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Gene Expression in the Human Mammary Epithelium in response to consumption of high fat (H-FAT) and high carbohdyrate (H-CHO) diets.


ABSTRACT: Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans. We hypothesized that de novo lipogenesis, as reflected by incorporation of 13C carbons from [U-13C]glucose into fatty acids (FAs) and glycerol in triglycerides (TG), will be greater: a. in milk than plasma TG, b. during a high carbohydrate (H-CHO) diet than high fat (H-FAT) diet and c. during feeding than fasting. 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 week. Incorporation of 13C from infused [U-13C]glucose into FAs and glycerol was measured using GC/MS methodology and gene expression using RNA isolated from breast milk fat globule (MFG). Incorporation of 13C2 into milk FAs, increased with increased chain length of the FAs from C2:0 to C12:0 but progressively declined in C14:0 and C16:0 and was not detected in FAs >C16. During feeding, regardless of diets, enrichment of 13C2 in milk FA and 13C3 in milk glycerol were ~3 and ~7 fold higher compared to plasma FA and glycerol, respectively. Following an overnight fast during H-CHO and H-FAT diets study periods, 25% and 6%, respectively, of medium chain FAs (MCFAs, C6-C12) were derived from glucose but increased to 75% and 25% with feeding. The expression of genes involved in FA or glycerol synthesis pathways was unchanged regardless of diet or fast-fed conditions. Conclusions: The human MG is capable of de novo lipogenesis, of primarily MCFAs and glycerol, which is influenced by the macro-nutrient composition of the maternal diet. On day 7 of consumption of each of the two diets milk samples collected from 7 healthy, lean, exclusively breastfeeding women following an overnight fast and feeding conditions [7 x 2 x 2 = 28 samples] were processed for isotope enrichments and RNA isolation from the milk fat globules. The total RNA was utilized for microarray analyses.

ORGANISM(S): Homo sapiens

SUBMITTER: Mahmoud Mohammad 

PROVIDER: E-GEOD-51874 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

De novo synthesis of milk triglycerides in humans.

Mohammad Mahmoud A MA   Sunehag Agneta L AL   Haymond Morey W MW  

American journal of physiology. Endocrinology and metabolism 20140204 7


<h4>Unlabelled</h4>Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans.<h4>Objective</h4>To test the hypothesis that the incorporation of (13)C carbons from [U-(13)C]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 (H-FAT) diet, and 3) during feeding than fasting. Seven healthy, lactating women were studied on two i  ...[more]

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