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Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans.

ABSTRACT: Dietary consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against cardiometabolic disease through modulation of systemic and adipose inflammation. However, it is often difficult to detect the subtle effects of n-3 PUFA on inflammatory biomarkers in traditional intervention studies. We aimed to identify novel n-3 PUFA modulated gene expression using unbiased adipose transcriptomics during evoked endotoxemia in a clinical trial of n-3 PUFA supplementation. We analyzed adipose gene expression using RNA sequencing in the fenofibrate and omega-3 fatty acid modulation of endotoxemia (FFAME) trial of healthy individuals at three timepoints: before and after n-3 PUFA supplementation (n=8; 3600mg/day EPA/DHA) for 6weeks compared with placebo (n=6), as well as during a subsequent evoked inflammatory challenge (lipopolysaccharide 0.6ng/kg i.v.). As expected, supplementation with n-3 PUFA vs. placebo alone had only modest effects on adipose tissue gene expression, e.g., increased expression of immediate early response IER2. In contrast, the transcriptomic response to evoked endotoxemia was significantly modified by n-3 PUFA supplementation, with several genes demonstrating significant n-3 PUFA gene-nutrient interactions, e.g., enhanced transcriptional responses in specific immune genes IER5L, HES1, IL1RN, CCL18, IL1RN, IL7R, IL8, CCL3 and others. These data highlight potential mechanisms whereby n-3 PUFA consumption may enhance the immune response to an inflammatory challenge. In conclusion, unbiased transcriptomics during evoked inflammation reveals novel immune modulating functions of n-3 PUFA nutritional intervention in a dynamic pathophysiological setting.

SUBMITTER: Ferguson JF

PROVIDER: S-EPMC4808243 | biostudies-literature | 2016 Apr

REPOSITORIES: biostudies-literature

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Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans.

Ferguson Jane F JF Xue Chenyi C Hu Yu Y Li Mingyao M Reilly Muredach P MP

The Journal of nutritional biochemistry 20160111

Dietary consumption of long-chain omega-3 polyunsaturated fatty acids (n-3 PUFA) may protect against cardiometabolic disease through modulation of systemic and adipose inflammation. However, it is often difficult to detect the subtle effects of n-3 PUFA on inflammatory biomarkers in traditional intervention studies. We aimed to identify novel n-3 PUFA modulated gene expression using unbiased adipose transcriptomics during evoked endotoxemia in a clinical trial of n-3 PUFA supplementation. We ana ...[more]

PMID: 27012629

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Project description:BackgroundSelenium (Se) is a nutritionally essential trace element and health may be improved by increased Se intake. Previous kinetic studies have shown differences in metabolism of organic vs. inorganic forms of Se [e.g., higher absorption of selenomethionine (SeMet) than selenite (Sel), and more recycling of Se from SeMet than Sel]. However, the effects on Se metabolism after prolonged Se supplementation are not known.ObjectiveTo determine how the metabolism and transport of Se changes in the whole-body in response to Se-supplementation by measuring Se kinetics before and after 2 years of Se supplementation with SeMet.MethodsWe compared Se kinetics in humans [n = 31, aged 40 ± 3 y (mean ± SEM)] studied twice after oral tracer administration; initially (PK1), then after supplementation for 2 y with 200 µg/d of Se as selenomethionine (SeMet) (PK2). On each occasion, we administered two stable isotope tracers of Se orally: SeMet, the predominant food form, and selenite (Na2 76SeO3, or Sel), an inorganic form. Plasma and RBC were sampled for 4 mo; urine and feces were collected for the initial 12 d of each period. Samples were analyzed for tracers and total Se by isotope dilution GC-MS. Data were analyzed using a compartmental model, we published previously, to estimate fractional transfer between pools and pool masses in PK2.ResultsWe report that fractional absorption of SeMet or Sel do not change with SeMet supplementation and the amount of Se absorbed increased. The amount of Se excreted in urine increases but does not account for all the Se absorbed. As a result, there is a net incorporation of SeMet into various body pools. Nine of the 11 plasma pools doubled in PK2; two did not change. Differences in metabolism were observed for SeMet and Sel; RBC uptake increased 247% for SeMet, urinary excretion increased from two plasma pools for Sel and from two different pools for SeMet, and recycling to liver/tissues increased from one plasma pool for Sel and from two others for SeMet. One plasma pool increased more in males than females in PK2.ConclusionsOf 11 Se pools identified kinetically in human plasma, two did not increase in size after SeMet supplementation. These pools may be regulated and important during low Se intake.

Project description:Glycogen metabolism has emerged as a mediator in the control of energy homeostasis and studies in murine models reveal that adipose tissue might contain glycogen stores. Here we investigated the physio(patho)logical role of glycogen in human adipose tissue in the context of obesity and insulin resistance.We studied glucose metabolic flux of hypoxic human adipoctyes by nuclear magnetic resonance and mass spectrometry-based metabolic approaches. Glycogen synthesis and glycogen content in response to hypoxia was analyzed in human adipocytes and macrophages. To explore the metabolic effects of enforced glycogen deposition in adipocytes and macrophages, we overexpressed PTG, the only glycogen-associated regulatory subunit (PP1-GTS) reported in murine adipocytes. Adipose tissue gene expression analysis was performed on wild type and homozygous PTG KO male mice. Finally, glycogen metabolism gene expression and glycogen accumulation was analyzed in adipose tissue, mature adipocytes and resident macrophages from lean and obese subjects with different degrees of insulin resistance in 2 independent cohorts.We show that hypoxia modulates glucose metabolic flux in human adipocytes and macrophages and promotes glycogenesis. Enforced glycogen deposition by overexpression of PTG re-orients adipocyte secretion to a pro-inflammatory response linked to insulin resistance and monocyte/lymphocyte migration. Furthermore, glycogen accumulation is associated with inhibition of mTORC1 signaling and increased basal autophagy flux, correlating with greater leptin release in glycogen-loaded adipocytes. PTG-KO mice have reduced expression of key inflammatory genes in adipose tissue and PTG overexpression in M0 macrophages induces a pro-inflammatory and glycolytic M1 phenotype. Increased glycogen synthase expression correlates with glycogen deposition in subcutaneous adipose tissue of obese patients. Glycogen content in subcutaneous mature adipocytes is associated with BMI and leptin expression.Our data establish glycogen mishandling in adipose tissue as a potential key feature of inflammatory-related metabolic stress in human obesity.

Dataset Information

Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans.

Publications

Adipose tissue RNASeq reveals novel gene-nutrient interactions following n-3 PUFA supplementation and evoked inflammation in humans.

Similar Datasets

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