Dietary Fat Manipulation Research Articles

The Effect of Dietary Carbohydrate and Fat Manipulation on the Metabolome and Markers of Glucose and Insulin Metabolism: A Randomised Parallel Trial.

High carbohydrate, lower fat (HCLF) diets are recommended to reduce cardiometabolic disease (CMD) but low carbohydrate high fat (LCHF) diets can be just as effective. The effect of LCHF on novel insulin resistance biomarkers and the metabolome has not been fully explored. The aim of this study was to investigate the impact of an ad libitum 8-week LCHF diet compared with a HCLF diet on CMD markers, the metabolome, and insulin resistance markers. n = 16 adults were randomly assigned to either LCHF (n = 8, <50 g CHO p/day) or HCLF diet (n = 8) for 8 weeks. At weeks 0, 4 and 8, participants provided fasted blood samples, measures of body composition, blood pressure and dietary intake. Samples were analysed for markers of cardiometabolic disease and underwent non-targeted metabolomic profiling. Both a LCHF and HCLF diet significantly (p < 0.01) improved fasting insulin, HOMA IR, rQUICKI and leptin/adiponectin ratio (p < 0.05) levels. Metabolomic profiling detected 3489 metabolites with 78 metabolites being differentially regulated, for example, an upregulation in lipid metabolites following the LCHF diet may indicate an increase in lipid transport and oxidation, improving insulin sensitivity. In conclusion, both diets may reduce type 2 diabetes risk albeit, a LCHF diet may enhance insulin sensitivity by increasing lipid oxidation.

A novel maladaptive unfolded protein response as a mechanism for small bowel resection-induced liver injury.

The unfolded protein response (UPR) is a complex adaptive signaling pathway activated by the accumulation of misfolded proteins in the endoplasmic reticulum (ER). ER stress (ERS) triggers a cascade of responses that converge upon C/EBP homologous protein (CHOP) to drive inflammation and apoptosis. Herein, we sought to determine whether liver injury and fibrosis after small bowel resection (SBR) were mediated by a maladaptive hepatic ERS/UPR. C57BL/6 mice underwent 50% proximal SBR or sham operation. Markers of liver injury and UPR/ERS pathways were analyzed. These were compared with experimental groups including dietary fat manipulation, tauroursodeoxycholic acid (TUDCA) treatment, distal SBR, and global CHOP knockout (KO). At 10 wk, proximal SBR had elevated alanine aminotransferase/aspartate aminotransferase (ALT/AST) (P < 0.005) and greater hepatic tumor necrosis factor-α (TNFα) (P = 0.001) and collagen type 1 α1 (COL1A1) (P = 0.02) than shams. SBR livers had increased CHOP and p-eIF2α, but were absent in activating transcription factor 4 (ATF4) protein expression. Low-fat diet (LFD), TUDCA, and distal SBR groups had decreased liver enzymes, inflammation, and fibrosis (P < 0.05). Importantly, they demonstrated reversal of hepatic UPR with diminished CHOP and robust ATF4 signal. CHOP KO-SBR had decreased ALT but not AST compared with wild-type (WT)-SBR (P = 0.01, P = 0.12). There were no differences in TNFα and COL1A1 (P = 0.09, P = 0.50). SBR-induced liver injury, fibrosis is associated with a novel hepatic UPR/ERS response characterized by increased CHOP and decreased ATF4. LFD, TUDCA, and ileocecal resection rescued the hepatic phenotype and reversed the UPR pattern. Global CHOP KO only partially attenuated liver injury. This underscores the significance of disruptions to the gut/liver axis after SBR and potentiates targets to mitigate the progression of intestinal failure-associated liver disease.NEW & NOTEWORTHY The unfolded protein response (UPR) is a complex signaling cascade that converges upon C/EBP-homologous protein (CHOP). Under conditions of chronic cellular stress, the UPR shifts from homeostatic to proapoptotic leading to inflammation and cell death. Here, we provide evidence that small bowel resection-induced liver injury and fibrosis are mediated by a maladaptive hepatic UPR. Low-fat diet, TUDCA treatment, and ileocecal resection rescued the hepatic phenotype and reversed the UPR pattern.

Prenatal High-Fat Diet Rescues Communication Deficits in Fmr1 Mutant Mice in a Sex-Specific Manner

Using high-throughput analysis methods, the present study sought to determine the impact of prenatal high-fat dietary manipulations on isolation-induced ultrasonic vocalization production in both male and female Fmr1mutants on postnatal day 9. Prior to breeding, male FVB/129 Fmr1 wildtype and female Fmr1 heterozygous breeding pairs were assigned to 1 of 3 diet conditions: standard lab chow, omega-3 fatty acid-enriched chow, and a diet controlling for the fat increase. Prenatal exposure to omega-3 fatty acids improved reductions in the number of calls produced by Fmr1heterozygotes females. Moreover, diminished spectral purity in the female Fmr1homozygous mouse was rescued by exposure to both high-fat diets, although these effects were not seen in the male Fmr1knockout. Prenatal dietary fat manipulation also influenced several other aspects of vocalization production, such as the number of calls produced and their fundamental frequency, aside from effects due to loss of Fmr1.Specifically, in males, regardless of genotype, prenatal exposure to high omega-3s increased the average fundamental frequency of calls. These data support the need for future preclinical and clinical work elucidating the full potential of prenatal high-fat diets as a novel therapeutic alternative forFragile X syndrome.

Phenotypic sexual dimorphism in response to dietary fat manipulation in C57BL/6J mice.

Obesity and the metabolic syndrome are increasingly prevalent in society and their complications and response to treatment exhibit sexual dimorphism. Mouse models of high fat diet-induced obesity are commonly used for both mechanistic and therapeutic studies of metabolic disease and diabetes. However, the inclusion of female mammals in obesity research has not been a common practice, and has resulted in a paucity of data regarding the effect of sex on metabolic parameters and its applicability to humans. Here we analyzed male and female C57BL/6 J mice beginning at 4 weeks of age that were placed on a low-fat diet (LFD, 10% calories from fat), a Western Diet (WD, 45% calories from fat), or a high fat diet (HFD, 60% calories from fat). Assessments of body composition, glucose homeostasis, insulin production, and energy metabolism, as well as histological analyses of pancreata were performed. Both male and female C57BL/6 J mice had similar increases in total percent body weight gain with both WD and HFD compared to LFD, however, male mice gained weight earlier upon HFD or WD feeding compared to female mice. Male mice maintained their caloric food intake while reducing their locomotor activity with either WD or HFD compared to LFD, whereas female mice increased their caloric food intake with WD feeding. Locomotor activity of female mice did not significantly change upon WD or HFD feeding, yet female mice exhibited increased energy expenditure compared to WD or HFD fed male mice. Glucose tolerance tests performed at 4, 12 and 20 weeks of dietary intervention revealed impaired glucose tolerance that was worse in male mice compared to females. Furthermore, male mice exhibited an increase in pancreatic β cell area as well as reduced insulin sensitivity after HFD feeding compared to WD or LFD, whereas female mice did not. Male and female C57BL/6 J mice exhibited strikingly different responses in weight, food consumption, locomotor activity, energy expenditure and β cell adaptation upon dietary manipulation, with the latter exhibiting less striking phenotypic changes. We conclude that the nature of these responses emphasizes the need to contextualize studies of obesity pathophysiology and treatment with respect to sex.

Effects of dietary fat manipulation on cognition in mice and rats: protocol for a systematic review and meta-analysis

Introduction and objectiveThe Western diet that comprises high levels of long-chain saturated fats and sugar is associated not only with metabolic disorders such as obesity and type 2 diabetes but...

Dietary fatty acids as nutritional modulators of sirtuins: a systematic review.

The sirtuins (SIRT1 to SIRT7) constitute a family of highly conserved nicotinamide adenine dinucleotide-dependent proteins. When activated, sirtuins control essential cellular processes to maintain metabolic homeostasis, while lack of expression of sirtuins has been related to chronic disease. The aim of this systematic review is to analyze the role of fat consumption as a modulator of human sirtuins. This review was conducted according to PRISMA guidelines. Studies were identified by searches of the electronic databases PubMed/MEDLINE, Scopus, and Web of Science. Randomized clinical trials assessing the effect of fatty acid consumption on sirtuin mRNA expression, sirtuin protein expression, or sirtuin protein activity were eligible for inclusion. Two authors screened and determined the quality of the studies; disagreements were resolved by the third author. All authors compared the compiled data. Seven clinical studies with 3 different types of interventions involving healthy and nonhealthy participants were selected. Only SIRT1 and SIRT3 were evaluated. Overall, the evidence from clinical studies to date is insufficient to understand how lipid consumption modulates sirtuins in humans. The best-characterized mechanism highlights oleic acid as a natural activator of SIRT1. These results draw attention to a new field of interest in nutrition science. The possible activation of sirtuins by dietary fat manipulation may represent an important nutritional strategy for management of chronic and metabolic disease. PROSPERO registration number CRD42018114456.

Impact of the Apolipoprotein E (epsilon) Genotype on Cardiometabolic Risk Markers and Responsiveness to Acute and Chronic Dietary Fat Manipulation

Apolipoprotein (APO) E (ε) genotype is considered to play an important role in lipid responses to dietary fat manipulation but the impact on novel cardiometabolic risk markers is unclear. To address this knowledge gap, we investigated the relationship between the APOE genotype and cardiometabolic risk markers in response to acute and chronic dietary fat intakes. Associations with fasting (baseline) outcome measures (n = 218) were determined using data from the chronic DIVAS (n = 191/195 adults at moderate cardiovascular disease risk) and acute DIVAS-2 (n = 27/32 postmenopausal women) studies examining the effects of diets/meals varying in saturated, polyunsaturated and monounsaturated (MUFA) fatty acid composition. Participants were retrospectively genotyped for APOE (rs429358, rs7412). For baseline cardiometabolic outcomes, E4 carriers had higher fasting total and low-density lipoprotein-cholesterol (LDL-C), total cholesterol: high-density lipoprotein-cholesterol (HDL-C) and LDL-C: HDL-C ratios, but lower C-reactive protein (CRP) than E3/E3 and E2 carriers (p ≤ 0.003). Digital volume pulse stiffness index was higher in E2 carriers than the E3/E3 group (p = 0.011). Following chronic dietary fat intake, the significant diet × genotype interaction was found for fasting triacylglycerol (p = 0.010), with indication of a differential responsiveness to MUFA intake between the E3/E3 and E4 carriers (p = 0.006). Test fat × genotype interactions were observed for the incremental area under the curve for the postprandial apolipoprotein B (apoB; p = 0.022) and digital volume pulse reflection index (DVP-RI; p = 0.030) responses after the MUFA-rich meals, with a reduction in E4 carriers and increase in the E3/E3 group for the apoB response, but an increase in E4 carriers and decrease in the E3/E3 group for the DVP-RI response. In conclusion, baseline associations between the APOE genotype and fasting lipids and CRP confirm previous findings, although a novel interaction with digital volume pulse arterial stiffness was observed in the fasted state and differential postprandial apoB and DVP-RI responses after the MUFA-rich meals. The reported differential impact of the APOE genotype on cardiometabolic markers in the acute and chronic state requires confirmation.

Apolipoprotein E (epsilon) genotype has a greater impact on apoB-48 than apoB-100 responses to dietary fat manipulation-insights from the SATgenε study.

To determine the contribution of intestinally and liver-derived lipoproteins to the postprandial plasma triacylglycerol (TAG) response in APOE3/E3 and E3/E4 individuals following chronic dietary fat manipulation. In sequential order, participants (n = 12 E3/E3, n = 11 E3/E4) followed low fat; high-fat, high-saturated fat (HSF); and HSF with 3.45 g/day docosahexaenoic acid (HSF-DHA) diets, each for 8 weeks. After each dietary period, an acute test meal with a macronutrient profile representative of the dietary intervention was consumed. Apolipoprotein (apo)B isoforms were determined in isolated TAG-rich lipoprotein fractions (Svedberg flotation rate (Sf ) > 400, Sf 60-400, and Sf 20-60) by specific ELISA. A genotype × meal/diet interaction for the Sf > 400 fraction apoB-48 response (p < 0.05) was observed, with higher concentrations reached after the low fat than HSF-DHA meal in E4 carriers. This finding was associated with a lower TAG content of the Sf > 400 particles. Fasting Sf 60-400 and 20-60 apoB-48 concentrations were also significantly higher in E4 carriers. No impact of genotype on the apoB-100 responses was evident. Our study revealed marked effects of dietary fat composition on the Sf > 400 apoB-48 response and particle TAG content in E4 carriers relative to the "wild-type" E3/E3 genotype, which suggest APOE genotype is a potential modulator of chylomicron particle synthesis.

Interaction between BMI and APOE genotype is associated with changes in the plasma long-chain–PUFA response to a fish-oil supplement in healthy participants

Carriers of the apolipoprotein E ɛ4 (APOE4) allele are lower responders to a docosahexaenoic acid (DHA) supplement than are noncarriers. This effect could be exacerbated in overweight individuals because DHA metabolism changes according to body mass index (BMI; in kg/m²). We evaluated the plasma fatty acid (FA) response to a DHA-rich supplement in APOE4 carriers and noncarriers consuming a high-saturated fat diet (HSF diet) and, in addition, evaluated whether being overweight changed this response. This study was part of the SATgenɛ trial. Forty-one APOE4 carriers and 41 noncarriers were prospectively recruited and consumed an HSF diet for 8-wk followed by 8 wk of consumption of an HSF diet with the addition of DHA and eicosapentaenoic acid (EPA) (HSF + DHA diet; 3.45 g DHA/d and 0.5 g EPA/d). Fasting plasma samples were collected at the end of each intervention diet. Plasma total lipids (TLs) were separated into free FAs, neutral lipids (NLs), and phospholipids by using solid-phase extraction, and FA profiles in each lipid class were quantified by using gas chromatography. Because the plasma FA response to the HSF + DHA diet was correlated with BMI in APOE4 carriers but not in noncarriers, the following 2 groups were formed according to the BMI median: low BMI (<25.5) and high BMI (≥25.5). In response to the HSF + DHA diet, there were significant BMI × genotype interactions for changes in plasma concentrations of arachidonic acid and DHA in phospholipids and TLs and of EPA in NLs and TLs (P ≤ 0.05). APOE4 carriers were lower plasma responders to the DHA supplement than were noncarriers but only in the high-BMI group. Our findings indicate that apolipoprotein E genotype and BMI may be important variables that determine the plasma long-chain PUFA response to dietary fat manipulation. APOE4 carriers with BMI ≥25.5 may need higher intakes of DHA for cardiovascular or other health benefits than do noncarriers.

Apolipoprotein E Genotype Has a Modest Impact on the Postprandial Plasma Response to Meals of Varying Fat Composition in Healthy Men in a Randomized Controlled Trial

Background:Apolioprotein E (APOE) genotype is reported to influence a person’s fasting lipid profile and potentially the response to dietary fat manipulation. The impact of APOE genotype on the responsiveness to meals of varying fat composition is unknown. Objective:We examined the effect of meals containing 50 g of fat rich in saturated fatty acids (SFAs), unsaturated fatty acids (UNSATs), or SFAs with fish oil (SFA-FO) on postprandial lipemia. Method:A randomized, controlled, test meal study was performed in men recruited according to the APOE genotype (n = 10 APOE3/3, n = 11 APOE3/E4). Results:For the serum apoE response (meal × genotype interaction P = 0.038), concentrations were on average 8% lower after the UNSAT than the SFA-FO meal in APOE4 carriers (P = 0.015) only. In the genotype groups combined, there was a delay in the time to reach maximum triacylglycerol (TG) concentration (mean ± SEM: 313 ± 25 vs. 266 ± 27 min) and higher maximum nonesterified fatty acid (0.73 ± 0.05 vs. 0.60 ± 0.03 mmol/L) and glucose (7.92 ± 0.22 vs. 7.25 ± 0.22 mmol/L) concentrations after the SFA than the UNSAT meal, respectively (P ≤ 0.05). In the Svedberg flotation rate 60–400 TG-rich lipoprotein fraction, meal × genotype interactions were observed for incremental area under the curve (IAUC) for the TG (P = 0.038) and apoE (P = 0.016) responses with a 58% lower apoE IAUC after the UNSAT than the SFA meal (P = 0.017) in the E4 carriers. Conclusions:Our data indicate that APOE genotype had a modest impact on the postprandial response to meals of varying fat composition in normolipidemic men. The physiologic importance of greater apoE concentrations after the SFA-rich meals in APOE4 carriers may reflect an impact on TG-rich lipoprotein clearance from the circulation. This trial was registered at clinicaltrials.gov as NCT01522482.

Greater impact of dietary fat manipulation than apolipoprotein E genotype on ex vivo cytokine production – Insights from the SATgenε study

Apolipoprotein E (APOE) genotype is believed to play an important role in cardiovascular risk. APOE4 carriers have been associated with higher blood lipid levels and a more pro-inflammatory state compared with APOE3/E3 individuals. Although dietary fat composition has been considered to modulate the inflammatory state in humans, very little is known about how APOE genotype can impact on this response. In a follow-up to the main SATgenε study, we aimed to explore the effects of APOE genotype, as well as, dietary fat manipulation on ex vivo cytokine production. Blood samples were collected from a subset of SATgenε participants (n=52/88), prospectively recruited according to APOE genotype (n=26 E3/E3 and n=26 E3/E4) after low-fat (LF), high saturated fat (HSF) and HSF with 3.45g docosahexaenoic acid (DHA) dietary periods (each diet eight weeks in duration assigned in the same order) for the measurement of ex vivo cytokine production using whole blood culture (WBC). Concentrations of IL-1beta, IL-6, IL-8, IL-10 and TNF-alpha were measured in WBC supernatant samples after stimulation for 24h with either 0.05 or 1μg/ml of bacterial lipopolysaccharide (LPS). Cytokine levels were not influenced by genotype, whereas, dietary fat manipulation had a significant impact on TNF-α and IL-10 production; TNF-α concentration was higher after consumption of the HSF diet compared with baseline and the LF diet (P<0.05), whereas, IL-10 concentration was higher after the LF diet compared with baseline (P<0.05). In conclusion, our study has revealed the amount and type of dietary fat can significantly modulate the production of TNF-α and IL-10 by ex vivo LPS-stimulated WBC samples obtained from normolipidaemic subjects.

OC-058 Bile Acid Malabsorption: “The Unusual Suspect”. A very Frequent Cause for Diarrhoea after Treatment for many different Cancer Types

Introduction Approximately 16,000 patients per year are left with a chronic change in bowel function and gastrointestinal symptoms following treatment for cancer. This can have a significant impact upon quality of life and even compromise on-going cancer therapy. Previous small studies focusing mainly on patients with gynaecological cancers suggest that bile acid malabsorption (BAM) may be an important cause of radiotherapy-induced diarrhoea. This retrospective study aims to elucidate the prevalence of BAM in patients referred to a specialist gastroenterology clinic which treats patients with consequences of cancer treatments. Methods Patients referred to our clinic are managed using a peer reviewed algorithm. If they report diarrhoea, defined as Bristol Stool Chart type 6–7, a routine referral for a SeHCAT (75-selenium homocholic acid taurine) scan is made to exclude BAM. BAM is diagnosed when the SeHCAT 7 day retention is Results Between 2009–2012, 262 patients were referred for a SeHCAT scan. 139 (53.1%) were male (median age 66, range 32–89) and 123 (46.9%) female (median age 61, range 20–86). 79 (37%) patients had been treated for gynaecological, 94 (44%) for urological, 41 (19%) for anorectal and 30 (11%) for upper gastrointestinal tract cancers. A further 18 (7%) were treated for other cancer types (breast, lung and haematological). BAM was diagnosed in 24 patients (25%) treated for urological cancers, with 17% (n = 4) having severe BAM. 46 patients (58%) treated for gynaecological cancers had BAM, severe in 57% (n = 26). BAM was diagnosed in 22 patients (54%) treated for anorectal cancers, with 55% having severe BAM (n = 12). In 15 patients (50%) treated for upper GI cancers, the majority (73%) had severe BAM (n = 11). For patients with other cancer types, BAM was diagnosed in 8 patients (44%) with severe BAM in 2 of these (25%). Conclusion The frequency of severe bile acid malabsorption and its impact on quality of life is poorly appreciated amongst those who treat cancer. BAM is a common problem in patients treated for a wide variety of cancers with a number of different treatment modalities. Given the effectiveness of dietary fat manipulation combined with a new generation of bile acid sequestrants, SeHCAT scanning should be a first line in investigating patients with diarrhoea after cancer therapies. Disclosure of Interest None Declared

Impact of APOE genotype on postprandial Sf&gt;400 lipid and apolipoprotein B-48 responses to dietary fat manipulation – insights from the SATgenε study

Impact of <i>APOE</i> genotype on postprandial S_f&gt;400 lipid and apolipoprotein B-48 responses to dietary fat manipulation – insights from the SATgenε study

APOE genotype influences triglyceride and C-reactive protein responses to altered dietary fat intake in UK adults

The response of plasma lipids to dietary fat manipulation is highly heterogeneous, with some indications that APOE genotype may be important. The objective was to use a prospective recruitment approach to determine the effect of dietary fat quantity and composition on both lipid and nonlipid cardiovascular disease biomarkers according to APOE genotype. Participants had a mean (±SD) age of 51 ± 9 y and a BMI (in kg/m²) of 26.0 ± 3.8 (n = 44 E3/E3, n = 44 E3/E4) and followed a sequential dietary intervention (the SATgenε study) in which they were assigned to a low-fat diet, a high-fat high-SFA (HSF) diet, and the HSF diet with 3.45 g DHA/d (HSF-DHA), each for 8 wk. Fasting blood samples were collected at the end of each intervention arm. An overall diet effect was evident for all cholesterol fractions (P < 0.01), with no significant genotype × diet interactions observed. A genotype × diet interaction (P = 0.033) was evident for plasma triglycerides, with 17% and 30% decreases in APOE3/E3 and APOE3/E4 individuals after the HSF-DHA diet relative to the low-fat diet. A significant genotype × diet interaction (P = 0.009) was also observed for C-reactive protein (CRP), with only significant increases in concentrations after the HSF and HSF-DHA diets relative to the low-fat diet in the APOE3/E4 group (P < 0.015). Relative to the wild-type APOE3/E3 group, our results indicate a greater sensitivity of fasting triglycerides and CRP to dietary fat manipulation in those with an APOE3/E4 genotype (25% population), with no effect of this allelic profile on cholesterol concentrations.

Dietary fat manipulation has a greater impact on postprandial lipid metabolism than the apolipoprotein E (epsilon) genotype–insights from the SATgenε study

Our aim was to determine the effects of chronic dietary fat manipulation on postprandial lipaemia according to apolipoprotein (APO)E genotype. Men (mean age 53 (SD 9) years), prospectively recruited for the APOE genotype (n = 12 E3/E3, n = 11 E3/E4), were assigned to a low fat (LF), high fat, high-saturated fat (HSF), and HSF diet with 3.45 g/day docosahexaenoic acid (HSF-DHA), each for an 8-week period in the same order. At the end of each dietary period, a postprandial assessment was performed using a test meal with a macronutrient profile representative of that dietary intervention. A variable postprandial plasma triacylglycerol (TAG) response according to APOE genotype was evident, with a greater sensitivity to the TAG-lowering effects of DHA in APOE4 carriers (p ≤ 0.005). There was a lack of an independent genotype effect on any of the lipid measures. In the groups combined, dietary fat manipulation had a significant impact on lipids in plasma and Svedberg flotation rate (S(f) ) 60-400 TAG-rich lipoprotein fraction, with lower responses following the HSF-DHA than HSF intervention (p < 0.05). Although a modest impact of APOE genotype was observed on the plasma TAG profile, dietary fat manipulation emerged as a greater modulator of the postprandial lipid response in normolipidaemic men.

SATgenɛ dietary model to implement diets of differing fat composition in prospectively genotyped groups (apoE) using commercially available foods

Response to dietary fat manipulation is highly heterogeneous, yet generic population-based recommendations aimed at reducing the burden of CVD are given. The APOE epsilon genotype has been proposed to be an important determinant of this response. The present study reports on the dietary strategy employed in the SATgenε (SATurated fat and gene APOE) study, to assess the impact of altered fat content and composition on the blood lipid profile according to the APOE genotype. A flexible dietary exchange model was developed to implement three isoenergetic diets: a low-fat (LF) diet (target composition: 24 % of energy (%E) as fat, 8 %E SFA and 59 %E carbohydrate), a high-saturated fat (HSF) diet (38 %E fat, 18 %E SFA and 45 %E carbohydrate) and a HSF-DHA diet (HSF diet with 3 g DHA/d). Free-living participants (n 88; n 44 E3/E3 and n 44 E3/E4) followed the diets in a sequential design for 8 weeks, each using commercially available spreads, oils and snacks with specific fatty acid profiles. Dietary compositional targets were broadly met with significantly higher total fat (42·8 %E and 41·0 %E v. 25·1 %E, P ≤ 0·0011) and SFA (19·3 %E and 18·6 %E v. 8·33 %E, P ≤ 0·0011) intakes during the HSF and HSF-DHA diets compared with the LF diet, in addition to significantly higher DHA intake during the HSF-DHA diet (P ≤ 0·0011). Plasma phospholipid fatty acid analysis revealed a 2-fold increase in the proportion of DHA after consumption of the HSF-DHA diet for 8 weeks, which was independent of the APOE genotype. In summary, the dietary strategy was successfully implemented in a free-living population resulting in well-tolerated diets which broadly met the dietary targets set.

Dietary fat manipulation and not apolipoprotein E (epsilon) genotype has a significant impact on cytokine production – insights from the SATgenε study

Dietary fat manipulation and not apolipoprotein E (epsilon) genotype has a significant impact on cytokine production – insights from the SATgenε study

SATgenε dietary strategy to investigate the impact of the apo E genotype on LDL-cholesterol response to dietary fat manipulation

SATgenε dietary strategy to investigate the impact of the <i>apo E</i> genotype on LDL-cholesterol response to dietary fat manipulation

Energy-restricted diets result in higher numbers of CD4+, CD8+, immunoglobulins (A, M, and G), and CD45RA cells in spleen and CD4+, immunoglobulin A, and CD45RA cells in colonic lamina propria of rats

Dietary energy restriction (ER) offers certain health benefits, particularly when ER is controlled through manipulation of dietary fats. Our hypothesis is that cellular immunity is modulated by dietary ER. Furthermore, we believe that the immune response may differ between spleen and colon because their lymphatic and vascular organization is different. The objective of the study was to test this hypothesis by determining the effects of dietary ER through manipulation of energy intake from high-fat (HF) diets on the expression and frequency of the CD4(+) (T-helper/T-inducer) and CD8(+) (T-cytotoxic/T-suppressor) cells, CD45RA (B-cell-specific marker), and immunoglobulins (Ig) A-, G-, and M-bearing cells in spleen and colon in rats by immunohistochemical method. Rats fed the HF diet had a significantly (P < .05) reduced number of immune cells as compared with those fed ER diets. Energy-restricted diet-fed rats showed higher (P < .05) numbers of CD4(+), CD8(+), IgA, IgM, IgG, and CD45RA cells in spleen and CD4(+), IgA, and CD45RA cells in colonic lamina propria. The IgA-containing cells were markedly higher in the colon compared with the spleen. No change occurred in the number of IgM- and IgG-containing cells in colonic tissues between groups, except for the 20% ER group where IgM-labeled cells were higher (P < .05) compared with HF and 40% ER groups. These findings suggest that ER may modulate adaptive immune function and that CD4(+) and IgA cells may serve as biological indicators for dietary energy-modulated immunoresponse in spleen and colon, respectively.

Dietary fish oil reverses lipotoxicity, altered glucose metabolism, and nPKC ε translocation in the heart of dyslipemic insulin-resistant rats

The present study analyzes several markers of energy metabolism in the heart muscle of dyslipemic insulin-resistant rats fed a sucrose-rich diet (SRD, 62.5% wt/wt) for 8 months. It also explores the possible beneficial effects of dietary fish oil supplementation on cardiac lipids and glucose metabolism. With this purpose, male Wistar rats were fed an SRD for 6 months. Whereas half of the animals continued with the same diet for up to 8 months, the other half was fed an SRD in which fish oil (7% + 1% corn oil wt/wt) replaced corn oil (8% wt/wt) from months 6 to 8. The results were compared with rats fed a control diet (starch 62.5% wt/wt). The cardiac muscle of SRD-fed rats showed (1) a significant reduction ( P < .05) in key enzymes activities and metabolites involved in glucose metabolism, accompanied by a significant ( P < .05) increase of lipid storage (triglyceride, long-chain acyl coenzyme A, and diacylglycerol), and (2) a significant increase ( P < .05) of nPKC ε protein mass expression in the membrane fraction without changes in the cPKC βII. Dietary fish oil, which reduces the availability of plasma lipid flux and normalizes glucose homeostasis, was able to reverse heart muscle lipotoxicity. Fish oil benefits key enzymes activities in glucose metabolism and normalizes glycogen and glucose-6-phosphate concentration, and the altered nPKC ε protein mass expression translocation in the heart of SRD-fed rats. Our findings suggest that manipulation of dietary fats may play a key role in the management of lipid disorders, offering a protection against the development of cardiovascular diseases.