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Effects of diet and development on the Drosophila lipidome.

ABSTRACT: Cells produce tens of thousands of different lipid species, but the importance of this complexity in vivo is unclear. Analysis of individual tissues and cell types has revealed differences in abundance of individual lipid species, but there has been no comprehensive study comparing tissue lipidomes within a single developing organism. Here, we used quantitative shotgun profiling by high-resolution mass spectrometry to determine the absolute (molar) content of 250 species of 14 major lipid classes in 6 tissues of animals at 27 developmental stages raised on 4 different diets. Comparing these lipidomes revealed unexpected insights into lipid metabolism. Surprisingly, the fatty acids present in dietary lipids directly influence tissue phospholipid composition throughout the animal. Furthermore, Drosophila differentially regulates uptake, mobilization and tissue accumulation of specific sterols, and undergoes unsuspected shifts in fat metabolism during larval and pupal development. Finally, we observed striking differences between tissue lipidomes that are conserved between phyla. This study provides a comprehensive, quantitative and expandable resource for further pharmacological and genetic studies of metabolic disorders and molecular mechanisms underlying dietary response.

SUBMITTER: Carvalho M

PROVIDER: S-EPMC3421444 | biostudies-other | 2012

REPOSITORIES: biostudies-other

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Effects of diet and development on the Drosophila lipidome.

Carvalho Maria M Sampaio Julio L JL Palm Wilhelm W Brankatschk Marko M Eaton Suzanne S Shevchenko Andrej A

Molecular systems biology 20120101

Cells produce tens of thousands of different lipid species, but the importance of this complexity in vivo is unclear. Analysis of individual tissues and cell types has revealed differences in abundance of individual lipid species, but there has been no comprehensive study comparing tissue lipidomes within a single developing organism. Here, we used quantitative shotgun profiling by high-resolution mass spectrometry to determine the absolute (molar) content of 250 species of 14 major lipid classe ...[more]

PMID: 22864382

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Project description:ObjectivesThe fatty acid (FA) composition of breast milk is a relevant aspect related to the development of the lactating infant. The present study aimed at exploring correlations between dietary intake of macro- and micronutrients with the FA profile in breast milk, and the possible implication for infants' growth.Study designBreast milk samples from a cohort of lactating women were collected 7-15 days postpartum. The FA profiles in triacylglycerol (TAG) and phospholipid (PL)-rich fractions were analyzed by gas chromatography. Diet was registered during the third trimester of pregnancy by means of a food frequency questionnaire (FFQ). In addition, anthropometric measurements of infants were collected from gestation and up to 12 months postpartum.ResultsThe FA profile in breast milk was characterized by a median of 37.4, 41.3 and 16.8% of saturated, monounsaturated, and polyunsaturated FAs, respectively. From the dietary components, zinc, iron, and B group vitamins were correlated positively with the proportion of total n-3 FAs in TAG and C20:5 n-3 in PL. Lycopene, vitamin E, zinc, and vitamin B2 showed a similar correlation with total polyunsaturated fatty acid (PUFA), total n-6 FAs, C20:4 n-6, and C18:2 n-6 in TAG. Regarding food groups, nuts showed the strongest association with several PUFA both in TAG and PL, while the vegetable group was also positively associated with C18:3 n-3. Furthermore, the concentration of linolenic acid (C18:3 n-3) and palmitic acid (C16:0) were positively associated with increased length for age (LFA) and weight for age (WFA) at 12 months compared with birth [ΔLFA -0.16 (-0.85, 0.37); ΔWFA -0.26 (-0.77, 0.21)].ConclusionsMothers' intake of nuts, dietary sources of zinc, iron, and B group vitamins were identified as potential predictors of a high-unsaturated FA profile in breast milk. In addition, linolenic and palmitic acids in breast milk were positively associated with infants' growth in the first year of life.

Project description:IntroductionEpidemiological studies linking dietary fat intake and obesity to breast cancer risk have produced inconsistent results. This may be due to the difficulty of dissociating fat intake from obesity, and/or the lack of defined periods of exposure in these studies. The pubertal mammary gland is highly sensitive to cancer-causing agents. We assessed how high fat diet (HFD) affects inflammation, proliferative, and developmental events in the pubertal gland, since dysregulation of these can promote mammary tumorigenesis. To test the effect of HFD initiated during puberty on tumorigenesis, we utilized BALB/c mice, for which HFD neither induces obesity nor metabolic syndrome, allowing dissociation of HFD effects from other conditions associated with HFD.MethodsPubertal BALB/c mice were fed a low fat diet (12% kcal fat) or a HFD (60% kcal fat), and subjected to carcinogen 7,12-dimethylbenz[a]anthracene (DMBA)-induced tumorigenesis.ResultsHFD elevated mammary gland expression of inflammatory and growth factor genes at 3 and 4 weeks of diet. Receptor activator of nuclear factor kappa-B ligand (RANKL), robustly induced at 4 weeks, has direct mitogenic activity in mammary epithelial cells and, as a potent inducer of NF-?B activity, may induce inflammatory genes. Three weeks of HFD induced a transient influx of eosinophils into the mammary gland, consistent with elevated inflammatory factors. At 10 weeks, prior to the appearance of palpable tumors, there were increased numbers of abnormal mammary epithelial lesions, enhanced cellular proliferation, increased growth factors, chemokines associated with immune-suppressive regulatory T cells, increased vascularization, and elevated M2 macrophages. HFD dramatically reduced tumor latency. Early developing tumors were more proliferative and were associated with increased levels of tumor-related growth factors, including increased plasma levels of HGF in tumor-bearing animals. Early HFD tumors also had increased vascularization, and more intra-tumor and stromal M2 macrophages.ConclusionsTaken together in this non-obesogenic context, HFD promotion of inflammatory processes, as well as local and systemically increased growth factor expression, are likely responsible for the enhanced tumorigenesis. It is noteworthy that although DMBA mutagenesis is virtually random in its targeting of genes in tumorigenesis, the short latency tumors arising in animals on HFD showed a unique gene expression profile, highlighting the potent overarching influence of HFD.

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Effects of diet and development on the Drosophila lipidome.

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Effects of diet and development on the Drosophila lipidome.

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