Project description:<p>The GOLDN study was initiated to assess how genetic factors interact with environmental (diet and drug) interventions to influence blood levels of triglycerides and other atherogenic lipid species and inflammation markers (registered at <a href="http://clinicaltrials.gov/ct2/show/NCT00083369">clinicaltrails.gov</a>, number NCT00083369). The study recruited Caucasian participants primarily from three-generational pedigrees from two NHLBI Family Heart Study (FHS) field centers (Minneapolis, MN and Salt Lake City, UT). Only families with at least two siblings were recruited and only participants who did not take lipid-lowering agents (pharmaceuticals or nutraceuticals) for at least 4 weeks prior to the initial visit were included. A total of 1048 GOLDN participants were included in the diet intervention. The diet intervention followed the protocol of Patsch et al. (<a href="http://www.ncbi.nlm.nih.gov/pubmed/1420093">1992</a>). The whipping cream (83% fat) meal had 700 Calories/m2 body surface area (2.93 MJ/m2 body surface area): 3% of calories were derived from protein (instant nonfat dry milk) and 14% from carbohydrate (sugar). The ratio of polyunsaturated to saturated fat was 0.06 and the cholesterol content of the average meal was 240 mg. The mixture was blended with ice and flavorings. Blood samples were drawn immediately before (fasting) and at 3.5 and 6 hours after consuming the high-fat meal. For the GOLDN lipidomics study, sterols and fatty acids were measured from stored plasma (-80 degrees Celsius) collected at fasting and 3.5 hours after the diet intervention using TrueMass Panels from Lipomics (West Sacramento, CA). A total of 11 sterols were quantified in nmols/gram of sample including total cholesterol, 7-dehydrocholesterol, desmosterol, lanosterol, lathasterol, cholestanol, coprostanol, beta-sitosterol, campesterol, stigmasterol, and 7alpha-hydroxycholesterol. A total of 35 fatty acids were quantified in nmols/gram of sample inlcuding myristic acid (14:0); pentadecanoic acid (15:0); palmitic acid (16:0); stearic acid (18:0); arachidic acid (20:0); behenic acid (22:0); lignoceric acid (24:0); myristoleic acid (14:1n5); palmitoleic acid (16:1n7); palmitelaidic acid (t16:1n7); oleic acid (18:1n9); elaidic acid (t18:1n9); vaccenic acid (18:1n7); linoleic acid (18:2n6); gamma-linolenic acid (18:3n6); alpha-linolenic acid (18:3n3); stearidonic acid (18:4n3); eicosenoic acid (20:1n9); eicosadienoic acid (20:2n6); mead acid (20:3n9); di-homo-gamma-linolenic acid (20:3n6); arachidonic acid (20:4n6); eicsoatetraenoic acid (20:4n3); eicosapentaenoic acid (20:5n3); erucic acid (22:1n9); docosadienoic acid (22:2n6); adrenic acid (22:4n6); docosapentaenoic acid (22:5n6); docosapentaenoic acid (22:5n3); docosahexaenoic acid (22:6n3); nervonic acid (24:1n9); and plasmalogen derivatives of 16:0, 18:0, 18:1n9, and 18:1n7.</p>

Project description:We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis. Keywords: Diet intervention study Nine-week-old C57Bl/6J mice were fed a low-fat diet (LF-PO) and three different types of high-fat diet, based on palm oil (HF-PO; P/S1.0), olive oil (HF-OO; P/S4.6) and safflower oil (HF-SO; P/S10.1) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. After 2 weeks of diet intervention, 6 mice per high-fat diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on mucosal scrapings.

Project description:Background: Despite the established relation between energy restriction and metabolic health, the most beneficial nutrient composition of a weight-loss diet is still subject of debate. Objectives: The aim of the study was to examine the additional effects of nutrient quality on top of energy restriction(ER). Methods: A parallel-designed 12-week 25%ER dietary intervention study was conducted. Participants aged 40-70 years with abdominal obesity were randomized over three groups: a 25%ER high nutrient quality diet (n = 40); a 25%ER low nutrient quality diet (n = 40); or a habitual diet (n = 30). Both ER diets were nutritionally adequate, the high nutrient quality ER diet was enriched in monounsaturated and n-3 polyunsaturated fatty acids, fiber, and plant protein and reduced in fructose. Before and after the intervention intra-hepatic lipids, body fat distribution, fasting and postprandial responses to a mixed meal shake challenge test of cardio-metabolic risk factors, lipoproteins, vascular measurements, and adipose tissue transcriptome were assessed. Results: The high quality ER diet (-8.4 ± 3.2) induced 2.1 kg more weight loss (P = 0.007) than the low quality ER diet (-6.3 ± 3.9), reduced fasting serum total cholesterol (P = 0.014) and plasma triglycerides (P < 0.001), promoted an anti-atherogenic lipoprotein profile and induced a more pronounced decrease in adipose tissue gene expression of energy metabolism pathways than the low quality ER diet. Explorative analyses showed that the difference in weight loss between both ER diets were specifically present in insulin sensitive subjects (HOMA-IR ≤ 2.5), in whom the high nutrient quality diet induced 3.9 kg more weight loss than the low nutrient quality diet. Conclusion: A high nutrient quality 25%ER diet is more beneficial for cardiometabolic health than a low nutrient quality 25%ER diet. Overweight insulin sensitive subjects may benefit more from a high than a low nutrient quality ER diet with respect to weight loss, due to potential attenuation of glucose-induced lipid synthesis in adipose tissue. Trial registration: ClinicalTrials.gov NCT02194504.

Project description:Some studies have shown that acute intake of high-phenol virgin olive oil reduces pro-inflammatory, pro-oxidant and pro-thrombotic states, but nowadays still remains unclear if those effects attributed to its phenolic fraction could be exerted at transcriptional level in vivo. Two virgin olive oil-based breakfasts with high (398 ppm) and low (70 ppm) content of phenolic compounds were administered to twenty patients (9 men and 11 women) with metabolic syndrome following a double-blinded random crossover design. Prior to the first breakfast intervention, participants followed a 6-week washout period in which they were instructed to not take vitamins, soy supplements, or any drug. To eliminate the potential effect that might exist in their usual dietary habits, all subjects followed a low-fat, carbohydrate rich (CHO) diet during this period and untill the end of the study. In the 24 h before each breakfast intervention, participants were instructed to avoid consuming phenol-rich foods such as fruit or juices, wine, grape juice, chocolate, coffee, tea, olive oil, or soya, and to refrain from intense physical exercise during that period. After a 12 h fasting and following a randomized sequential crossover design with one-week washout period, participants reported to the hospital and received two fat meals consisting of 60 g of white bread, 40 mL of VOO (CANOLIVA®, Antonio Cano e Hijos™, Córdoba, Spain) with high (398 ppm) or low (70 ppm) content in phenolic compounds, and 60,000 IU of vitamin A per m2 of body surface. Olive oil with low content in phenolic compounds was obtained as a result of extraction by physical procedures of most of the phenolic compounds in the high-phenol olive oil, so that both oils kept a similar composition of the remaining macro- and micronutrients. Throughout the 4-h duration of the study, the subjects performed no physical activity, nor did they consume anything but water. Gene expression was performed on peripheral blood mononuclear cells (PBMCs) at postprandial period (4 hours after breakfast) by microarray analysis and verified by qRT-PCR. Two sets of dye-swaped experiments were performed making a total of four technical replicates per subject. Each of the hybridizations compared total RNA from PBMCs obtained 4h after the intake of virgin olive oil with high phenolic content vs. total RNA from PBMCs obtained 4h after low-phenol virgin olive oil consumption.

Project description:The prevalence of the metabolic syndrome (MS) is rapidly increasing all over the world. Consequently, there is an urgent need for more effective intervention strategies. Both animal and human studies indicate that lipid oversupply to skeletal muscle can result in insulin resistance which is one of the charecteristices of the MS. C57BL/6J mice were fed a low fat (10 kcal%) palm oil diet or a high fat (45 kcal%; HF) palm oil diet for 3 or 28 days. By combining transcriptomics with protein and lipid analyses we aimed to better understand the molecular events underlying the early onset of the MS. Short-term HF-feeding led to altered expression levels of genes involved in a variety of biological processes including morphogenesis, energy metabolism, lipogenesis and immune function. Protein analysis showed increased levels of the myosin heavy chain, slow fiber type protein and the complexes II, III, IV and V of the oxidative phosphorylation. Furthermore, we observed that the main mitochondrial membrane phospholipids, phosphatidylcholine and phosphatidylethanolamine, contained more saturated fatty acids. Altogether, these results point to a morphological as well as a metabolic adaptation by promoting a more oxidative fiber type. We hypothesize that after this early adaptation, a continued transcriptional down-regulation of genes involved in oxidative phosphorylation will result in decreased oxidative capacity at a later stage. Together with increased saturation of phospholipids of the mitochondrial membrane this can result in decreased mitochondrial function which is a hallmark observed in insulin resistance and type 2 diabetes. Keywords: diet intervention and time course In the present study we investigated the short versus the long term effects of a high fat diet on the mouse muscle transcriptome by performing a genome-wide analysis of high fat diet-responsive genes. C57BL/6J mice were fed a low fat (LF) diet (10 kcal% palm oil) or a high fat (HF) diet (45 kcal% palm oil) for 3 or 28 days. Total RNA samples (n = 6 per diet per time point) were individually hybridised tot the Affymatrix mouse genome 430 2.0 array.

Project description:Some studies have shown that acute intake of high-phenol virgin olive oil reduces pro-inflammatory, pro-oxidant and pro-thrombotic states, but nowadays still remains unclear if those effects attributed to its phenolic fraction could be exerted at transcriptional level in vivo. Two virgin olive oil-based breakfasts with high (398 ppm) and low (70 ppm) content of phenolic compounds were administered to twenty patients (9 men and 11 women) with metabolic syndrome following a double-blinded random crossover design. Prior to the first breakfast intervention, participants followed a 6-week washout period in which they were instructed to not take vitamins, soy supplements, or any drug. To eliminate the potential effect that might exist in their usual dietary habits, all subjects followed a low-fat, carbohydrate rich (CHO) diet during this period and untill the end of the study. In the 24 h before each breakfast intervention, participants were instructed to avoid consuming phenol-rich foods such as fruit or juices, wine, grape juice, chocolate, coffee, tea, olive oil, or soya, and to refrain from intense physical exercise during that period. After a 12 h fasting and following a randomized sequential crossover design with one-week washout period, participants reported to the hospital and received two fat meals consisting of 60 g of white bread, 40 mL of VOO (CANOLIVA®, Antonio Cano e Hijos™, Córdoba, Spain) with high (398 ppm) or low (70 ppm) content in phenolic compounds, and 60,000 IU of vitamin A per m2 of body surface. Olive oil with low content in phenolic compounds was obtained as a result of extraction by physical procedures of most of the phenolic compounds in the high-phenol olive oil, so that both oils kept a similar composition of the remaining macro- and micronutrients. Throughout the 4-h duration of the study, the subjects performed no physical activity, nor did they consume anything but water. Gene expression was performed on peripheral blood mononuclear cells (PBMCs) at postprandial period (4 hours after breakfast) by microarray analysis and verified by qRT-PCR.

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NHLBI TOPMed: Genetics of Lipid Lowering Drugs and Diet Network (GOLDN)

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