scholarly journals Genomics of Postprandial Lipidomics in the Genetics of Lipid-Lowering Drugs and Diet Network Study

Nutrients ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 4000
Author(s):  
Marguerite R. Irvin ◽  
May E. Montasser ◽  
Tobias Kind ◽  
Sili Fan ◽  
Dinesh K. Barupal ◽  
...  
Keyword(s):  
Arachidonic Acid ◽  
Fatty Acid ◽  
Fatty Acid Desaturase ◽  
Lipid Lowering ◽  
Chromosome 11 ◽  
High Fat ◽  
Lipid Lowering Drugs ◽  
Lipid Species ◽  
Lipid Response ◽  
Fat Meal

Postprandial lipemia (PPL) is an important risk factor for cardiovascular disease. Inter-individual variation in the dietary response to a meal is known to be influenced by genetic factors, yet genes that dictate variation in postprandial lipids are not completely characterized. Genetic studies of the plasma lipidome can help to better understand postprandial metabolism by isolating lipid molecular species which are more closely related to the genome. We measured the plasma lipidome at fasting and 6 h after a standardized high-fat meal in 668 participants from the Genetics of Lipid-Lowering Drugs and Diet Network study (GOLDN) using ultra-performance liquid chromatography coupled to (quadrupole) time-of-flight mass spectrometry. A total of 413 unique lipids were identified. Heritable and responsive lipid species were examined for association with single-nucleotide polymorphisms (SNPs) genotyped on the Affymetrix 6.0 array. The most statistically significant SNP findings were replicated in the Amish Heredity and Phenotype Intervention (HAPI) Heart Study. We further followed up findings from GOLDN with a regional analysis of cytosine-phosphate-guanine (CpGs) sites measured on the Illumina HumanMethylation450 array. A total of 132 lipids were both responsive to the meal challenge and heritable in the GOLDN study. After correction for multiple testing of 132 lipids (α = 5 × 10−8/132 = 4 × 10−10), no SNP was statistically significantly associated with any lipid response. Four SNPs in the region of a known lipid locus (fatty acid desaturase 1 and 2/FADS1 and FADS2) on chromosome 11 had p < 8.0 × 10−7 for arachidonic acid FA(20:4). Those SNPs replicated in HAPI Heart with p < 3.3 × 10−3. CpGs around the FADS1/2 region were associated with arachidonic acid and the relationship of one SNP was partially mediated by a CpG (p = 0.005). Both SNPs and CpGs from the fatty acid desaturase region on chromosome 11 contribute jointly and independently to the diet response to a high-fat meal.

scholarly journals An exome-wide sequencing study of lipid response to high-fat meal and fenofibrate in Caucasians from the GOLDN cohort

2018 ◽  
Vol 59 (4) ◽  
pp. 722-729 ◽  
Author(s):  
Xin Geng ◽  
Marguerite R. Irvin ◽  
Bertha Hidalgo ◽  
Stella Aslibekyan ◽  
Vinodh Srinivasasainagendra ◽  
...  
Keyword(s):  
Rare Variants ◽  
Transcript Level ◽  
Lipid Lowering ◽  
Gene Transcript ◽  
High Fat ◽  
Heart Study ◽  
Lipid Response ◽  
Coding Variants ◽  
Fat Meal ◽  
Meal Challenge

Our understanding of genetic influences on the response of lipids to specific interventions is limited. In this study, we sought to elucidate effects of rare genetic variants on lipid response to a high-fat meal challenge and fenofibrate (FFB) therapy in the Genetics of Lipid Lowering Drugs and Diet Network (GOLDN) cohort using an exome-wide sequencing-based association study. Our results showed that the rare coding variants in ITGA7, SIPA1L2, and CEP72 are significantly associated with fasting LDL cholesterol response to FFB (P = 1.24E-07), triglyceride postprandial area under the increase (AUI) (P = 2.31E-06), and triglyceride postprandial AUI response to FFB (P = 1.88E-06), respectively. We sought to replicate the association for SIPA1L2 in the Heredity and Phenotype Intervention (HAPI) Heart Study, which included a high-fat meal challenge but not FFB treatment. The associated rare variants in GOLDN were not observed in the HAPI Heart study, and thus the gene-based result was not replicated. For functional validation, we found that gene transcript level of SIPA1L2 is associated with triglyceride postprandial AUI (P < 0.05) in GOLDN. Our study suggests unique genetic mechanisms contributing to the lipid response to the high-fat meal challenge and FFB therapy.

scholarly journals Genome-wide association study of triglyceride response to a high-fat meal among participants of the NHLBI Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)

Metabolism ◽  
2015 ◽  
Vol 64 (10) ◽  
pp. 1359-1371 ◽  
Author(s):  
Mary K. Wojczynski ◽  
Laurence D. Parnell ◽  
Toni I. Pollin ◽  
Chao Q. Lai ◽  
Mary F. Feitosa ◽  
...  
Keyword(s):  
Association Study ◽  
Genome Wide Association Study ◽  
Genome Wide Association ◽  
Lipid Lowering ◽  
High Fat ◽  
Lipid Lowering Drugs ◽  
Genome Wide ◽  
Fat Meal

scholarly journals High-fat meal effect on LDL, HDL, and VLDL particle size and number in the Genetics of Lipid-Lowering drugs and diet network (GOLDN): an interventional study

2011 ◽  
Vol 10 (1) ◽  
pp. 181 ◽  
Author(s):  
Mary K Wojczynski ◽  
Stephen P Glasser ◽  
Albert Oberman ◽  
Edmond K Kabagambe ◽  
Paul N Hopkins ◽  
...  
Keyword(s):  
Particle Size ◽  
Lipid Lowering ◽  
High Fat ◽  
Interventional Study ◽  
Lipid Lowering Drugs ◽  
Vldl Particle ◽  
Meal Effect ◽  
Fat Meal

scholarly journals Heat stress elicits remodeling in the anther lipidome of peanut

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Zolian S. Zoong Lwe ◽  
Ruth Welti ◽  
Daniel Anco ◽  
Salman Naveed ◽  
Sachin Rustgi ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Heat Stress ◽  
Fatty Acid ◽  
Membrane Lipids ◽  
Fatty Acid Desaturase ◽  
Susceptible Genotype ◽  
Unsaturated Lipid ◽  
Lipid Species ◽  
Lipid Unsaturation ◽  
Fatty Acid Amount

AbstractUnderstanding the changes in peanut (Arachis hypogaea L.) anther lipidome under heat stress (HT) will aid in understanding the mechanisms of heat tolerance. We profiled the anther lipidome of seven genotypes exposed to ambient temperature (AT) or HT during flowering. Under AT and HT, the lipidome was dominated by phosphatidylcholine (PC), phosphatidylethanolamine (PE), and triacylglycerol (TAG) species (> 50% of total lipids). Of 89 lipid analytes specified by total acyl carbons:total carbon–carbon double bonds, 36:6, 36:5, and 34:3 PC and 34:3 PE (all contain 18:3 fatty acid and decreased under HT) were the most important lipids that differentiated HT from AT. Heat stress caused decreases in unsaturation indices of membrane lipids, primarily due to decreases in highly-unsaturated lipid species that contained 18:3 fatty acids. In parallel, the expression of Fatty Acid Desaturase 3-2 (FAD3-2; converts 18:2 fatty acids to 18:3) decreased under HT for the heat-tolerant genotype SPT 06-07 but not for the susceptible genotype Bailey. Our results suggested that decreasing lipid unsaturation levels by lowering 18:3 fatty-acid amount through reducing FAD3 expression is likely an acclimation mechanism to heat stress in peanut. Thus, genotypes that are more efficient in doing so will be relatively more tolerant to HT.

Abstract P132: Increased Cardiovascular Parasympathetic Tone in African Americans With CD36 Partial Deficiency

Hypertension ◽  
2017 ◽  
Vol 70 (suppl_1) ◽  
Author(s):  
Shahram Ejtemaei Mehr
Keyword(s):  
Heart Rate ◽  
Fatty Acid ◽  
African Americans ◽  
Heart Function ◽  
Taste Perception ◽  
Acid Uptake ◽  
High Fat ◽  
Cd36 Deficiency ◽  
Parasympathetic Tone ◽  
Fat Meal

Cardiovascular disease is the leading cause of death among African Americans (AA). Reduced parasympathetic tone as measured by high frequency heart rate variability (HF RRI ) predicts cardiovascular mortality. HF RRI is reduced after a high fat meal through caveolar sequestration of muscarinic M2 receptors. The fatty acid translocase CD36 is a protein abundant in the myocardium and important for heart function and lipid metabolism. CD36 plasma membrane localization and function in fatty acid uptake is modulated by its interaction with caveolin. One in four AAs are G-allele carriers for CD36 SNP rs3211938 resulting in ~50% decreased CD36 expression. CD36 deficiency also reduces fat taste perception, which might lead to higher fat intake to reach taste saturation. We tested the hypothesis that obese AAs with partial CD36 deficiency have altered parasympathetic tone during fasting and after a high-fat meal. We recruited 13 G-allele carriers and 39 non-carriers. Subjects were matched by age (P=0.820), BMI (P=0.751), and blood pressure (P=0.701). There was a trend towards reduction in heart rate in carriers (P=0.07). Baseline HF RRI was elevated in G carriers (557.1 [251 to 942] vs. 224 [95 to 655] ms 2 , P=0.046). Eleven subjects received a high-fat meal (700 Cal/m 2 BSA, 80% fat). HF RRI was measured at baseline and 30, 60, 120, 240 minutes after meal. Non-carriers (n=4) showed a time-dependent decline in the percent change in HF RRI (-23, -32, -70, -84, respectively). In G-allele carriers (N=6), the decline in HF RRI (21, -11, -61, -70 min) was attenuated. Conclusion: AAs with partial CD36 deficiency have enhanced fasting parasympathetic tone and a blunted response to a high fat meal.

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