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Title: De novo synthesis of milk triglycerides in humans

item MOHAMMAD, MAHMOUD - Children'S Nutrition Research Center (CNRC)
item SUNEHAG, AGNETA - Children'S Nutrition Research Center (CNRC)
item HAYMOND, MOREY - Children'S Nutrition Research Center (CNRC)

Submitted to: American Journal of Physiology - Endocrinology and Metabolism
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 2/3/2014
Publication Date: 4/1/2014
Citation: Mohammad, M.A., Sunehag, A.L., Haymond, M.W. 2014. De novo synthesis of milk triglycerides in humans. American Journal of Physiology - Endocrinology and Metabolism. 306(7):E838-E847.

Interpretive Summary: Breast milk fat consists of 98% triglycerides and provides nearly half of the energy needs of the infant. The triglyceride molecule is composed of three fatty acid molecules bound to a glycerol backbone molecule. Fat is metabolized differently based on the size of the fatty acid molecule. Short and medium chain sized fatty acids (equal to or less than 14 carbons) compared to longer ones (equal to or more than 16 carbons) are absorbed directly, rapidly burned and induce more satiety. Milk triglycerides contain fatty acids that are derived from three sources: synthesis within the mammary gland, dietary lipids, and body fat stores. In animals, mammary gland fat synthesis contributes significantly to milk fat depending on the animal species and its diet composition. However, very little is known regarding these processes in humans. In the present study, we developed a technique that measured the incorporation of 13C from [U-13C]glucose into specific milk and blood fats which are newly synthesized triglycerides within the breast. We studied healthy women following an overnight fast and during feeding of either a high fat diet or a high carbohydrate diet. This study demonstrated that the human mammary gland is capable of synthesizing fat of the medium and short forms and this is affected by the composition of the diet of the mother. Therefore, it is possible to modify the composition of human milk lipid to fit with the needs of the infant through changes in mother’s diet.

Technical Abstract: Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. Objective: To test the hypothesis that the incorporation of 13C carbons from [U-13C]glucose into fatty acids (FA) and glycerol in triglycerides (TG) will be greater: 1) in milk than plasma TG, 2) during a high-carbohydrate (H-CHO) diet than high-fat (HFAT) diet, and 3) during feeding than fasting. Seven healthy, lactating women were studied on two isocaloric, isonitrogenous diets. On one occasion, subjects received diets containing H-FAT or H-CHO diet for 1 wk. Incorporation of 13C from infused [U-13C]glucose into FA and glycerol was measured using GC-MS and gene expression in RNA isolated from milk fat globule using microarrays. Incorporation of 13C2 into milk FA increased with increased FA chain length from C2:0 to C12:0 but progressively declined in C14:0 and C16:0 and was not detected in FA>C16. During feeding, regardless of diets, enrichment of 13C2 in milk FA and 13C3 in milk glycerol were ~3- and ~7-fold higher compared with plasma FA and glycerol, respectively. Following an overnight fast during H-CHO and H-FAT diets, 25 and 6%, respectively, of medium-chain FA (MCFA, C6–C12) in milk were derived from glucose but increased to 75 and 25% with feeding. Expression of genes involved in FA or glycerol synthesis was unchanged regardless of diet or fast/fed conditions. The human MG is capable of de novo lipogenesis of primarily MCFA and glycerol, which is influenced by the macronutrient composition of the maternal diet.