE 1 ( January-March, 2024 ) > List of Articles


Milk Fat Globules: 2024 Updates

Akhil Maheshwari, Harshvardhan Mantry, Nitasha Bagga, Adrianna Frydrysiak-Brzozowska, Jargalsaikhan Badarch, Md Mozibur Rahman

Keywords : 1,4-β-N-acetylmuraminidase, Absorbable sphingosine, Acetyl-CoA carboxylase 1, Acyl-CoA synthetase, Acyl-CoA synthetase long chain family member 3, Acyl-CoA synthetase long chain family member 5, Adipophilin, Adipose differentiation-related proteins, ADPF, Alpha-1-antitrypsin, Annexin, Apocrine-like glands, Apolipoprotein A1, Apolipoprotein A-IV, Apolipoprotein C-III, Apolipoprotein E, Apolipoproteins, Arachidonic acid, Arginine-glycine-aspartate (RGD), Bacteroidetes, Bayley Scales of Infant and Toddler Development II, Bifidobacterium, Bile salt-stimulated lipase, Bone marrow stromal antigen 2, C16-ceramide, C18:0, C24-ceramide, Casein micelles, Cathelicidins, C-C motif chemokine ligand 2, CD9 antigen, Ceramidase, Ceramide, Ceramide-1-phosphate, Cerebrosides, Chlorella vulgaris, Cholesterol, Choline, Chordin-like protein 2, Clusterin, Complement C3, Conjugated linoleic acid, Coriobacteriaceae, De Brouckère mean diameter, Dermcidin, Desulfovibrionaceae, Diacylglycerol acyltransferase 1, Disialylated gangliosi

Citation Information : Maheshwari A, Mantry H, Bagga N, Frydrysiak-Brzozowska A, Badarch J, Rahman MM. Milk Fat Globules: 2024 Updates. 2024; 3 (1):19-37.

DOI: 10.5005/jp-journals-11002-0085

License: CC BY-NC 4.0

Published Online: 26-03-2024

Copyright Statement:  Copyright © 2024; The Author(s).


Milk fat globules (MFGs) are a remarkable example of nature's ingenuity. Human milk (HM) carries contains 3–5% fat, 0.8–0.9% protein, 6.9–7.2% carbohydrate calculated as lactose, and 0.2% mineral constituents. Most of these nutrients are carried in these MFGs, which are composed of an energy-rich triacylglycerol (TAG) core surrounded by a triple membrane structure. The membrane contains polar lipids, specialized proteins, glycoproteins, and cholesterol. Each of these bioactive components serves important nutritional, immunological, neurological, and digestive functions. These MFGs are designed to release energy rapidly in the upper gastrointestinal tract and then persist for some time in the gut lumen so that the protective bioactive molecules are conveyed to the colon. These properties may shape the microbial colonization and innate immune properties of the developing gastrointestinal tract. Milk fat globules in milk from humans and ruminants may resemble in structure but there are considerable differences in size, profile, composition, and specific constituents. There are possibilities to not only enhance the nutritional composition in a goal-oriented fashion to correct specific deficiencies in the infant but also to use these fat globules as a nutraceutical in infants who require specific treatments. To mention a few, there might be possibilities in enhancing neurodevelopment, in defense against gastrointestinal and respiratory tract infections, improving insulin sensitivity, treating chronic inflammation, and altering plasma lipids. This review provides an overview of the composition, structure, and biological activities of the various components of the MFGs. We have assimilated research findings from our own laboratory with an extensive review of the literature utilizing key terms in multiple databases including PubMed, EMBASE, and Science Direct. To avoid bias in the identification of studies, keywords were short-listed a priori from anecdotal experience and PubMed's Medical Subject Heading (MeSH) thesaurus.

PDF Share
  1. Ballard O, Morrow AL. Human milk composition: Nutrients and bioactive factors. Pediatr Clin North Am 2013;60(1):49–74. DOI: 10.1016/j.pcl.2012.10.002.
  2. Samuel TM, Zhou Q, Giuffrida F, et al. Nutritional and non-nutritional composition of human milk is modulated by maternal, infant, and methodological factors. Front Nutr 2020;7:576133. DOI: 10.3389/fnut.2020.576133.
  3. Maheshwari A. Fats in human milk: 2022 updates on chemical composition. Newborn (Clarksville) 2022;1(4):384–396. DOI: 10.5005/jp-journals-11002-0050.
  4. Valverde R, Dinerstein NA, Vain N. Mother's own milk and donor milk. World Rev Nutr Diet 2021;122:212–224. DOI: 10.1159/000514733.
  5. Butte NF. Fat intake of children in relation to energy requirements. Am J Clin Nutr 2000;72(5 Suppl):1246S–1252S. DOI: 10.1093/ajcn/72.5.1246s.
  6. Young BE, Krebs NF. Complementary feeding: Critical considerations to optimize growth, nutrition, and feeding behavior. Curr Pediatr Rep 2013;1(4):247–256. DOI: 10.1007/s40124-013-0030-8.
  7. WHO U, USAID A, AED U. Indicators for assessing infant and young child feeding practices. Geneva: World Health Organization. 2008.
  8. Argov N, Lemay DG, German JB. Milk fat globule structure & function; nanosciece comes to milk production. Trends Food Sci Technol 2008;19(12):10. DOI: 10.1016/j.tifs.2008.07.006.
  9. Argov N, Wachsmann-Hogiu S, Freeman SL, et al. Size-dependent lipid content in human milk fat globules. J Agric Food Chem 2008;56(16):7446–7450. DOI: 10.1021/jf801026a.
  10. Cavaletto M, Givonetti A, Cattaneo C. The immunological role of milk fat globule membrane. Nutrients 2022;14(21):4574. DOI: 10.3390/nu14214574.
  11. Chai C, Oh S, Imm JY. Roles of milk fat globule membrane on fat digestion and infant nutrition. Food Sci Anim Resour 2022;42(3): 351–371. DOI: 10.5851/kosfa.2022.e11.
  12. Huang QX, Yang J, Hu M, et al. Milk fat globule membrane proteins are involved in controlling the size of milk fat globules during conjugated linoleic acid-induced milk fat depression. J Dairy Sci 2022;105(11):9179–9190. DOI: 10.3168/jds.2022-22131.
  13. Li T, Gao J, Du M, et al. Milk fat globule membrane attenuates high-fat diet-induced obesity by inhibiting adipogenesis and increasing uncoupling protein 1 expression in white adipose tissue of mice. Nutrients 2018;10(3):331. DOI: 10.3390/nu10030331.
  14. Lopez C. Milk fat globules enveloped by their biological membrane: Unique colloidal assemblies with a specific composition and structure. Curr Opin Colloid Interface Sci 2011;16(5)391–404. DOI: 10.1016/j.cocis.2011.05.007.
  15. Sun Y, Roos YH, Miao S. Changes in milk fat globules and membrane proteins prepared from pH-adjusted bovine raw milk. Foods 2022;11(24):4107. DOI: 10.3390/foods11244107.
  16. Thum C, Roy NC, Everett DW, et al. Variation in milk fat globule size and composition: A source of bioactives for human health. Crit Rev Food Sci Nutr 2023;63(1):87–113. DOI: 10.1080/10408398.2021.1944049.
  17. Thum C, Wall C, Day L, et al. Changes in human milk fat globule composition throughout lactation: A review. Front Nutr 2022; 9:835856. DOI: 10.3389/fnut.2022.835856.
  18. Walter L, Narayana VK, Fry R, et al. Milk fat globule size development in the mammary epithelial cell: A potential role for ether phosphatidylethanolamine. Sci Rep 2020;10(1):12299. DOI: 10.1038/s41598-020-69036-5.
  19. McManaman JL. Lipid transport in the lactating mammary gland. J Mammary Gland Biol Neoplasia 2014;19(1):35–42. DOI: 10.1007/s10911-014-9318-8.
  20. Lee H, Padhi E, Hasegawa Y, et al. Compositional dynamics of the milk fat globule and its role in infant development. Front Pediatr 2018;6:313. DOI: 10.3389/fped.2018.00313.
  21. Newburg DS, Peterson JA, Ruiz-Palacios GM, et al. Role of human-milk lactadherin in protection against symptomatic rotavirus infection. Lancet 1998;351(9110):1160–1164. DOI: 10.1016/s0140-6736(97)10322-1.
  22. Hahn-Holbrook J, Fish A, Glynn LM. Human milk omega-3 fatty acid composition is associated with infant temperament. Nutrients 2019;11(12):2964. DOI: 10.3390/nu11122964.
  23. Ding D, He X, Agarry IE, et al. Profile of human milk phospholipids at different lactation stages with UPLC/Q-TOF-MS: Characterization, distribution, and differences. J Agric Food Chem 2023;71(16):6326–6337. DOI: 10.1021/acs.jafc.2c07512.
  24. Seki D, Errerd T, Hall LJ. The role of human milk fats in shaping neonatal development and the early life gut microbiota. Microbiome Res Rep 2023;2(2):8. DOI: 10.20517/mrr.2023.09.
  25. Boquien CY. Human milk: An ideal food for nutrition of preterm newborn. Front Pediatr 2018;6:295. DOI: 10.3389/fped.2018.00295.
  26. Mead MN. Contaminants in human milk: Weighing the risks against the benefits of breastfeeding. Environ Health Perspect 2008;116(10):A427–A434. PMID: 18941560.
  27. Jukkola A, Partanen R, Rojas OJ, et al. Separation of milk fat globules via microfiltration: Effect of diafiltration media and opportunities for stream valorization. J Dairy Sci 2016;99(11):8644–8654. DOI: 10.3168/jds.2016-11422.
  28. Wiking L, Gregersen SB, Hansen SF, et al. Heat-induced changes in milk fat and milk fat globules and its derived effects on acid dairy gelation–A review. Int Dairy J 2022;127:105213. DOI: 10.1016/j.idairyj.2021.105213.
  29. Raza GS, Herzig KH, Leppaluoto J. Invited review: Milk fat globule membrane-A possible panacea for neurodevelopment, infections, cardiometabolic diseases, and frailty. J Dairy Sci 2021;104(7): 7345–7363. DOI: 10.3168/jds.2020-19649.
  30. Steffen F, Hansen BP, Rasmussen JT, et al. Placing pasteurisation before or after microfiltration impacts the protein composition of milk fat globule membrane material. Int Dairy J 2018;81:35–41. DOI: 10.1016/j.idairyj.2017.12.015.
  31. Alshehab M, Reis MG, Day L, et al. Milk fat globules, a novel carrier for delivery of exogenous cholecalciferol. Food Res Int 2019;126:108579. DOI: 10.1016/j.foodres.2019.108579.
  32. Acevedo-Fani A, Dave A, Singh H. Nature-assembled structures for delivery of bioactive compounds and their potential in functional foods. Front Chem 2020;8:564021. DOI: 10.3389/fchem.2020.564021.
  33. Rahman MM, Khatun S, Kabir N, et al. Establishment of the first religiously-compliant human milk bank in bangladesh. Newborn (Clarksville) 2022;1(4):376–383. DOI: 10.5005/jp-journals-11002-0047.
  34. Raz C, Paramonov MM, Shemesh M, et al. The milk fat globule size governs a physiological switch for biofilm formation by Bacillus subtilis. Front Nutr 2022;9:844587. DOI: 10.3389/fnut.2022.844587.
  35. Masedunskas A, Chen Y, Stussman R, et al. Kinetics of milk lipid droplet transport, growth, and secretion revealed by intravital imaging: Lipid droplet release is intermittently stimulated by oxytocin. Mol Biol Cell 2017;28(7):935–946. DOI: 10.1091/mbc.E16-11-0776.
  36. Di Marzo L, Cree P, Barbano DM. Prediction of fat globule particle size in homogenized milk using Fourier transform mid-infrared spectra. J Dairy Sci 2016;99(11):8549–8560. DOI: 10.3168/jds.2016-11284.
  37. Kowalczuk PB, Drzymala J. Physical meaning of the Sauter mean diameter of spherical particulate matter. Particulate Science and Technology 2016;34(6):645–647. DOI: 10.1080/02726351.2015. 1099582.
  38. Lyu F, Thomas M, Hendriks WH, et al. Size reduction in feed technology and methods for determining, expressing and predicting particle size: A review. Animal Feed Science and Technology 2020;261:114347. DOI:
  39. Pinto G, Baptista A, Silva F, et al. Study on the influence of the ball material on abrasive particles’ dynamics in ball-cratering thin coatings wear tests. Materials (Basel) 2021;14(3):668. DOI: 10.3390/ma14030668.
  40. Michalski MC, Briard V, Michel F, et al. Size distribution of fat globules in human colostrum, breast milk, and infant formula. J Dairy Sci 2005;88(6):1927–1940. DOI: 10.3168/jds.S0022-0302(05)72868-X.
  41. Wei W, Li D, Jiang C, et al. Phospholipid composition and fat globule structure II: Comparison of mammalian milk from five different species. Food Chem 2022;388:132939. DOI: 10.1016/j.foodchem.2022.132939.
  42. Anto L, Warykas SW, Torres-Gonzalez M, et al. Milk polar lipids: Underappreciated lipids with emerging health benefits. Nutrients 2020;12(4):1001. DOI: 10.3390/nu12041001.
  43. Aumeistere L, Ciprovica I, Zavadska D, et al. Impact of maternal diet on human milk composition among lactating women in latvia. Medicina (Kaunas) 2019;55(5):173. DOI: 10.3390/medicina55050173.
  44. Verardo V, Gomez-Caravaca AM, Arraez-Roman D, et al. Recent advances in phospholipids from colostrum, milk and dairy by-products. Int J Mol Sci 2017;18(1):173. DOI: 10.3390/ijms18010173.
  45. Tan S, Chen C, Zhao A, et al. The dynamic changes of gangliosides in breast milk and the intake of gangliosides in maternal and infant diet in three cities of China. Int J Clin Exp Pathol 2020;13(11):2870–2888. PMID: 33284868.
  46. Kolter T. Ganglioside biochemistry. ISRN Biochem 2012;2012:506160. DOI: 10.5402/2012/506160.
  47. Mansson HL. Fatty acids in bovine milk fat. Food Nutr Res 2008;52(1). DOI: 10.3402/fnr.v52i0.1821.
  48. Contarini G, Povolo M. Phospholipids in milk fat: Composition, biological and technological significance, and analytical strategies. Int J Mol Sci 2013;14(2):2808–2831. DOI: 10.3390/ijms14022808.
  49. He X, McClorry S, Hernell O, et al. Digestion of human milk fat in healthy infants. Nutr Res 2020;83:15–29. DOI: 10.1016/j.nutres.2020.08.002.
  50. Linn JG. Factors affecting the composition of milk from dairy cows. In: Products NRCUCoTOtItNAoA (Eds). Designing Foods: Animal Product Options in the Marketplace. Washington (DC): National Academies Press (US); 1988.
  51. Sanchez-Hernandez S, Esteban-Munoz A, Gimenez-Martinez R, et al. A comparison of changes in the fatty acid profile of human milk of spanish lactating women during the first month of lactation using gas chromatography-mass spectrometry. A comparison with infant formulas. Nutrients 2019;11(12):3055. DOI: 10.3390/nu11123055.
  52. Yang F, Chen G. The nutritional functions of dietary sphingomyelin and its applications in food. Front Nutr 2022;9:1002574. DOI: 10.3389/fnut.2022.1002574.
  53. Sinanoglou VJ, Cavouras D, Boutsikou T, et al. Factors affecting human colostrum fatty acid profile: A case study. PLoS One 2017;12(4):e0175817. DOI: 10.1371/journal.pone.0175817.
  54. Jia W, Zhang R, Zhu Z, et al. A high-throughput comparative proteomics of milk fat globule membrane reveals breed and lactation stages specific variation in protein abundance and functional differences between milk of saanen dairy goat and holstein bovine. Front Nutr 2021;8:680683. DOI: 10.3389/fnut.2021.680683.
  55. Schultz-Pernice I, Engelbrecht LK, Petricca S, et al. Morphological analysis of human milk membrane enclosed structures reveals diverse cells and cell-like milk fat globules. J Mammary Gland Biol Neoplasia 2020;25(4):397–408. DOI: 10.1007/s10911-020-09472-1.
  56. Mulder H, Walstra P. The milk fat globule: Commonwealth Agricultural Bureaux Farnham Royal; 1974. pp. 54–97.
  57. Andrews AT, Anderson M, Goodenough PW. A study of the heat stabilities of a number of indigenous milk enzymes. Journal of Dairy Research 1987;54(2):237–246. DOI:
  58. Hansen SF, Larsen LB, Wiking L. Thermal effects on IgM-milk fat globule-mediated agglutination. Journal of Dairy Research 2019;86(1):108–113. DOI: 10.1017/S0022029918000778.
  59. Burge K, Vieira F, Eckert J, et al. Lipid composition, digestion, and absorption differences among neonatal feeding strategies: Potential implications for intestinal inflammation in preterm infants. Nutrients 2021;13(2):550. DOI: 10.3390/nu13020550.
  60. Rogalska E, Ransac S, Verger R. Stereoselectivity of lipases. II. Stereoselective hydrolysis of triglycerides by gastric and pancreatic lipases. J Biol Chem 1990;265(33):20271–20276. PMID: 2243091.
  61. Gimenez MS, Oliveros LB, Gomez NN. Nutritional deficiencies and phospholipid metabolism. Int J Mol Sci 2011;12(4):2408–2433. DOI: 10.3390/ijms12042408.
  62. Manoni M, Di Lorenzo C, Ottoboni M, et al. Comparative proteomics of milk fat globule membrane (MFGM) proteome across species and lactation stages and the potentials of MFGM fractions in infant formula preparation. Foods 2020;9(9):1251. DOI: 10.3390/foods9091251.
  63. Wang C, Qiao X, Gao Z, et al. Advancement on milk fat globule membrane: Separation, identification, and functional properties. Front Nutr 2021;8:807284. DOI: 10.3389/fnut.2021.807284.
  64. Hansen SF, Hogan SA, Tobin J, et al. Microfiltration of raw milk for production of high-purity milk fat globule membrane material. J Food Eng 2020;276:109887. DOI: 10.1016/j.jfoodeng.2019.109887.
  65. Hu Y, Thaler J, Nieuwland R. Extracellular vesicles in human milk. Pharmaceuticals (Basel) 2021;14(10):1050. DOI: 10.3390/ph14101050.
  66. Argov-Argaman N, Smilowitz JT, Bricarello DA, et al. Lactosomes: Structural and compositional classification of unique nanometer-sized protein lipid particles of human milk. J Agric Food Chem 2010;58(21):11234–11242. DOI: 10.1021/jf102495s.
  67. Mizuno K, Nishida Y, Taki M, et al. Is increased fat content of hindmilk due to the size or the number of milk fat globules? Int Breastfeed J 2009;4:7. DOI: 10.1186/1746-4358-4-7.
  68. Argov-Argaman N, Raz C, Roth Z. Progesterone regulation of milk fat globule size is VLDL dependent. Front Endocrinol (Lausanne) 2020;11:596. DOI: 10.3389/fendo.2020.00596.
  69. Churakov M, Karlsson J, Edvardsson Rasmussen A, et al. Milk fatty acids as indicators of negative energy balance of dairy cows in early lactation. Animal 2021;15(7):100253. DOI: 10.1016/j.animal.2021.100253.
  70. Capuco AV, Akers RM. The origin and evolution of lactation. J Biol 2009;8(4):37. DOI: 10.1186/jbiol139.
  71. Oftedal OT. The evolution of milk secretion and its ancient origins. Animal 2012;6(3):355–368. DOI: 10.1017/S1751731111001935.
  72. Oftedal OT. The mammary gland and its origin during synapsid evolution. J Mammary Gland Biol Neoplasia 2002;7(3):225–252. DOI: 10.1023/a:1022896515287.
  73. Oftedal OT. The origin of lactation as a water source for parchment-shelled eggs. J Mammary Gland Biol Neoplasia 2002;7(3):253–266. DOI: 10.1023/a:1022848632125.
  74. Folk GE Jr, Semken HA Jr. The evolution of sweat glands. Int J Biometeorol 1991;35(3):180–186. DOI: 10.1007/BF01049065.
  75. Lefevre CM, Sharp JA, Nicholas KR. Evolution of lactation: Ancient origin and extreme adaptations of the lactation system. Annu Rev Genomics Hum Genet 2010;11:219–238. DOI: 10.1146/annurev-genom-082509-141806.
  76. Kemp TS. The origin and early radiation of the therapsid mammal-like reptiles: A palaeobiological hypothesis. J Evol Biol 2006;19(4): 1231–1247. DOI: 10.1111/j.1420-9101.2005.01076.x.
  77. Pavlova T, Spacil Z, Vidova V, et al. Adipophilin and perilipin 3 positively correlate with total lipid content in human breast milk. Sci Rep 2020;10(1):360. DOI: 10.1038/s41598-019-57241-w.
  78. Chong BM, Reigan P, Mayle-Combs KD, et al. Determinants of adipophilin function in milk lipid formation and secretion. Trends Endocrinol Metab 2011;22(6):211–217. DOI: 10.1016/j.tem.2011.04.003.
  79. Haarsma L, Nelesen S, VanAndel E, et al. Simulating evolution of protein complexes through gene duplication and co-option. J Theor Biol 2016;399:22–32. DOI: 10.1016/j.jtbi.2016.03.028.
  80. Wells JN, Bergendahl LT, Marsh JA. Co-translational assembly of protein complexes. Biochem Soc Trans 2015;43(6):1221–1226. DOI: 10.1042/BST20150159.
  81. Verma HC. Concepts of physics part I. 4th edition. New Delhi, India: S. Chand & Company Ltd; 2008. pp. 284–286.
  82. Lewis M. Food dimensions; size, shape and numbers. Sawston, United Kingdom: Woodhead Publishing; 2023. pp. 12–86.
  83. Koroleva M, Tokarev A, Yurtov E. Modeling droplet aggregation and percolation clustering in emulsions. Arab J Chem 2019;12(8): 4458–4465. DOI: 10.1016/j.arabjc.2016.07.001.
  84. Leong K, Wang F. A molecular dynamics investigation of the surface tension of water nanodroplets and a new technique for local pressure determination through density correlation J Chem Phys 2018;148(14):144503. DOI: 10.1063/1.5004985.
  85. Colombo M, Wright C. First principles in the life sciences: The free-energy principle, organicism, and mechanism. Synthese 2021;198(14):3463–3488. DOI: 10.1007/s11229-018-01932-w.
  86. Panchal BR, Truong T, Prakash S, et al. Effect of fat globule size on the churnability of dairy cream. Food Res Int 2017;99(Pt 1):229–338. DOI: 10.1016/j.foodres.2017.05.027.
  87. Davies-Jones R. An expression for effective buoyancy in surroundings with horizontal density gradients. J Atmos Sci 2003;60(23):2922–2955. DOI: 10.1175/1520-0469(2003)060<2922:AEFEBI>2.0.CO;2.
  88. Bannon P. Theoretical foundations for models of moist convection. J Atmos Sci 2002;59(12):1967–1982. DOI:<1967:TFFMOM>2.0.CO;2.
  89. Das P. A non-archimedean approach to the equations of convection dynamics. J Atmos Sci 1979;36(11):2183–2190. DOI: 10.1175/1520-0469(1979)036<2183:ANAATT>2.0.CO;2.
  90. Wang L, Chen W, Guo H. Response of membrane tension to gravity in an approximate cell model. Theor Biol Med Model 2019;16(1):19. DOI: 10.1186/s12976-019-0116-2.
  91. Dey S, Zeeshan Ali S, Padhi E. Terminal fall velocity: The legacy of Stokes from the perspective of fluvial hydraulics. Proc Math Phys Eng Sci 2019;475(2228):20190277. DOI: 10.1098/rspa.2019.0277.
  92. Cartwright JHE. Stokes’ law, viscometry, and the Stokes falling sphere clock. Philos Trans A Math Phys Eng Sci 2020;378(2179):20200214. DOI: 10.1098/rsta.2020.0214.
  93. Gomez-Solano JR, July C, Mehl J, et al. Non-equilibrium work distribution for interacting colloidal particles under friction. New J Phys 2015;17:045026. DOI: 10.1088/1367-2630/17/4/045026.
  94. Smoczynski M. Role of phospholipid flux during milk secretion in the mammary gland. J Mammary Gland Biol Neoplasia 2017;22(2):117–129. DOI: 10.1007/s10911-017-9376-9.
  95. D'Incecco P, Ong L, Pellegrino L, et al. Effect of temperature on the microstructure of fat globules and the immunoglobulin-mediated interactions between fat and bacteria in natural raw milk creaming. J Dairy Sci 2018;101(4):2984–2997. DOI: 10.3168/jds.2017-13580.
  96. Wu C, Qian T, Sheng P. Droplet spreading driven by van der Waals force: a molecular dynamics study. J Phys Condens Matter 2010;22(32):325101. DOI: 10.1088/0953-8984/22/32/325101.
  97. Lahiri R, Arvind, Sain A. Brownian motion in a classical ideal gas: A microscopic approach to Langevin's equation. Pramana - J Phys 2004;62:1015–1028. DOI: 10.1007/BF02705249.
  98. Rings D, Schachoff R, Selmke M, et al. Hot brownian motion. Phys Rev Lett 2010;105(9):090604. DOI: 10.1103/PhysRevLett.105.090604.
  99. Mokshin AV, Yulmetyev RM, Hänggi P. Diffusion processes and memory effects. New J Phys 2005;7:9. DOI: 10.1088/1367-2630/7/1/009.
  100. Pitre L, Plimmer MD, Sparasci F, et al. Determinations of the Boltzmann constant. Comptes Rendus Physique 2019;20(1–2):129–139. DOI: 10.1016/j.crhy.2018.11.007.
  101. de Oliveira MJ. Boltzmann stochastic thermodynamics. Phys Rev E 2019;99(5–1):052138. DOI: 10.1103/PhysRevE.99.052138.
  102. Sinha KP, Das S, Karyappa RB, et al. Electrohydrodynamics of vesicles and capsules. Langmuir 2020;36(18):4863–4886. DOI: 10.1021/acs.langmuir.9b03971.
  103. Wei T, Huang Y, Weng C, et al. Lipid rafts may affect the coalescence of milk fat globules through phase transition after thermal treatment. Food Chem 2023;399:133867. DOI: 10.1016/j.foodchem.2022.133867.
  104. Pan J, Chen M, Li N, et al. Bioactive functions of lipids in the milk fat globule membrane: A comprehensive review. Foods 2023;12(20):3755. DOI: 10.3390/foods12203755.
  105. Lu J, Argov-Argaman N, Anggrek J, et al. The protein and lipid composition of the membrane of milk fat globules depends on their size. J Dairy Sci 2016;99(6):4726–4738. DOI: 10.3168/jds.2015-10375.
  106. Wooding FB, Mather IH. Ultrastructural and immunocytochemical evidence for the reorganisation of the milk fat globule membrane after secretion. Cell Tissue Res 2017;367(2):283–295. DOI: 10.1007/s00441-016-2505-8.
  107. Yasuda T, Al Sazzad MA, Jantti NZ, et al. The influence of hydrogen bonding on sphingomyelin/colipid interactions in bilayer membranes. Biophys J 2016;110(2):431–440. DOI: 10.1016/j.bpj.2015.11.3515.
  108. Smoczyński M, Staniewski B, Kiełczewska K. Composition and structure of the bovine milk fat globule membrane—Some nutritional and technological implications. Food Reviews International 2012;28(2):188–202. DOI: 10.1080/87559129.2011.595024.
  109. McManaman JL. Formation of milk lipids: A molecular perspective. Clin Lipidol 2009;4(3):391–401. DOI: 10.2217/clp.09.15.
  110. Spitsberg VL, Matitashvili E, Gorewit RC. Association and coexpression of fatty-acid-binding protein and glycoprotein CD36 in the bovine mammary gland. Eur J Biochem 1995;230(3):872–878. DOI: 10.1111/j.1432-1033.1995.tb20630.x.
  111. Yang Y, Spitzer E, Kenney N, et al. Members of the fatty acid binding protein family are differentiation factors for the mammary gland. J Cell Biol 1994;127(4):1097–1109. DOI: 10.1083/jcb.127.4.1097.
  112. Reinhardt TA, Lippolis JD. Developmental changes in the milk fat globule membrane proteome during the transition from colostrum to milk. J Dairy Sci 2008;91(6):2307–2318. DOI: 10.3168/jds.2007-0952.
  113. Yang MT, Lan QY, Liang X, et al. Lactational changes of phospholipids content and composition in chinese breast milk. Nutrients 2022;14(8):1539. DOI: 10.3390/nu14081539.
  114. Ma L, Fong BY, MacGibbon AKH, et al. Qualitative and quantitative study of glycosphingolipids in human milk and bovine milk using high performance liquid chromatography-data-dependent acquisition-mass spectrometry. Molecules 2020;25(17):4024. DOI: 10.3390/molecules25174024.
  115. Nilsson A, Duan RD. Absorption and lipoprotein transport of sphingomyelin. J Lipid Res 2006;47(1):154–171. DOI: 10.1194/jlr.M500357-JLR200.
  116. Nieto-Ruiz A, Garcia-Santos JA, Verdejo-Roman J, et al. Infant formula supplemented with milk fat globule membrane, long-chain polyunsaturated fatty acids, and synbiotics is associated with neurocognitive function and brain structure of healthy children aged 6 years: The COGNIS study. Front Nutr 2022;9:820224. DOI: 10.3389/fnut.2022.820224.
  117. Jiang B, Xia Y, Zhou L, et al. Safety and tolerance assessment of milk fat globule membrane-enriched infant formulas in healthy term Chinese infants: A randomised multicenter controlled trial. BMC Pediatr 2022;22(1):465. DOI: 10.1186/s12887-022-03507-8.
  118. Ambrozej D, Dumycz K, Dziechciarz P, et al. Milk fat globule membrane supplementation in children: Systematic review with meta-analysis. Nutrients 2021;13(3):714. DOI: 10.3390/nu13030714.
  119. Khor GL, Tan SS, Stoutjesdijk E, et al. Temporal changes in breast milk fatty acids contents: A case study of malay breastfeeding women. Nutrients 2020;13(1):101. DOI: 10.3390/nu13010101.
  120. Delplanque B, Gibson R, Koletzko B, et al. Lipid quality in infant nutrition: Current knowledge and future opportunities. J Pediatr Gastroenterol Nutr 2015;61(1):8–17. DOI: 10.1097/MPG.0000000000000818.
  121. Hadley KB, Ryan AS, Forsyth S, et al. The essentiality of arachidonic acid in infant development. Nutrients 2016;8(4):216. DOI: 10.3390/nu8040216.
  122. Li J, Pora BLR, Dong K, et al. Health benefits of docosahexaenoic acid and its bioavailability: A review. Food Sci Nutr 2021;9(9):5229–5243. DOI: 10.1002/fsn3.2299.
  123. Rueda R. The role of dietary gangliosides on immunity and the prevention of infection. Br J Nutr 2007;98 Suppl 1:S68–S73. DOI: 10.1017/S0007114507832946.
  124. Schnaar RL, Gerardy-Schahn R, Hildebrandt H. Sialic acids in the brain: Gangliosides and polysialic acid in nervous system development, stability, disease, and regeneration. Physiol Rev 2014;94(2):461–518. DOI: 10.1152/physrev.00033.2013.
  125. Bronnum H, Seested T, Hellgren LI, et al. Milk-derived GM(3) and GD(3) differentially inhibit dendritic cell maturation and effector functionalities. Scand J Immunol 2005;61(6):551–557. DOI: 10.1111/j.1365-3083.2005.01566.x.
  126. Palmano K, Rowan A, Guillermo R, et al. The role of gangliosides in neurodevelopment. Nutrients 2015;7(5):3891–3913. DOI: 10.3390/nu7053891.
  127. Gurnida DA, Rowan AM, Idjradinata P, et al. Association of complex lipids containing gangliosides with cognitive development of 6-month-old infants. Early Hum Dev 2012;88(8):595–601. DOI: 10.1016/j.earlhumdev.2012.01.003.
  128. Venkat M, Chia LW, Lambers TT. Milk polar lipids composition and functionality: A systematic review. Crit Rev Food Sci Nutr 2024;64(1):31–75. DOI: 10.1080/10408398.2022.2104211.
  129. Okuda T. Dietary control of ganglioside expression in mammalian tissues. Int J Mol Sci 2019;21(1):177. DOI: 10.3390/ijms21010177.
  130. Park EJ, Suh M, Thomson AB, et al. Dietary gangliosides increase the content and molecular percentage of ether phospholipids containing 20:4n-6 and 22:6n-3 in weanling rat intestine. J Nutr Biochem 2006;17(5):337–344. DOI: 10.1016/j.jnutbio.2005.08.005.
  131. Dewettinck K, Rombaut R, Thienpont N, et al. Nutritional and technological aspects of milk fat globule membrane material. Int Dairy J 2008;18(5):436–457. DOI: 10.1016/j.idairyj.2007.10.014.
  132. Gomez-Larrauri A, Presa N, Dominguez-Herrera A, et al. Role of bioactive sphingolipids in physiology and pathology. Essays Biochem 2020;64(3):579–589. DOI: 10.1042/EBC20190091.
  133. Lee M, Lee SY, Bae YS. Functional roles of sphingolipids in immunity and their implication in disease. Exp Mol Med 2023;55(6):1110–1130. DOI: 10.1038/s12276-023-01018-9.
  134. Obinata H, Hla T. Sphingosine 1-phosphate and inflammation. Int Immunol 2019;31(9):617–625. DOI: 10.1093/intimm/dxz037.
  135. Et-Thakafy O, Guyomarc'h F, Lopez C. Lipid domains in the milk fat globule membrane: Dynamics investigated in situ in milk in relation to temperature and time. Food Chem 2017;220:352–361. DOI: 10.1016/j.foodchem.2016.10.017.
  136. Dei Cas M, Paroni R, Signorelli P, et al. Human breast milk as source of sphingolipids for newborns: Comparison with infant formulas and commercial cow's milk. J Transl Med 2020;18(1):481. DOI: 10.1186/s12967-020-02641-0.
  137. Maceyka M, Spiegel S. Sphingolipid metabolites in inflammatory disease. Nature 2014;510(7503):58–67. DOI: 10.1038/nature13475.
  138. Tanaka K, Hosozawa M, Kudo N, et al. The pilot study: Sphingomyelin-fortified milk has a positive association with the neurobehavioural development of very low birth weight infants during infancy, randomized control trial. Brain Dev 2013;35(1):45–52. DOI: 10.1016/j.braindev.2012.03.004.
  139. Tayebati SK, Amenta F. Choline-containing phospholipids: Relevance to brain functional pathways. Clin Chem Lab Med 2013;51(3):513–521. DOI: 10.1515/cclm-2012-0559.
  140. Derbyshire E, Obeid R. Choline, neurological development and brain function: A systematic review focusing on the first 1000 days. Nutrients 2020;12(6):1731. DOI: 10.3390/nu12061731.
  141. Addis MF, Pisanu S, Ghisaura S, et al. Proteomics and pathway analyses of the milk fat globule in sheep naturally infected by Mycoplasma agalactiae provide indications of the in vivo response of the mammary epithelium to bacterial infection. Infect Immun. 2011;79(9):3833–3845. DOI: 10.1128/IAI.00040-11.
  142. Reinhardt TA, Sacco RE, Nonnecke BJ, et al. Bovine milk proteome: Quantitative changes in normal milk exosomes, milk fat globule membranes and whey proteomes resulting from Staphylococcus aureus mastitis. J Proteomics 2013;82:141–154. DOI: 10.1016/j.jprot.2013.02.013.
  143. Hewelt-Belka W, Garwolinska D, Mlynarczyk M, et al. Comparative lipidomic study of human milk from different lactation stages and milk formulas. Nutrients 2020;12(7):2165. DOI: 10.3390/nu12072165.
  144. Yaron S, Shachar D, Abramas L, et al. Effect of high beta-palmitate content in infant formula on the intestinal microbiota of term infants. J Pediatr Gastroenterol Nutr 2013;56(4):376–381. DOI: 10.1097/MPG.0b013e31827e1ee2.
  145. Le Huerou-Luron I, Bouzerzour K, Ferret-Bernard S, et al. A mixture of milk and vegetable lipids in infant formula changes gut digestion, mucosal immunity and microbiota composition in neonatal piglets. Eur J Nutr 2018;57(2):463–476. DOI: 10.1007/s00394-016-1329-3.
  146. Liao Y, Alvarado R, Phinney B, et al. Proteomic characterization of human milk fat globule membrane proteins during a 12 month lactation period. J Proteome Res 2011;10(8):3530–3541. DOI: 10.1021/pr200149t.
  147. Afrache H, Gouret P, Ainouche S, et al. The butyrophilin (BTN) gene family: From milk fat to the regulation of the immune response. Immunogenetics 2012;64(11):781–794. DOI: 10.1007/s00251-012-0619-z.
  148. Ogg SL, Weldon AK, Dobbie L, et al. Expression of butyrophilin (Btn1a1) in lactating mammary gland is essential for the regulated secretion of milk-lipid droplets. Proc Natl Acad Sci USA 2004;101(27): 10084–10089. DOI: 10.1073/pnas.0402930101.
  149. Chen W, Zhang Z, Zhang S, et al. MUC1: Structure, function, and clinic application in epithelial cancers. Int J Mol Sci 2021;22(12):6567. DOI: 10.3390/ijms22126567.
  150. Martin HM, Hancock JT, Salisbury V, et al. Role of xanthine oxidoreductase as an antimicrobial agent. Infect Immun 2004;72(9):4933–4939. DOI: 10.1128/IAI.72.9.4933-4939.2004.
  151. Yi YS. Functional role of milk fat globule-epidermal growth factor VIII in macrophage-mediated inflammatory responses and inflammatory/autoimmune diseases. Mediators Inflamm 2016;2016:5628486. DOI: 10.1155/2016/5628486.
  152. Xu H, Diolintzi A, Storch J. Fatty acid-binding proteins: Functional understanding and diagnostic implications. Curr Opin Clin Nutr Metab Care 2019;22(6):407–412. DOI: 10.1097/MCO.0000000000000600.
  153. Demmelmair H, Prell C, Timby N, et al. Benefits of lactoferrin, osteopontin and milk fat globule membranes for infants. Nutrients 2017;9(8):817. DOI: 10.3390/nu9080817.
  154. Liu B, Newburg DS. Human milk glycoproteins protect infants against human pathogens. Breastfeed Med 2013;8(4):354–362. DOI: 10.1089/bfm.2013.0016.
  155. Singh SB, Carroll-Portillo A, Coffman C, et al. Intestinal alkaline phosphatase exerts anti-inflammatory effects against lipopolysaccharide by inducing autophagy. Sci Rep 2020;10(1):3107. DOI: 10.1038/s41598-020-59474-6.
  156. Kotozaki Y, Satoh M, Nasu T, et al. Human plasma xanthine oxidoreductase activity in cardiovascular disease: Evidence from a population-based study. Biomedicines 2023;11(3):754. DOI: 10.3390/biomedicines11030754.
  157. Honvo-Houeto E, Henry C, Chat S, et al. The endoplasmic reticulum and casein-containing vesicles contribute to milk fat globule membrane. Mol Biol Cell 2016;27(19):2946–2964. DOI: 10.1091/mbc.E16-06-0364.
  158. Wedekind SIS, Shenker NS. Antiviral properties of human milk. Microorganisms 2021;9(4):715. DOI: 10.3390/microorganisms 9040715.
  159. Martin Carli JF, Dzieciatkowska M, Hernandez TL, et al. Comparative proteomic analysis of human milk fat globules and paired membranes and mouse milk fat globules identifies core cellular systems contributing to mammary lipid trafficking and secretion. Front Mol Biosci 2023;10:1259047. DOI: 10.3389/fmolb.2023.1259047.
  160. Almeida CC, Mendonca Pereira BF, Leandro KC, et al. Bioactive compounds in infant formula and their effects on infant nutrition and health: A systematic literature review. Int J Food Sci 2021;2021:8850 080. DOI: 10.1155/2021/8850080.
  161. Zhang Y, Zhang X, Mi L, et al. Comparative proteomic analysis of proteins in breast milk during different lactation periods. Nutrients 2022;14(17):3648. DOI: 10.3390/nu14173648.
  162. Janiszewska E, Kmieciak A, Kacperczyk M, et al. The influence of clusterin glycosylation variability on selected pathophysiological processes in the human body. Oxid Med Cell Longev 2022;2022: 7657876. DOI: 10.1155/2022/7657876.
  163. Melnik BC, Schmitz G. Milk's role as an epigenetic regulator in health and disease. Diseases 2017;5(1):12. DOI: 10.3390/diseases5010012.
  164. Carrillo-Lozano E, Sebastian-Valles F, Knott-Torcal C. Circulating microRNAs in breast milk and their potential impact on the infant. Nutrients 2020;12(10):3066. DOI: 10.3390/nu12103066.
  165. Innis SM, Dyer R. Dietary triacylglycerols with palmitic acid (16:0) in the 2-position increase 16:0 in the 2-position of plasma and chylomicron triacylglycerols, but reduce phospholipid arachidonic and docosahexaenoic acids, and alter cholesteryl ester metabolism in formula-Fed piglets. J Nutr 1997;127(7):1311–1319. DOI: 10.1093/jn/127.7.1311.
  166. Baldi A, Pinotti L. Lipophilic microconstituents of milk. Adv Exp Med Biol 2008;606:109–125. DOI: 10.1007/978-0-387-74087-4_3.
  167. Hamosh M. The role of lingual lipase in neonatal fat digestion. Ciba Found Symp 1979(70):69–98. DOI: 10.1002/9780470720530.ch5.
  168. Smith LJ, Kaminsky S, D'Souza SW. Neonatal fat digestion and lingual lipase. Acta Paediatr Scand 1986;75(6):913–918. DOI: 10.1111/j.1651-2227.1986.tb103
PDF Share
PDF Share

© Jaypee Brothers Medical Publishers (P) LTD.