Low-fat High-complex Carbohydrate Research Articles

Insulin resistance determines a differential response to changes in dietary fat modification on metabolic syndrome risk factors: the LIPGENE study

Previous data support the benefits of reducing dietary saturated fatty acids (SFAs) on insulin resistance (IR) and other metabolic risk factors. However, whether the IR status of those suffering from metabolic syndrome (MetS) affects this response is not established. Our objective was to determine whether the degree of IR influences the effect of substituting high-saturated fatty acid (HSFA) diets by isoenergetic alterations in the quality and quantity of dietary fat on MetS risk factors. In this single-blind, parallel, controlled, dietary intervention study, MetS subjects (n = 472) from 8 European countries classified by different IR levels according to homeostasis model assessment of insulin resistance (HOMA-IR) were randomly assigned to 4 diets: an HSFA diet; a high-monounsaturated fatty acid (HMUFA) diet; a low-fat, high-complex carbohydrate (LFHCC) diet supplemented with long-chain n-3 polyunsaturated fatty acids (1.2 g/d); or an LFHCC diet supplemented with placebo for 12 wk (control). Anthropometric, lipid, inflammatory, and IR markers were determined. Insulin-resistant MetS subjects with the highest HOMA-IR improved IR, with reduced insulin and HOMA-IR concentrations after consumption of the HMUFA and LFHCC n-3 diets (P < 0.05). In contrast, subjects with lower HOMA-IR showed reduced body mass index and waist circumference after consumption of the LFHCC control and LFHCC n-3 diets and increased HDL cholesterol concentrations after consumption of the HMUFA and HSFA diets (P < 0.05). MetS subjects with a low to medium HOMA-IR exhibited reduced blood pressure, triglyceride, and LDL cholesterol levels after the LFHCC n-3 diet and increased apolipoprotein A-I concentrations after consumption of the HMUFA and HSFA diets (all P < 0.05). Insulin-resistant MetS subjects with more metabolic complications responded differently to dietary fat modification, being more susceptible to a health effect from the substitution of SFAs in the HMUFA and LFHCC n-3 diets. Conversely, MetS subjects without IR may be more sensitive to the detrimental effects of HSFA intake. The metabolic phenotype of subjects clearly determines response to the quantity and quality of dietary fat on MetS risk factors, which suggests that targeted and personalized dietary therapies may be of value for its different metabolic features. This study was registered at clinicaltrials.gov as NCT00429195.

Effect of dietary fat modification on subcutaneous white adipose tissue insulin sensitivity in patients with metabolic syndrome.

To determine whether the insulin resistance that exists in metabolic syndrome (MetS) patients is modulated by dietary fat composition. Seventy-five patients were randomly assigned to one of four diets for 12 wk: high-saturated fatty acids (HSFAs), high-MUFA (HMUFA), and two low-fat, high-complex carbohydrate (LFHCC) diets supplemented with long-chain n-3 (LFHCC n-3) PUFA or placebo. At the end of intervention, the LFHCC n-3 diet reduced plasma insulin, homeostasis model assessment of insulin resistance, and nonsterified fatty acid concentration (p < 0.05) as compared to baseline Spanish habitual (BSH) diet. Subcutaneous white adipose tissue (WAT) analysis revealed decreased EH-domain containing-2 mRNA levels and increased cbl-associated protein gene expression with the LFHCC n-3 compared to HSFA and HMUFA diets, respectively (p < 0.05). Moreover, the LFHCC n-3 decreased gene expression of glyceraldehyde-3-phosphate dehydrogenase with respect to HMUFA and BSH diets (p < 0.05). Finally, proteomic characterization of subcutaneous WAT identified three proteins of glucose metabolism downregulated by the LFHCC n-3 diet, including annexin A2. RT-PCR analysis confirmed the decrease of annexin A2 (p = 0.027) after this diet. Our data suggest that the LFHCC n-3 diet reduces systemic insulin resistance and improves insulin signaling in subcutaneous WAT of MetS patients compared to HSFA and BSH diets consumption.

Obesity and body fat classification in the metabolic syndrome: Impact on cardiometabolic risk metabotype

Obesity is a key factor in the development of the metabolic syndrome (MetS), which is associated with increased cardiometabolic risk. We investigated whether obesity classification by BMI and body fat percentage (BF%) influences cardiometabolic profile and dietary responsiveness in 486 MetS subjects (LIPGENE dietary intervention study). Anthropometric measures, markers of inflammation and glucose metabolism, lipid profiles, adhesion molecules, and hemostatic factors were determined at baseline and after 12 weeks of four dietary interventions (high saturated fat (SFA), high monounsaturated fat (MUFA), and two low fat high complex carbohydrate (LFHCC) diets, one supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs)). About 39 and 87% of subjects classified as normal and overweight by BMI were obese according to their BF%. Individuals classified as obese by BMI (≥ 30 kg/m(2)) and BF% (≥ 25% (men) and ≥ 35% (women)) (OO, n = 284) had larger waist and hip measurements, higher BMI and were heavier (P < 0.001) than those classified as nonobese by BMI but obese by BF% (NOO, n = 92). OO individuals displayed a more proinflammatory (higher C reactive protein (CRP) and leptin), prothrombotic (higher plasminogen activator inhibitor-1 (PAI-1)), proatherogenic (higher leptin/adiponectin ratio) and more insulin resistant (higher HOMA-IR) metabolic profile relative to the NOO group (P < 0.001). Interestingly, tumor necrosis factor-α (TNF-α) concentrations were lower post-intervention in NOO individuals compared with OO subjects (P < 0.001). In conclusion, assessing BF% and BMI as part of a metabotype may help to identify individuals at greater cardiometabolic risk than BMI alone.

Dietary fat modifies the postprandial inflammatory state in subjects with metabolic syndrome: the LIPGENE study

Our aim was to investigate whether the inflammatory state associated to metabolic syndrome (MetS) patients is affected by diets with different fat quality and quantity. Seventy-five subjects from LIPGENE cohort were included in this feeding trial and randomly assigned to one of four diets: high saturated fatty acids (HSFA); high monounsaturated fatty acids (HMUFA) and two low-fat, high complex carbohydrate (LFHCC) diets, supplemented with long-chain n-3 polyunsaturated fatty acids (LFHCC n-3) or placebo (LFHCC), for 12 weeks each. A postprandial fat challenge, reflecting the intervention dietary fat composition, was conducted post-intervention. The HMUFA diet significantly reduced postprandial nuclear transcription factor-kappaB (NF-kB) activity and the nuclear p65 protein levels relative to fasting values (p < 0.05). Furthermore, we observed a postprandial decrease in this protein with the HMUFA diet compared with the HSFA and LFHCC diets (p < 0.05). The postprandial response of inhibitory molecule from NF-kB mRNA levels increased with the HMUFA diet compared with the HSFA and LFHCC n-3 diets (p < 0.05). Postprandial tumor necrosis factor-α and Metalloproteinase 9 mRNA levels were also reduced after the HMUFA diet compared with the HSFA diet (p < 0.05). Our results indicate that the long-term consumption of a healthy diet model with HMUFA attenuates the postprandial inflammatory state associated with MetS.

Adipose triglyceride lipase and hormone-sensitive lipase protein expression in subcutaneous adipose tissue is decreased after an isoenergetic low-fat high-complex carbohydrate diet in the metabolic syndrome

The objective was to determine the contribution of dietary fat quantity and composition to lipolysis and lipolytic gene expression in humans in relation to obesity, insulin resistance, and the metabolic syndrome (MetS). Men and women with the MetS were randomly assigned to one of four isoenergetic diets: a high-fat saturated fat diet (n=10), a high-fat monounsaturated fat diet (n=7), and two low-fat high-complex carbohydrate (LFHCC) diets, one supplemented with 1.24g/day long-chain n-3 PUFA (LFHCC: n=7, LFHCCn-3: n=8). Subcutaneous adipose tissue biopsies were taken before and after the 12-week dietary intervention period. ATGL and HSL mRNA and protein expression was determined. Whole body rate of appearance of free fatty acids (RaFFA) was determined by intravenous infusion of [2H2]-palmitate in a subgroup of men (n=20). Adipose tissue ATGL and HSL mRNA and protein expression was not affected by alterations in dietary fat composition. Pooled analysis comparing the low- and high-fat diets showed that ATGL and HSL protein expression was significantly reduced after the LFHCC diets (P=.04), irrespective of long-chain n-3 PUFA. Moreover, LFHCC diets lowered fasting insulin, HOMAIR, and (LDL)-cholesterol concentrations (P≤.05). Changes in ATGL and HSL protein expression was positively associated with changes in whole body RaFFA (P<.03). The low-fat high-complex carbohydrate diets reduced ATGL and HSL protein expression and significantly improved circulating lipids and insulin sensitivity. Under isoenergetic conditions, dietary fat quantity, rather than composition, may be most important for modulating subcutaneous adipose tissue ATGL and HSL protein expression.

The Effect of Sugar-Sweetened Beverage Intake on Energy Intake in an ad libitum 6-Month Low-Fat High-Carbohydrate Diet

Background/Aims: The increased incidence of obesity coincides with an increased consumption of sugar-sweetened beverages (SSBs). This study investigated the effect of SSB intake on energy intake in an ad libitum 6-month low-fat high-carbohydrate diet in a reanalysis of the CARMEN data. Methods: Forty-seven overweight-to-obese men and women participated in the Maastricht centre of the randomized controlled CARMEN study. They were allocatedto a control (habitual) diet group (CD), a low-fat (–10 energy percent, En%) high simple carbohydrate (SCHO) or low-fat high complex carbohydrate group (CCHO) (SCHO vs. CCHO: 1.5 vs. 0.5) using a controlled laboratory shop system. Reanalyses were made for the energy, amount and density of all drinks and in particular of sweetened beverages (SBs). The SCHO and CD group could select nondiet SBs, including soft drinks and fruit juices, while the CCHO group received SB alternatives. Results: Energy intake decreased in the CCHO and SCHO groups versus the CD group (–2.7 ± 0.4 MJ/day CCHO group vs. –0.2 ± 0.5 MJ/day CD group, p < 0.01; –1.4 ± 0.4 MJ/day SCHO group, not significant). Simple carbohydrate intake increased significantly in the SCHO group versus the CCHO and CD groups (+10.8 ± 1.6 vs. –2.0 ± 0.9 and –0.5 ± 1.1 En%; p < 0.001). In the SCHO and CD groups, energy intake from SBs increased significantly (+187 ± 114 and +101 ± 83 kJ/day, respectively; –432 ± 72 kJ/day in the CCHO group; p < 0.001). Conclusion: Simple carbohydrate intake increased through enhanced intake of nondiet SBs in the SCHO group. Fat reduction combined with only diet SBs in an ad libitum situation has a greater impact on energy intake than fat reduction combined with nondiet SBs.

Effects of dietary fat modification on insulin sensitivity and on other risk factors of the metabolic syndrome—LIPGENE: a European randomized dietary intervention study

Excessive energy intake and obesity lead to the metabolic syndrome (MetS). Dietary saturated fatty acids (SFAs) may be particularly detrimental on insulin sensitivity (SI) and on other components of the MetS. This study determined the relative efficacy of reducing dietary SFA, by isoenergetic alteration of the quality and quantity of dietary fat, on risk factors associated with MetS. A free-living, single-blinded dietary intervention study. MetS subjects (n = 417) from eight European countries completed the randomized dietary intervention study with four isoenergetic diets distinct in fat quantity and quality: high-SFA; high-monounsaturated fatty acids and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with long chain n-3 polyunsaturated fatty acids (LC n-3 PUFAs) (1.2 g per day) or placebo for 12 weeks. SI estimated from an intravenous glucose tolerance test (IVGTT) was the primary outcome measure. Lipid and inflammatory markers associated with MetS were also determined. In weight-stable subjects, reducing dietary SFA intake had no effect on SI, total and low-density lipoprotein cholesterol concentration, inflammation or blood pressure in the entire cohort. The LFHCC n-3 PUFA diet reduced plasma triacylglycerol (TAG) and non-esterified fatty acid concentrations (P < 0.01), particularly in men. There was no effect of reducing SFA on SI in weight-stable obese MetS subjects. LC n-3 PUFA supplementation, in association with a low-fat diet, improved TAG-related MetS risk profiles.

Effects of dietary fat modification on oxidative stress and inflammatory markers in the LIPGENE study

Subjects with the metabolic syndrome (MetS) have enhanced oxidative stress and inflammation. Dietary fat quality has been proposed to be implicated in these conditions. We investigated the impact of four diets distinct in fat quantity and quality on 8-iso-PGF2α (a major F2-isoprostane and oxidative stress indicator), 15-keto-13,14-dihydro-PGF2α (15-keto-dihydro-PGF2α, a major PGF2α metabolite and marker of cyclooxygenase-mediated inflammation) and C-reactive protein (CRP). In a 12-week parallel multicentre dietary intervention study (LIPGENE), 417 volunteers with the MetS were randomly assigned to one of the four diets: two high-fat diets (38% energy (%E)) rich in SFA or MUFA and two low-fat high-complex carbohydrate diets (28%E) with (LFHCC n-3) or without (LFHCC) 1·24g/d of very long chain n-3 fatty acid supplementation. Urinary levels of 8-iso-PGF2α and 15-keto-dihydro-PGF2α were determined by RIA and adjusted for urinary creatinine levels. Serum concentration of CRP was measured by ELISA. Neither concentrations of 8-iso-PGF2α and 15-keto-dihydro-PGF2α nor those of CRP differed between diet groups at baseline (P>0·07) or at the end of the study (P>0·44). Also, no differences in changes of the markers were observed between the diet groups (8-iso-PGF2α, P=0·83; 15-keto-dihydro-PGF2α, P=0·45; and CRP, P=0·97). In conclusion, a 12-week dietary fat modification did not affect the investigated markers of oxidative stress and inflammation among subjects with the MetS in the LIPGENE study.

Effects of dietary fat modification on skeletal muscle fatty acid handling in the metabolic syndrome

In the metabolic syndrome (MetS), increased fat storage in 'nonadipose' tissues such as skeletal muscle may be related to insulin resistance ('lipid overflow' hypothesis). The objective of this study was to examine the effects of dietary fat modification on the capacity of skeletal muscle to handle dietary and endogenous fatty acids (FAs). In total, 29 men with the MetS were randomly assigned to one of four diets for 12 weeks: a high-fat saturated fat diet (HSFA, n=6), a high-fat monounsaturated fat diet (HMUFA, n=7) and two low-fat high-complex carbohydrate diets supplemented with (LFHCCn-3, n=8) or without (LFHCC, n=8) 1.24 g per day docosahexaenoic and eicosapentaenoic acid. Fasting and postprandial skeletal muscle FA handling was examined by measuring arteriovenous concentration differences across the forearm muscle. [(2)H(2)]-palmitate was infused intravenously to label endogenous triacylglycerol (TAG) and free fatty acids in the circulation and subjects received a high-fat mixed meal (2.6 MJ, 61 energy% fat) containing [U-(13)C]-palmitate to label chylomicron-TAG. Postprandial circulating TAG concentrations were significantly lower after dietary intervention in the LFHCCn-3 group compared to the HSFA group (DeltaiAUC -139+/-67 vs 167+/-70 micromol l(-1) min(-1), P=0.009), together with decreased concentrations of [U-(13)C]-labeled TAG, representing dietary FA. Fasting TAG clearance across forearm muscle was decreased on the HSFA diet, whereas no differences were observed in postprandial forearm muscle FA handling between diets. Chronic manipulation of dietary fat quantity and quality did not affect forearm muscle FA handling in men with the MetS. Postprandial TAG concentrations decreased on the LFHCCn-3 diet, which could be (partly) explained by lower concentration of dietary FA in the circulation.

Lipoprotein profile, plasma Ischemia Modified Albumin and LDL density change in the course of postprandial lipemia. Insights from the LIPGENE study

Postprandial lipemia is associated with elevated risk of cardiovascular disease. Very little data exists regarding postprandial response in subjects with metabolic syndrome (MetS). The current study was conducted within the LIPGENE EU Integrated Project. Patients were randomized to one of the four isocaloric fatty meals (Oral Fat Tolerance Tests, OFTT): (A) high-fat, saturated fatty acid (SFA)-rich (HFSA), (B) high-fat, monounsaturated fatty acid (MUFA)-rich (HFMUFA), (C) low-fat, high-complex carbohydrate with 1.24 g high oleic sunflower oil supplement (LFHCC) and (D) low-fat high-complex carbohydrate with 1.24 g long chain n-3 poly-unsaturated fatty acid (LC n-3 PUFA) supplement (LFHCCn-3). The total and incremental areas under the curve (tAUC and iAUC) of plasma lipid and lipoprotein, Ischemia Modified Albumin (IMA) and LDL density were examined in patients with MetS to define effect of OFTT. All types of OFTT transiently increased plasma triglyceride and LDL density (LDLdens). It was paralleled by temporal decrease in total cholesterol (TC), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C). This last effect was partly alleviated in LFHCCn-3 test. A reversible increase of IMA was statistically significant only in the course of HSFA and HMUFA tests. EPA and DHA supplement in combined high complex-carbohydrate meal may attenuate adverse effect of tested meal on LDL particle profile and plasma ischemia modified albumin. No expected associations between measures of central adiposity (waist, WHR), adipose tissue insulin resistance (Adipo-IR), and postprandial responses of TG, TC, LDL-C, HDL-C, LDLdens and IMA/Alb ratio were found in subgroup analysis.Trial registration: ClinicalTrials.gov identifier: NCT00429195.

Dietary fat differentially influences regulatory endothelial function during the postprandial state in patients with metabolic syndrome: From the LIPGENE study

Objective To investigate whether endothelium-dependent vasomotor function and plasma levels of cellular adhesion molecules are affected by diets with different fat quantity and quality during the postprandial state in subjects with the metabolic syndrome (MetS). Methods Patients were randomly assigned to one of four isoenergetic diets distinct in fat quantity and quality: high-SFA (HSFA); high-MUFA (HMUFA) and two low-fat, high-complex carbohydrate (LFHCC) diets, supplemented with 1.24 g/day of long chain n-3 PUFA (LC n-3 PUFA) or placebo for 12 weeks each. Flow-associated vasodilatation of the brachial artery and postprandial plasma levels of total nitrites, nitric oxide (NO) synthase, soluble intercellular cell adhesion molecule-1 (sICAM-1), soluble vascular cell adhesion molecule-1 (sVCAM-1), and P-selectin were assessed post-intervention. Results Post-intervention postprandial flow-associated vasodilatation was significantly higher after the HMUFA diet ( P < 0.05) compared to subjects adhering to the other three diets. Consistently, the postprandial NO synthase response significantly increased during the HMUFA compared with the HSFA and LFHCC (placebo) diets. Postprandial sICAM-1 levels were lower during the HMUFA than during the HSFA and LFHCC n-3 diets. Conclusions Our data support the notion that the HMUFA diet improves postprandial endothelial cell function and decreases postprandial plasma sICAM-1 concentrations in patients with the MetS. These findings suggest that the postprandial state is important for understanding possible cardio-protective effects associated with the Mediterranean diet particularly in subject with the MetS.