High Polyunsaturated Fat Diet Research Articles

A Randomized Trial with Two Hypocaloric Diets with Different Lipid Profiles and Effects on Serum Omentin-1 Levels in Obese Subjects

Background The effects of weight loss therapies on omentin-1 levels have been unclear, showing both elevations and decreases in circulating levels. The role of dietary fat might have an important role. The aim of our investigation was to evaluate the influence of weight decrease on omentin-1 levels after two different high-fat hypocaloric diets. Methods 319 Caucasian obese subjects were randomly allocated during 12 weeks (Diet M (high monounsaturated fat diet) vs. Diet P (high polyunsaturated fat diet)). The mean age was 47.2 ± 5.0 years (range: 26-64), and the mean body mass index (BMI) was 37.9 ± 4.1 kg/m2 (range: 30.6-39.8). Sex distribution was 237 females (74.7%) and 72 males (25.3%). Anthropometric and biochemical parameters were evaluated at basal and after both diets. SPSS 23.0 has been used to realize univariant and multivariant statistical analysis. Results After both diets, BMI, weight, fat mass, waist circumference, systolic blood, LDL-cholesterol, insulin levels, and HOMA-IR decreased in a statistical way from basal values. These improvements were similar in both diets. After Diet P, omentin-1 levels increase (21.2 ± 9.1 ng/ml: P = 0.02), and after Diet M, this adipokine increases (47.1 ± 11.2 ng/ml: P = 0.02), too. The increase of omentin-1 with Diet M was statistically significantly higher than that after Diet P (P = 0.01). A multiple regression analyses adjusted by age and sex reported a statistical relation between BMI (kg/m2) and insulin (UI/L) with omentin-1 levels. Conclusions Our study demonstrated a significant improvement on serum omentin-1 levels after weight loss secondary to both diets; in contrast, omentin-1 improvement was higher with Diet M than with Diet P.

Effects of Three-Month Administration of High-Saturated Fat Diet and High-Polyunsaturated Fat Diets with Different Linoleic Acid (LA, C18:2n-6) to α-Linolenic Acid (ALA, C18:3n-3) Ratio on the Mouse Liver Proteome.

The aim of the study was to evaluate the effect of different types of high-fat diets (HFDs) on the proteomic profile of mouse liver. The analysis included four dietary groups of mice fed a standard diet (STD group), a high-fat diet rich in SFAs (SFA group), and high-fat diets dominated by PUFAs with linoleic acid (LA, C18:2n–6) to α-linolenic acid (ALA, C18:3n–3) ratios of 14:1 (14:1 group) and 5:1 (5:1 group). After three months of diets, liver proteins were resolved by two-dimensional gel electrophoresis (2DE) using 17 cm non-linear 3–10 pH gradient strips. Protein spots with different expression were identified by MALDI-TOF/TOF. The expression of 13 liver proteins was changed in the SFA group compared to the STD group (↓: ALB, APOA1, IVD, MAT1A, OAT and PHB; ↑: ALDH1L1, UniProtKB—Q91V76, GALK1, GPD1, HMGCS2, KHK and TKFC). Eleven proteins with altered expression were recorded in the 14:1 group compared to the SFA group (↓: ARG1, FTL1, GPD1, HGD, HMGCS2 and MAT1A; ↑: APOA1, CA3, GLO1, HDHD3 and IVD). The expression of 11 proteins was altered in the 5:1 group compared to the SFA group (↓: ATP5F1B, FTL1, GALK1, HGD, HSPA9, HSPD1, PC and TKFC; ↑: ACAT2, CA3 and GSTP1). High-PUFA diets significantly affected the expression of proteins involved in, e.g., carbohydrate metabolism, and had varying effects on plasma total cholesterol and glucose levels. The outcomes of this study revealed crucial liver proteins affected by different high-fat diets.

Hunger and satiety responses to high-fat meals after a high-polyunsaturated fat diet: A randomized trial.

Previous studies have shown that polyunsaturated fats (PUFAs) elicit a greater response in satiety after a single-meal challenge compared with other types of fats. The long-term effects of PUFAs on satiety, however, remain unknown. The aim of this study was to determine subjective and physiological hunger and satiety responses to high-fat (HF) meals before and after a 7-d PUFA-rich diet. Twenty-six, healthy weight (body mass index 18-24.9kg/m2), sedentary adults were randomly assigned to either a 7-d PUFA-rich diet (n=8 men and n=8 women) or a 7-d control diet (n=5 men and n=5 women). After a 3-d lead-in diet, participants reported for the baseline visit where anthropometrics, fasting visual analog scale (VAS) measurements, and a fasting blood sample were collected. Then, two HF meals (breakfast and lunch) were consumed. Postprandial blood draws and VAS measures were collected approximately every 30min for 4h after each meal, for a total of 8h. From pre- to post-PUFA-rich diet, there was a decrease in fasting ghrelin (P<0.05) and an increase in fasting peptide YY (PYY; P<0.05); however, there were no changes in fasting insulin or leptin concentrations. The postprandial response for PYY was higher after the PUFA-rich diet visit compared to baseline (P<0.01). However, there were no differences in the postprandial response for ghrelin, insulin, leptin, or VAS measures from pre- to post-diet in either the PUFA-rich diet or control (ns). A PUFA-rich diet consumed for 7d favorably altered fasting and postprandial physiological markers of hunger and satiety; yet, did not alter subjective ratings of hunger or fullness.

Distinct metabolic effects of resveratrol on lipogenesis markers in mice adipose tissue treated with high-polyunsaturated fat and high-protein diets

ObjectiveA healthy diet is essential for the prevention of metabolic syndrome. The present study evaluated the effect of resveratrol associated with high-polyunsaturated fat and high-protein diets on expression of adipogenic and lipogenic genes. Research methods & proceduresFVB/N mice were divided into 6 groups (n=7 each) and fed with experimental diets for 60days: standard (ST), high-fat diet (HFD), and high-protein diet (HPD), with and without resveratrol (RSV) (4g/kg diet). The body weight, food intake, energy intake (kcal), and blood parameters (HDL-C, total cholesterol, glucose, and triglyceride levels) were assessed. Real-time PCR was performed to analyze the expression of adipogenesis and lipogenesis markers: PPARγ, SREBP-1c, ACC and FAS in samples from perigonadal adipose tissue. ResultsIn the HPD+RSV group, resveratrol decreased body weight, body adiposity, adipose tissue weight, adipocyte area, total cholesterol, ACC and FAS expression, and increased HDL-cholesterol in comparison to HPD. In the HPD group there was a decrease in adipocyte area, as well as PPARγ, SREBP-1c and ACC expression in comparison to ST. While in HFD+RSV, resveratrol decreased levels of total cholesterol in comparison to HFD. In the HFD group there was decrease in body weight, and PPARγ, SREBP-1c and ACC expression in comparison to ST. ConclusionsThe obtained results show that resveratrol decreases lipogenesis markers and metabolic parameters in the setting of a high-protein diet. Moreover, resveratrol decreased total cholesterol in both diets. These results point to the increased potential of resveratrol use in prevention of metabolic syndrome, acting on different dietary compositions.

Chronic‐Binge Alcohol‐Induced Hepatic Injury and Inflammation Were Ameliorated in Mice Deficient for Transient Receptor Potential Vanilloid 1 Gene

IntroductionExperimental alcohol‐induced liver injury is exacerbated by a high polyunsaturated fat diet rich in linoleic acid (LA). The aim of the study was to evaluate the role of bioactive oxidized LA metabolites (OXLAMs) and their signaling through the Transient Receptor Potential Vanilloid 1 (TRPV1) in an experimental animal model of alcoholic liver disease (ALD).MethodsC57BL/6 wild type (WT) and Trpv1 knock out mice were fed a diet containing 5% ethanol for 10 days, followed by a single ethanol gavage. Liver steatosis, injury and inflammation were assessed. In vitro studies using HepG2 cells were performed to evaluate OXLAM/TRPV1 signaling.ResultsChronic‐binge alcohol administration to WT animals resulted in a marked increase in plasma OXLAM levels, specifically 9‐ and 13‐HODEs, in parallel with the up‐regulation of hepatic Trpv1. These effects were associated with hepatic steatosis, inflammation and injury. Genetic depletion of Trpv1 did not blunt hepatic steatosis caused by EtOH, but ameliorated hepatic injury and prevented the increase in pro‐inflammatory cytokine and chemokine expression, including Tnf‐α, IL‐6, Mip‐2, Mcp1, and Pai‐1. Exposure of HepG2 cells to 9‐ and 13‐HODEs resulted in activation of TRPV1 signal transduction with the increased intracellular Ca2+ levels, suggesting that OXLAM/TRPV1/Ca2+ signaling may be a relevant pathway contributing to ALD.ConclusionsTRPV1‐OXLAM interactions appear to play a significant role in ethanol‐induced hepatic inflammation/injury, further supporting an important role for dietary lipids in ALD.

The role of visceral and subcutaneous adipose tissue fatty acid composition in liver pathophysiology associated with NAFLD

Visceral adiposity is associated with type-2-diabetes, inflammation, dyslipidemia and non-alcoholic fatty liver disease (NAFLD), whereas subcutaneous adiposity is not. We hypothesized that the link between visceral adiposity and liver pathophysiology involves inherent or diet-derived differences between visceral and subcutaneous adipose tissue to store and mobilize saturated fatty acids. The goal of the present study was to characterize the fatty acid composition of adipose tissue triglyceride and portal vein fatty acids in relation to indices of liver dysregulation. For 8 weeks rats had free access to control (CON; 12.9% corn/safflower oil; 3.6 Kcal/g), high saturated fat (SAT; 45.2% cocoa butter; 4.5 Kcal/g) or high polyunsaturated fat (PUFA; 45.2% safflower oil; 4.5 Kcal/g) diets. Outcome measures included glucose tolerance, visceral and subcutaneous adipose tissue triglyceride, liver phospholipids and plasma (portal and systemic) free fatty acid composition, indices of inflammation and endoplasmic reticulum stress in the liver and adipose tissue depots and circulating adipo/cytokines. Hepatic triglycerides were significantly increased in both high fat diet groups compared to control and were significantly higher in PUFA compared to SAT. Although glucose tolerance was not different among diet groups, SAT increased markers of inflammation and ER stress in the liver and both adipose tissue depots. Fatty acid composition did not differ among adipose depots or portal blood in any dietary group. Overall, these data suggest that diets enriched in saturated fatty acids are associated with liver inflammation, ER stress and injury, but that any link between visceral adipose tissue and these liver indices does not involve selective changes to fatty acid composition in this depot or the portal vein.

Transient Receptor Potential Vanilloid 1 Gene Deficiency Ameliorates Hepatic Injury in a Mouse Model of Chronic Binge Alcohol-Induced Alcoholic Liver Disease

Experimental alcohol-induced liver injury is exacerbated by a high polyunsaturated fat diet rich in linoleic acid. We postulated that bioactive oxidized linoleic acid metabolites (OXLAMs) play a critical role in the development/progression of alcohol-mediated hepatic inflammation and injury. OXLAMs are endogenous ligands for transient receptor potential vanilloid 1 (TRPV1). Herein, we evaluated the role of signaling through TRPV1 in an experimental animal model of alcoholic liver disease (ALD). Chronic binge alcohol administration increased plasma OXLAM levels, specifically 9- and 13-hydroxy-octadecadienoic acids. This effect was associated with up-regulation of hepatic TRPV1. Exposure of hepatocytes to these OXLAMs invitro resulted in activation of TRPV1 signal transduction with increased intracellular Ca(2+) levels. Genetic depletion of TRPV1 did not blunt hepatic steatosis caused by ethanol, but prevented hepatic injury. TRPV1 deficiency protected from hepatocyte death and prevented the increase in proinflammatory cytokine and chemokine expression, including tumor necrosis factor-α, IL-6, macrophage inflammatory protein-2, and monocyte chemotactic protein 1. TRPV1 depletion markedly blunted ethanol-mediated induction of plasminogen activator inhibitor-1, an important alcohol-induced hepatic inflammation mediator, via fibrin accumulation. This study indicates, for the first time, that TRPV1 receptor pathway may be involved in hepatic inflammatory response in an experimental animal model of ALD. TRPV1-OXLAM interactions appear to play a significant role in hepatic inflammation/injury, further supporting an important role for dietary lipids in ALD.

Effect of Lys656Asn Polymorphism of Leptin Receptor Gene on Cardiovascular Risk Factors and Serum Adipokine Levels after a High Polyunsaturated Fat Diet in Obese Patients.

Human obesity is characterized by high levels of leptin, and leptin levels may change with weight loss and dietary restriction. The aim of our study was to investigate the influence of Lys656Asn polymorphism in the leptin receptor gene on cardiovascular risk factors, weight loss, and serum leptin levels to a high polyunsaturated fatty acid (PUFA) hypocaloric diet in obese patients. A sample of 132 obese patients was analyzed in a prospective way with a dietary intervention. The enriched PUFAs hypocaloric intervention consisted in a diet of 1,459 kcal, 45.7% of carbohydrates, 34.4% of lipids, and 19.9% of proteins. In wild-type group, BMI (-1.9 ± 1.4 kg/m(2) ), weight (-4.4 ± 3.2 kg), fat mass (-4.2 ± 3.8 kg), waist circumference (-4.1 ± 3.1 cm), systolic blood pressure (-7.0 ± 12.1 mmHg), diastolic blood pressure (-3.9 ± 6.8 mmHg), insulin (-1.8 ± 5.6 MUI/l) and HOMA-IR (-0.5 ± 1.5 Units) decreased. In mutant genotype group, BMI (-2.0 ± 2.1 kg/m(2) ), weight (-3.6 ± 4.1 kg), waist circumference (-3.1 ± 4.1 cm), total cholesterol (-25.2 ± 19.6 mg/dl), LDL cholesterol (-16.6 ± 25.6 mg/dl), and tryglicerides (-26.6 ± 39.1 mg/dl) decreased. Only leptin levels have a significant decrease in wild genotype group (-6.6 ± 10.2 ng/ml) (25.1%). Carriers of ASn656 allele have a different response than wild-type obese, with a lack of decrease in insulin levels, leptin levels, and HOMA-IR. However, obese patients with this mutant allele have a better lipid profile after weight loss.

The effects of exercise and diet on olfactory capability in detection dogs.

A previous work suggests that dietary fat may influence canine olfaction. The present study evaluated whether olfactory performance could be influenced by forms of dietary fat and exercise. Seventeen certified detection dogs were fed three different diets (high fat, low fat or high polyunsaturated fat) for 12 weeks. After 12 weeks, olfactory testing was performed using a scent wheel in an olfaction laboratory using three explosive materials. The dogs completed eight to twelve scent trials before and after a 30min treadmill exercise on five consecutive days. A mixed-effect logistic regression model was used to examine how diet, pre- or post-exercise, trial number, odourant, mass of target and target position influenced the probability of dogs alerting on the target odour. There were no significant changes in the dog's ability to find a target odour at threshold amounts. Dogs were 1·42 (1·08, 1·87; 95% CI) times as likely to find a target on the high polyunsaturated fat diet relative to the high-fat diet (P=0·009). The low-fat diet was not significantly different from either the high-fat diet or the high polyunsaturated fat diet (P=0·12). Dogs were 1·49 (1·26, 1·76; 95% CI) times as likely to find a target prior to exercise relative to after exercise (P<0·001). Dogs on the high PUFA diet utilising maize oil showed mild improvement in olfaction. The exact reasons are unknown; however, the higher relative amount of linoleic acid in the diet may play a role in olfactory sensation which warrants further examination of optimal diets for detection dogs.

Effects of C358A polymorphism of the endocannabinoid degrading enzyme fatty acid amide hydrolase (FAAH) on weight loss, adipocytokines levels, and insulin resistance after a high polyunsaturated fat diet in obese patients

The C385A polymorphism of FAAH gene (rs324420C>A) has been associated with obesity. We investigate the role of this polymorphism on anthropometric and insulin resistance responses to a high polyunsaturated fat hypocaloric diet. Obese individuals (no.=99) were assessed at baseline and after 3 months of a high polyunsaturated fat hypocaloric diet. Seventy-one patients (71.7%) had the genotype C385C and 28 (28.3%) patients had the C385A (26 patients, 26.3%) or A358A (2 patients, 2.0%) (A allele carriers group) genotype. In A allele carriers and after dietary intervention, total cholesterol (-16.3 ± 37.4 mg/dl) and LDL-cholesterol (-12.9 ± 6.5 mg/dl) levels decreased. In subjects with C385C genotype, the decreases were significant in total cholesterol (-12.3 ± 27.4 mg/dl), LDL-cholesterol (-7.5 ± 20.5 mg/dl), insulin (-2.2 ± 6.2 mUI/l), and homeostasis model assessment of insulin resistance (HOMA-R) (-0.79 ± 1.15 units) levels. The weight loss was similar in both genotype groups (-4.1 ± 3.8 kg vs -4.2 ± 3.2 kg). Only leptin levels had a significant similar decrease in both genotypes. Subjects with C385C genotype of the FAAH showed an improvement on insulin and HOMA-R levels with a high polyunsaturated fat hypocaloric diet after weight loss during 3 months.

Genetic variation in the cannabinoid receptor gene (CNR1) (G1359A polymorphism) and their influence on anthropometric parameters and metabolic parameters under a high monounsaturated vs. high polyunsaturated fat hypocaloric diets

An intragenic polymorphism (1359 G/A) of the cannabinoid receptor 1 (CNR1) gene was reported as a common polymorphism in Caucasian populations (rs1049353). Intervention studies with this polymorphism have yield contradictories results. We decide to investigate the role of polymorphism (G1359A) of (CNR1) gene on metabolic parameters and weight loss secondary to a high monounsaturated fat and high polyunsaturated fat hypocaloric diets in obese subjects. A population of 258 obese subjects was analyzed in a randomized trial. A nutritional evaluation was performed at the beginning and at the end of a 3-month period in which subjects received 1 of 2 diets (diet M: high monounsaturated fat diet vs diet P: high polyunsaturated fat diet). One hundred and sixty five patients (63.9%) had the genotype G1359G and 93 (36.1%) patients (A allele carriers) had G1359A (78 patients,30.3%) or A1359A (15 patients,5.8%) genotypes. In subjects with both genotypes, body mass index, weight, fat mass, waist circumference and systolic blood pressures decreased with both diets. With the diet-type M and in both genotype groups, biochemical parameters remained unchanged. After the diet type P and in subjects with both genotypes, glucose, total cholesterol, low-density lipoprotein (LDL) cholesterol, insulin and homeostasis model assessment for insulin resistance (HOMA-IR) levels decreased. In G1359G genotype subjects after both diets, leptin levels decreased. The finding of this study is the association of the A allele with a lack of improvement on leptin levels. Subjects with both genotypes and after a high polyunsaturated fat hypocaloric diet showed a significant improvement of LDL cholesterol, total cholesterol, HOMA-IR and insulin levels.

Effect of Fatty Acid–Binding Protein 2 Ala54Thr Genotype on Weight Loss and Cardiovascular Risk Factors After a High–Polyunsaturated Fat Diet in Obese Patients

BackgroundIt has been found that the expression of fatty acid-binding protein 2 messenger RNA is under dietary control.The aim of our study was to investigate the influence of Thr54 polymorphism...

Relation of -55CT polymorphism of UCP3 gene with weight loss and metabolic changes after a high polyunsaturated fat diet in obese patients

The alteration in the protein expression of UCP3 could reduce energy consumption and increase energy storage as fat. The aim of our study was to investigate the influence of -55CT polymorphism of UCP3 gene in the metabolic response, weight loss and serum levels of adipokines following a hypocaloric diet rich in polyunsaturated fat in obese patients. A sample of 133 obese patients were analyzed prospectively for 3 months. The hypocaloric diet was 1459 kcal, 45.7% carbohydrate, 34.4% from 19.9% lipids and proteins. The fat distribution was, a 21.8% saturated fat, 55.5% monounsaturated and 22.7% of polyunsaturated fat (7 g per day of fatty acids w6, 2 g per day of w -3 and a ratio w6/w3 of 3.5). A total of 100 patients (28 males/72 females) (75.2%) had genotype - 55CC (wild genotype group) and 33 patients (8 males/25 females) (24.8%) -55CT genotype (group mutant genotype). In the wild genotype, body mass index (-2.5 ± 5.3 kg/m²), weight (-4.2 ± 3.7 kg), fat mass (-3,7 ± 3.3 kg), waist circumference (-4.1 ± 2.9 cm), systolic blood pressure (-4.9 ± 10.1 mmHg), total cholesterol levels (- 16.1 ± 23.6 mg / dl), LDL cholesterol (-11.1 ± 26.8 mg/dl), triglycerides (-12.0 ± 46.8 mg/dl), insulin (-1.8 ± 4.5 IU/L), HOMA-R (-0.6 ± 1.5) and leptin (-6.2 ± 8.4 ng/ml) decreased. In the mutant genotype anthropometric parameters were significantly decreased without significant changes in biochemical parameters. The T allele carriers of -55CT UCP3 polymorphism exhibit no metabolic response to weight loss induced by a hypocaloric diet rich in polyunsaturated fatty acids.

Abstract 17091: High Saturated Fat Intake Improves Survival in Genetic Cardiomyopathy Compared to a High Polyunsaturated Fat Diet or a Low Fat Diet

Surprisingly, a high fat diet comprised mainly of saturated fatty acids improves LV function and survival in rat models of heart failure induced by hypertension or myocardial infarction. The mechanism for this effect is not clear, nor is it known if a similar effect occurs with a high fat diet composed of plant derived polyunsaturated fatty acids (PUFA), or in genetic cardiomyopathies. We determined if survival in cardiomyopathic hamsters (Bio TO-2 strain) is prolonged by a high fat diet compared to a low fat diet (see table). Further, we compared the effect of high fat diets enriched with either saturated fat (palmitate and stearate), or PUFAs from plant sources(primarily linoleic and α-linolenic acids). Cardiomyopathic hamsters (6 wks old) were fed either a Low Fat diet; a High PUFA diet, or a High Saturated Fat diet. Survival was assessed (n=30/group), and subgroups were evaluated at 30 wks of age (n=12/group) for LV and mitochondrial function. The diet has no effect on LV function as assessed by echocardiography, and there was no difference in body weight or LV mass. Since there is impaired mitochondrial function in heart failure and dietary lipid composition might positively impact mitochondrial function, isolated mitochondria were assessed. Respiration and Ca 2+ -induced mitochondrial permeability transition were unaffected by diet. On the other hand, the high PUFA diet increased fat pad mass compared with the two other cardiomyopathic groups and elevated plasma free fatty acid concentration (p&lt;0.05). Importantly, there was a significant increase in survival in the high saturated sat group compared to the either the low fat or the high PUFA groups after 16 months of treatment (p&lt;0.0001). These results show that a high fat diet comprised largely of long chain saturated fatty acids increase survival in cardiomyopathic hamsters compared to either a low fat diet or a high fat diet comprised of PUFA from plant sources. The effect was independent of improved mitochondrial function.

Lipid Fatty Acid Profile Analyses in Liver and Serum in Rats with Nonalcoholic Steatohepatitis Using Improved Gas Chromatography−Mass Spectrometry Methodology

Fatty acids (FAs) are essential components of lipids and exhibit important biological functions. The analyses of FAs are routinely carried out by gas chromatography-mass spectrometry after multistep sample preparation. In this study, several key experimental factors were carefully examined, validated, and optimized to analyze free fatty acid (FFA) and FA profiles of triglycerides and phospholipids in serum or tissue samples. These factors included (1) methylation/transesterification reagents, (2) validation of internal standards, and (3) final step concentration of FA methyl esters. This new method was utilized to analyze FFAs and the FA profiles of triglycerides and phospholipids in the serum and liver from a recently established rat model of nonalcoholic steatohepatitis (NASH). In this model, rats were fed a 220 kcal kg (-3/4) day (-1) diet containing either 5 or 70% corn oil for 21 days using total enteral nutrition. FA compositions of the serum and liver were found to shift from a pattern dominated by saturated and monounsaturated FAs (C16:0/18:1) to one dominated by polyunsaturated C18:2 derived from dietary linoleic acid. Alteration of FA composition in liver after overfeeding of high polyunsaturated fat diets may contribute to the progression of pathological changes from steatosis to inflammation, necrosis, and fibrosis observed in NASH.

Skeletal muscle inflammation is not responsible for the rapid impairment in adiponectin response with high-fat feeding in rats

Adiponectin (Ad) is an insulin-sensitizing adipokine known to stimulate fatty acid (FA) oxidation in skeletal muscle. Skeletal muscle can become resistant to Ad very rapidly, after only 3 days of high saturated fat feeding in rats. Whether the same occurs following a high polyunsaturated fat diet is unknown. Obesity, insulin resistance, and hyperlipidemia are recognized as low-grade inflammatory diseases; therefore, we hypothesized that high-fat feeding induces inflammation, which interferes with Ad action at skeletal muscle. To this end, rats were placed into one of three dietary groups, control (CON, 10% kcal from fat), high saturated (SAT), or high polyunsaturated (PUFA) fat (60% kcal from fat) for 3 days to determine whether Ad resistance develops. Half of the animals from each group were further supplemented with aspirin, a common anti-inflammatory drug. Ad stimulated FA metabolism, Ad signaling intermediates [AdipoR1, APPL1, LKB1, AMPK, and acetyl-CoA carboxylase (ACC)], and inflammatory proteins [Toll-like receptor (TLR4), IKK alpha/beta, IkappaB alpha, NF-kappaB, suppressor of cytokine signaling-3 (SOCS3), and JNK] were measured in soleus muscle. Three days of SAT feeding induced Ad resistance in soleus muscle, assessed as an inability of Ad to phosphorylate ACC and increase FA oxidation. In PUFA-fed animals, Ad-stimulated FA oxidation and ACC phosphorylation to the same degree as CON animals (FA oxidation: +35%, +41%; pACC +29%, +19%; CON, PUFA, P < 0.05). However, neither SAT nor PUFA feeding for 3 days induced skeletal muscle inflammation. Surprisingly, aspirin prevented Ad-stimulated increases in FA oxidation. In conclusion, FA type is critical in the development of Ad resistance, but this does not appear to be mediated by inflammation.

Baseline Serum C-Reactive Protein Is Associated with Lipid Responses to Low-Fat and High-Polyunsaturated Fat Diets

Baseline serum C-reactive protein (CRP) concentrations play a role in the lipid response to diet. This study was a randomized, cross-over, controlled feeding study with 3 phases of 25 d each aimed at determining whether baseline CRP concentrations modulate the serum lipid response to diets differing in fat type and quantity. Participants were adult men and women, age 19–65 y, with LDL-cholesterol concentrations of 3.37–4.66 mmol/L. All participants consumed 3 diets differing in the type of snack, either low or high in fat: low-fat (30.8% of energy), moderate in fat and saturated fat (37.9 and 11.4% of energy, respectively), or moderate in fat and polyunsaturated fat (36.3 and 9.7% of energy, respectively). Using baseline CRP as a continuous variable, CRP × diet interactions on change in serum lipoprotein_a (P = 0.045) and HDL-cholesterol (P = 0.06) were observed. When we used previously established categories to define CRP concentrations (low, <1 mg/L; intermediate, 1–3 mg/L; or high, >3 mg/L), we found a CRP × diet interaction on change in triglyceride concentrations (P = 0.03) and trends for CRP × diet interaction on change in LDL (P = 0.06) and total cholesterol (P = 0.07). If replicated, these results suggest that considering baseline CRP concentrations when prescribing dietary interventions to lower lipid concentrations may be useful. Individuals with high baseline CRP concentrations may benefit from moderate-fat, high polyunsaturated fat diets, whereas those with low baseline CRP concentrations may obtain greater lipid-lowering benefits from low-fat diets.

Genotype–Phenotype Associations: Modulation by Diet and Obesity

Changes in diet are likely to reduce chronic disorders, but after decades of active research and heated discussion, the question still remains: what is the optimal diet to achieve this elusive goal? Is it a low-fat diet, as traditionally recommended by multiple medical societies? Or a high monounsaturated fat (MUFA) diet as predicated by the Mediterranean diet? Perhaps a high polyunsaturated fat (PUFA) diet based on the cholesterol-lowering effects? The right answer may be all of the above but not for everybody. A well-known phenomenon in nutrition research and practice is the dramatic variability in interindividual response to any type of dietary intervention. There are many other factors influencing response, and they include, among many others, age, sex, physical activity, alcohol, and smoking as well as genetic factors that will help to identify vulnerable populations/individuals that will benefit from a variety of more personalized and mechanistic-based dietary recommendations. This potential could and needs to be developed within the context of nutritional genomics that in conjunction with systems biology may provide the tools to achieve the holy grail of dietary prevention and therapy of chronic diseases and cancer. This approach will break with the traditional public health approach of "one size fits all." The current evidence based on nutrigenetics has begun to identify subgroups of individuals who benefit more from a low-fat diet, whereas others appear to benefit more from high MUFA or PUFA diets. The continuous progress in nutrigenomics will allow some time in the future to provide targeted gene-based dietary advice.

A new model for nonalcoholic steatohepatitis in the rat utilizing total enteral nutrition to overfeed a high-polyunsaturated fat diet

We have used total enteral nutrition (TEN) to moderately overfeed rats high-polyunsaturated fat diets to develop a model for nonalcoholic steatohepatitis (NASH). Male Sprague-Dawley rats were fed by TEN a 187 kcal.kg(-3/4).day(-1) diet containing 5% (total calories) corn oil or a 220 kcal.kg(-3/4).day(-1) diet in which corn oil constituted 5, 10, 25, 35, 40, or 70% of total calories for 21 or 65 days. Rats fed the 5% corn oil, 220 kcal.kg(-3/4).day(-1)diet had greater body weight gain (P < or = 0.05), fat mass (P < or = 0.05), and serum leptin and glucose levels (P < or = 0.05), but no liver pathology. A dose-dependent increase in hepatic triglyceride deposition occurred with increase in percent corn oil in the 220 kcal.kg(-3/4).day(-1) groups (P < or = 0.05). Steatosis, macrophage infiltration, apoptosis, and focal necrosis were present in the 70% corn oil group, accompanied by elevated serum alanine aminotransferase (ALT) levels (P < or = 0.05). An increase in oxidative stress (thiobarbituric acid-reactive substances) and TNF-alpha expression (P < or = 0.05) was observed in the 70% corn oil group, as well as an increase in hepatic CYP2E1 and CYP4A1 expression (P < or = 0.05). Significant positive correlations were observed between the level of dietary corn oil and the degree of pathology, ALTs, oxidative stress, and inflammation. Liver pathology was progressive with increased necrosis, accompanied by fibrosis, observed after 65 days of TEN. Increased expression of CD36 and l-fabp mRNA suggested development of steatosis was associated with increased fatty acid transport. These data suggest that intragastric infusion of a high-polyunsaturated fat diet at a caloric level of 17% excess total calories results in pathology similar to clinical NASH.

Flow-Mediated Dilatation Is Impaired by a High–Saturated Fat Diet but Not by a High-Carbohydrate Diet

It is unknown whether a low-fat diet, which may elevate triglycerides and lower high-density lipoprotein (HDL) cholesterol, harms the endothelium. Our aim was to determine whether a low-fat, high-carbohydrate (CARB) diet impaired endothelial vasodilation compared with high saturated fat (SFA), monounsaturated fat (MUFA), or polyunsaturated fat (PUFA) diets. Forty healthy subjects were randomly crossed over to 4, 3-week isocaloric diets high in PUFA, MUFA, or SFA, containing at least 25 g of the relevant fat or a low-fat, CARB, high-glycemic load diet. Flow-mediated dilatation (FMD), fasting blood lipids, high sensitivity C-reactive protein, plasma intercellular, and vascular adhesion molecules plasma E- and P-selectin were measured after each intervention. SFA impaired FMD compared with all other diets (5.41+/-2.45% versus 10.80+/-3.69%; P=0.01). FMD did not change on CARB relative to MUFA or PUFA, despite 23% to 39% rises in triglyceride and 10% to 15% falls in HDL cholesterol. P-selectin was highest after SFA (121+/-52.7 ng/mL) versus MUFA (98+/-44.5 ng/mL; P=0.001) and PUFA (96+/-36.4 ng/mL; P=0.001). High SFA caused deterioration in FMD compared with high PUFA, MUFA, or CARB diets. Inflammatory responses may also be increased on this diet.