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High fat challenges with different fatty acids affect distinct atherogenic gene expression pathways in immune cells from lean and obese subjects

ABSTRACT: Early perturbations in vascular health can be detected by imposing subjects to a high fat (HF) challenge and measure response capacity. Subtle responses can be determined by assessment of whole-genome transcriptional changes. We aimed to magnify differences in health by comparing gene-expression changes in peripheral blood mononuclear cells (PBMCs) towards a high MUFA or SFA challenge between subjects with different cardiovascular disease risk profiles and to identify fatty-acid specific gene-expression pathways. METHODS AND RESULTS: In a cross-over study, 17 lean and 15 obese men (50-70y) received two 95g fat shakes, high in SFAs or MUFAs. PBMC gene-expression profiles were assessed fasted and 4h postprandially. Comparisons were made between groups and shakes. During fasting, 294 genes were significantly different expressed between lean and obese. The challenge increased differences to 607 genes after SFA and 2516 genes after MUFA. In both groups, SFA decreased expression of cholesterol biosynthesis and uptake genes and increased cholesterol efflux genes. MUFA increased inflammatory genes and PPARα targets involved in β-oxidation. CONCLUSION: Based upon gene-expression changes, we conclude that a HF challenge magnifies differences in health, especially after MUFA. Our findings also demonstrate how SFAs and MUFAs exert distinct effects on lipid handling pathways in immune cells.

ORGANISM(S): Homo sapiens

PROVIDER: GSE53232 | GEO | 2015/05/13

SECONDARY ACCESSION(S): PRJNA231185

REPOSITORIES: GEO

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High fat challenges with different fatty acids affect distinct atherogenic gene expression pathways in immune cells from lean and obese subjects

Project description:Early perturbations in vascular health can be detected by imposing subjects to a high fat (HF) challenge and measure response capacity. Subtle responses can be determined by assessment of whole-genome transcriptional changes. We aimed to magnify differences in health by comparing gene-expression changes in peripheral blood mononuclear cells (PBMCs) towards a high MUFA or SFA challenge between subjects with different cardiovascular disease risk profiles and to identify fatty-acid specific gene-expression pathways. METHODS AND RESULTS: In a cross-over study, 17 lean and 15 obese men (50-70y) received two 95g fat shakes, high in SFAs or MUFAs. PBMC gene-expression profiles were assessed fasted and 4h postprandially. Comparisons were made between groups and shakes. During fasting, 294 genes were significantly different expressed between lean and obese. The challenge increased differences to 607 genes after SFA and 2516 genes after MUFA. In both groups, SFA decreased expression of cholesterol biosynthesis and uptake genes and increased cholesterol efflux genes. MUFA increased inflammatory genes and PPAR? targets involved in ?-oxidation. CONCLUSION: Based upon gene-expression changes, we conclude that a HF challenge magnifies differences in health, especially after MUFA. Our findings also demonstrate how SFAs and MUFAs exert distinct effects on lipid handling pathways in immune cells. In a double-blind cross-over study, 17 lean and 15 obese men (aged 50-70y) received two high-fat milkshakes containing 95g fat, either high in saturated (SFA) or monounsaturated (MUFA) fatty acids. PBMC gene expression profiles were determined before and 4h after shake consumption.

2015-05-13 | E-GEOD-53232 | biostudies-arrayexpress

Dietary fat quality, more than dietary fat quantity, impacts genome-wide DNA methylation patterns in Greek preadolescents

Project description:The type and the amount of dietary fat have a significant influence on the metabolic pathways involved in the development of obesity, metabolic syndrome, diabetes type 2 and cardiovascular diseases. However, it is unknown to what extent this modulation is achieved through DNA methylation. We assessed the effects of cholesterol intake, the proportion of energy intake derived from fat, the ratio of polyunsaturated fatty acids (PUFA) to saturated fatty acids (SFA), the ratio of monounsaturated fatty acids (MUFA) to SFA, and the ratio of (MUFA+PUFA) to SFA on genome-wide DNA methylation patterns in normal-weight and obese children. We determined the genome-wide methylation profile in blood of 69 Greek preadolescents (~10 y old), as well as their dietary intake for two consecutive weekdays and one weekend day. The methylation levels of four sites and a CpG island were significantly correlated with total fat intake. The methylation levels of 13 islands and 16 sites were significantly correlated with PUFA/SFA; of 35 islands and 158 sites with MUFA/SFA; and of 50 islands and 130 sites with (MUFA+PUFA)/SFA. We found significant gene enrichment in 26 pathways for PUFA/SFA, including the leptin pathway, and a significant enrichment in three pathways for (MUFA+PUFA)/SFA. Our results suggest that the quality, and to a lesser extent the quantity of fat intake, influences DNA methylation, including genes involved in metabolism. Thus, specific changes in DNA methylation may play an important role in the mechanisms involved in the physiological responses to different types of dietary fat. Bisulphite converted DNA from 22 boys were hybridised to the Illumina Infinium 27k Human Methylation Beadchip v1.2.Both obese and normal-weight indiviudals were included.

2014-05-09 | E-GEOD-57484 | biostudies-arrayexpress

Dietary fat quality, more than dietary fat quantity, impacts genome-wide DNA methylation patterns in Greek preadolescents

2014-05-09 | GSE57484 | GEO

Effects of a diet high in monounsaturated fat and a full Mediterranean diet on PBMC whole genome gene expression and plasma proteins

Project description:This study aimed to identify the effects of replacement of saturated fat (SFA) by monunsaturated fat (MUFA) in a western-type diet and the effects of a full Mediterranean (MED) diet on whole genome PBMC gene expression and plasma protein profiles. Abdominally overweight subjects were randomized to a 8 wk completely controlled SFA-rich diet, a SFA-by-MUFA-replaced diet (MUFA diet) or a MED diet. Concentrations of 124 plasma proteins and PBMCs whole genome transcriptional profiles were assessed. Consumption of the MUFA and MED diet, compared with the SFA diet, decreased expression of oxidative phosphorylation (OXPHOS) genes, serum lipids and plasma Connective Tissue Growth Factor, myoglobin and Apo B concentrations. The MED diet additional lowered plasma α-2-macroglobulin concentration compared with the SFA diet. Within the MED diet group concentrations of several pro-inflammatory proteins were lowered. We conclude that MUFA as replacement of SFA in a western-type diet or in a MED diet had similar effects on lowering expression of OXPHOS genes. We hypothesize that replacement of SFA by MUFA increased metabolic health as reflected by lowered serum lipids and certain plasma proteins, thereby reducing metabolic stress and OXPHOS activity in PBMCs. The MED diet may have additional anti-atherogenic effects by lowering concentrations of pro-inflammatory plasma proteins.

2012-08-03 | GSE30509 | GEO

Effects of a diet high in monounsaturated fat and a full Mediterranean diet on PBMC whole genome gene expression and plasma proteins

Project description:This study aimed to identify the effects of replacement of saturated fat (SFA) by monunsaturated fat (MUFA) in a western-type diet and the effects of a full Mediterranean (MED) diet on whole genome PBMC gene expression and plasma protein profiles. Abdominally overweight subjects were randomized to a 8 wk completely controlled SFA-rich diet, a SFA-by-MUFA-replaced diet (MUFA diet) or a MED diet. Concentrations of 124 plasma proteins and PBMCs whole genome transcriptional profiles were assessed. Consumption of the MUFA and MED diet, compared with the SFA diet, decreased expression of oxidative phosphorylation (OXPHOS) genes, serum lipids and plasma Connective Tissue Growth Factor, myoglobin and Apo B concentrations. The MED diet additional lowered plasma Î±-2-macroglobulin concentration compared with the SFA diet. Within the MED diet group concentrations of several pro-inflammatory proteins were lowered. We conclude that MUFA as replacement of SFA in a western-type diet or in a MED diet had similar effects on lowering expression of OXPHOS genes. We hypothesize that replacement of SFA by MUFA increased metabolic health as reflected by lowered serum lipids and certain plasma proteins, thereby reducing metabolic stress and OXPHOS activity in PBMCs. The MED diet may have additional anti-atherogenic effects by lowering concentrations of pro-inflammatory plasma proteins. Expression profiling by array

2012-08-02 | E-GEOD-30509 | biostudies-arrayexpress

A saturated fatty acid rich diet can induce an 'obese-like' gene expression profile in adipose tissue

2010-02-14 | GSE14954 | GEO

A saturated fatty acid rich diet can induce an 'obese-like' gene expression profile in adipose tissue

Project description:We investigated the effect of a saturated (SFA) and a monounsaturated (MUFA) rich diet on insulin sensitivity and adipose tissue gene expression profiles of subjects at risk for metabolic syndrome. A controlled-feeding trial was performed with 20 moderately overweight subjects. Subjects received a SFA-rich or a MUFA-rich diet for 8 weeks. Subcutaneous adipose tissue samples were obtained and insulin sensitivity was measured. Whole genome micro-array analysis was performed on the adipose tissue samples. Consumption of a SFA-rich diet resulted in a pro-inflammatory 'obese-like' gene expression profile while consumption of a MUFA-rich diet caused a more anti-inflammatory profile. This suggests that replacement of dietary SFA by MUFA could prevent adipose tissue inflammation and may reduce the risk for inflammation related diseases such as the metabolic syndrome. In a parallel controlled feeding trial, subcutaneous adipose tissue samples were collected from moderately overweight human subjects at baseline and after 8 weeks consumption of either SFA-rich or MUFA-rich diets. RNA was isolated from the samples using Trizol and the Qiagen RNeasy Micro kit (Qiagen, Venlo, the Netherlands). RNA was was labeled using a one-cycle cDNA labeling kit (MessageAmpTM II-Biotin Enhanced Kit, Ambion, Inc.) and hybridized to Affymetrix NuGO_Hs1a52018 arrays.

2010-02-13 | E-GEOD-14954 | biostudies-arrayexpress

Effects of replacing saturated fat with polyunsaturated fat on whole genome gene expression profiles in peripheral blood mononuclear cells - a randomized controlled dietary intervention study

Project description:To further understand the molecular mechanisms underlying the health effects of replacing saturated fat (SFA) with polyunsaturated fat (PUFA), we aimed to explore the whole transcriptome response of peripheral blood mononuclear cells (PBMCs) in a dietary intervention where SFAs were replaced with PUFAs.

2021-06-03 | GSE176043 | GEO

Gene expression data from differentiated 3T3-L1 preadipocytes treated with Palmitic Acid, Stearic Acid, Palmitoleic Acid, or Oleic Acid

Project description:Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Global gene expression was examined in differentiated preadipocytes treated with either 250 μM PA, SA, PMA, or OA for 48 hrs. Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling, and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids.

2012-11-13 | GSE42220 | GEO

Gene expression data from differentiated 3T3-L1 preadipocytes treated with Palmitic Acid, Stearic Acid, Palmitoleic Acid, or Oleic Acid

Project description:Saturated fatty acids (SFA) are widely thought to induce inflammation in adipose tissue (AT), while monounsaturated fatty acids (MUFA) are purported to have the opposite effect; however, it is unclear if individual SFA and MUFA behave similarly. Our goal was to examine adipocyte transcriptional networks regulated by individual SFA (palmitic acid, PA; stearic acid, SA) and MUFA (palmitoleic acid, PMA; oleic acid, OA). Global gene expression was examined in differentiated preadipocytes treated with either 250 M-NM-<M PA, SA, PMA, or OA for 48 hrs. Individual fatty acid treatments had significant effects on adipocyte gene expression. Functional analyses revealed that PA induced the TLR signalling pathway, while PMA had the opposite effect. SA and OA had similar effects, with increases in key metabolic pathways including mTOR and PPAR signalling, and a reduction in TLR signalling. Ccl5 was validated as a candidate gene that may mediate the differential inflammatory effects of SFA and MUFA in AT. Individual SFA and MUFA trigger distinct transcriptional responses in differentiated preadipocytes, with inflammatory and metabolic pathways particularly sensitive to these fatty acids. A total of 4 microarrays were run for each FA treatment. We experienced difficulties with the cRNA amplification for one replicate from the OA treated cells; therefore this treatment group only had an n=3. For each sample, 100 ng of total RNA was prepared for hybridization to Affymetrix Mouse Gene 1.1 ST array strips, according to the manufacturerM-bM-^@M-^Ys instructions (Affymetrix Inc., Fremont, CA, USA).

2012-11-13 | E-GEOD-42220 | biostudies-arrayexpress

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