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De novo synthesis of milk triglycerides in humans.

ABSTRACT: Mammary gland (MG) de novo lipogenesis contributes significantly to milk fat in animals but little is known in humans.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 isocaloric, isonitrogenous diets. On one occasion, subjects received diets containing H-FAT or H-CHO diet for 1 wk. Incorporation of (13)C from infused [U-(13)C]glucose into FA and glycerol was measured using GC-MS and gene expression in RNA isolated from milk fat globule using microarrays. Incorporation of (13)C2 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 (13)C2 in milk FA and (13)C3 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.

SUBMITTER: Mohammad MA

PROVIDER: S-EPMC3962611 | biostudies-literature | 2014 Apr

REPOSITORIES: biostudies-literature

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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]

PMID: 24496312

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Project description:Bovine milk is widely regarded as a nutritious food source for humans, although the effects of individual fatty acids on human health is a subject of debate. Based on the assumption that genomic selection offers potential to improve milk fat composition, there is strong interest to understand more about the genetic factors that influence the biosynthesis of bovine milk and the molecular mechanisms that regulate milk fat synthesis and secretion. For this reason, the work reported here aimed at identifying genetic variants that affect milk fatty acid composition in Norwegian Red cattle. Milk fatty acid composition was predicted from the nation-wide recording scheme using Fourier transform infrared spectroscopy data and applied to estimate heritabilities for 36 individual and combined fatty acid traits. The recordings were used to generate daughter yield deviations that were first applied in a genome-wide association (GWAS) study with 17,343 markers to identify quantitative trait loci (QTL) affecting fatty acid composition, and next on high-density and sequence-level datasets to fine-map the most significant QTL on BTA13 (BTA for Bos taurus chromosome).The initial GWAS revealed 200 significant associations, with the strongest signals on BTA1, 13 and 15. The BTA13 QTL highlighted a strong functional candidate gene for de novo synthesis of short- and medium-chained saturated fatty acids; acyl-CoA synthetase short-chain family member 2. However, subsequent fine-mapping using single nucleotide polymorphisms (SNPs) from a high-density chip and variants detected by resequencing showed that the effect was more likely caused by a second nearby gene; nuclear receptor coactivator 6 (NCOA6). These findings were confirmed with results from haplotype studies. NCOA6 is a nuclear receptor that interacts with transcription factors such as PPAR?, which is a major regulator of bovine milk fat synthesis.An initial GWAS revealed a highly significant QTL for de novo-synthesized fatty acids on BTA13 and was followed by fine-mapping of the QTL within NCOA6. The most significant SNPs were either synonymous or situated in introns; more research is needed to uncover the underlying causal DNA variation(s).

Dataset Information

De novo synthesis of milk triglycerides in humans.

Publications

De novo synthesis of milk triglycerides in humans.

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