High-Fat Diets Containing Different Types of Fatty Acids Modulate Gut-Brain Axis in Obese Mice

Background: Excessive consumption of high-fat diets is associated with disordered metabolic responses, which may lead to chronic diseases. High-fat diets containing different types of fatty acids lead to distinct alterations in metabolic responses of gut-brain axis. Methods: In our study, normal male C57BL/6J mice were fed to multiple high fatty acid diets (long-chain and medium-chain saturated fatty acid, LCSFA and MCSFA group; n-3 and n-6 polyunsaturated fatty acid, n-3 and n-6 PUFA group; monounsaturated fatty acid, MUFA group; trans fatty acid, TFA group) and a basic diet (control, CON group) for 19 weeks. To investigate the effects of high-fat diets on metabolic responses of gut-brain axis in obese mice, blood lipids were detected by fast gas chromatography, and related proteins in brain and intestine were detected using Western blotting, ELISA, and immunochemistry analysis. Results: All high-fat diets regardless of their fatty acid composition induced obesity, lipid disorders, intestinal barrier dysfunction, and changes in gut-brain axis related factors except basal diet in mice. For example, the protein expression of zonula occludens-1 (ZO-1) in ileum in the n-3 PUFA group was higher than those in the MCSFA and CON group (all Ps < 0.05). The expressions of insulin in hippocampus and leptin in ileum in the MCSFA group were all higher than those in other groups (all Ps < 0.05). Conclusions: The high MCSFA diet had the most effect on metabolic disorders, and the high n-3 PUFA diet had the least effect on changes in metabolism.

Effects of perioperative intravenous ω-3 fatty acids in colon cancer patients: a randomized, double-blind, placebo-controlled clinical trial

ABSTRACT Background The postoperative inflammatory response contributes to tissue healing and recovery but overwhelming inflammation is associated with postoperative complications. n–3 (ω-3) PUFAs modulate inflammatory responses and may help to prevent a proinflammatory cascade. Objectives We aimed to investigate the effects of perioperative intravenous n–3 PUFAs on inflammatory cytokines in colon cancer surgery. Methods This study is a randomized, double-blind, placebo-controlled clinical trial. Forty-four patients undergoing elective colon resection for nonmetastasized cancer were randomly assigned to 2 intravenous n–3 PUFA or saline control infusions the night before and the morning after surgery. Blood was sampled at 6 perioperative time points for changes in cytokines in serum and in LPS-stimulated whole blood samples and leukocyte membrane fatty acid profiles. Results Twenty-three patients received saline and 21 patients received n–3 PUFAs. Patient and operation characteristics were equal between groups, except for open resection (saline n = 5 compared with n–3 PUFA n = 0, P = 0.056). Ex-vivo IL-6 after LPS stimulation was significantly higher in the n–3 PUFA group at the first day after surgery (P = 0.014), but not different at the second day after surgery (P = 0.467). White blood cell count was higher in the n–3 PUFA group at the fourth day after surgery (P = 0.029). There were more patients with infectious complications in the n–3 PUFA group (8 compared with 3, P = 0.036). There were no overall differences in serum IL-6, IL-10, C-reactive protein, and length of stay. The administration of n–3 PUFAs resulted in rapid increases in leukocyte membrane n–3 PUFA content. Conclusions In the n–3 PUFA group a clear relation with serum and LPS-stimulated cytokines was not found but, unexpectedly, more infectious complications occurred. Caution is thus required with the off-label use of a perioperative intravenous n–3 PUFA emulsion as a standalone infusion in the time sequence reported in the present study in colon resections with primary anastomosis. This trial was registered at clinicaltrials.gov as NCT02231203.

BMI modifies the effect of dietary fat on atherogenic lipids: a randomized clinical trial

ABSTRACT Background SFA intake increases LDL cholesterol whereas PUFA intake lowers it. Whether the lipid response to dietary fat differs between normal-weight and obese persons is of relevance to dietary recommendations for obese populations. Objectives We compared the effect of substituting unsaturated fat for saturated fat on LDL cholesterol and apoB concentrations in normal-weight (BMI ≤ 25 kg/m2) and obese (BMI: 30–45) subjects with elevated LDL cholesterol. Methods We randomly assigned 83 men and women (aged 21–70 y) stratified by BMI (normal: n = 44; obese: n = 39) and elevated LDL cholesterol (mean ± SD, normal weight 4.6 ± 0.9 mmol/L; obese 4.4 ± 0.8 mmol/L) to either a PUFA diet enriched with oil-based margarine ( n = 42) or an SFA diet enriched with butter (n = 41) for 6 wk. Results Seven-day dietary records showed differences of ∼9 energy percent (E%) in SFA and ∼4 E% in PUFA between the SFA and PUFA groups. In the total study population, the PUFA diet compared with the SFA diet lowered LDL cholesterol (−0.31 mmol/L; 95% CI: −0.47, −0.15 mmol/L, compared with 0.32 mmol/L; 95% CI: 0.18, 0.47 mmol/L; P < 0.001) and apoB (−0.08 g/L; 95% CI: −0.11, −0.05 g/L, compared with 0.07 g/L; 95% CI: 0.03, 0.10 g/L; P < 0.001). Tests of the BMI × diet interaction were significant for total cholesterol, LDL cholesterol, and apoB ( P values ≤ 0.009). In normal-weight compared with obese participants post-hoc comparisons found that the respective changes in LDL cholesterol were 9.7% (95% CI: 5.3%, 14.2%) compared with 5.3% (95% CI: −0.7%, 11.2%), P = 0.206, in the SFA group, and −10.4% (95% CI: −15.2%, −5.7%) compared with −2.3% (95% CI: −7.4%, 2.8%), P = 0.020, in the PUFA group. ApoB changes were 7.5% (95% CI: 3.5%, 11.4%) compared with 3.0% (95% CI: −1.7%, 7.7%), P = 0.140, in the SFA group, and −8.9% (95% CI: −12.6%, −5.2%) compared with −3.8% (95% CI: −6.3%, −1.2%), P = 0.021, in the PUFA group. Responses to dietary fat were not associated with changes in polyprotein convertase subtisilin/kexin type 9 concentrations. Conclusions BMI modifies the effect of PUFAs compared with SFAs, with smaller improvements in atherogenic lipid concentrations in obese than in normal-weight individuals, possibly supporting adjustment of dietary recommendations according to BMI. This trial was registered with www.clinicaltrials.gov as NCT02589769.

Combining Dietary Sulfur Amino Acid Restriction with Polyunsaturated Fatty Acid Intake in Humans: A Randomized Controlled Pilot Trial

Dietary and plasma total cysteine (tCys) have been associated with adiposity, possibly through interaction with stearoyl–CoA desaturase (SCD), which is an enzyme that is involved in fatty acid and energy metabolism. We evaluated the effect of a dietary intervention with low cysteine and methionine and high polyunsaturated fatty acids (PUFAs) on plasma and urinary sulfur amino acids and SCD activity indices. Fourteen normal-weight healthy subjects were randomized to a seven-day diet low in cysteine and methionine and high in PUFAs (Cys/Metlow + PUFA), or high in saturated fatty acids (SFA), cysteine, and methionine (Cys/Methigh + SFA). Compared with the Cys/Methigh + SFA group, plasma methionine and cystathionine decreased (p-values < 0.05), whereas cystine tended to increase (p = 0.06) in the Cys/Metlow + PUFA group. Plasma total cysteine (tCys) was not significantly different between the groups. Urinary cysteine and taurine decreased in the Cys/Metlow + PUFA group compared with the Cys/Methigh + SFA group (p-values < 0.05). Plasma SCD-activity indices were not different between the groups, but the change in cystine correlated with the SCD-16 index in the Cys/Metlow + PUFA group. A diet low in methionine and cysteine decreased plasma methionine and urinary cysteine and taurine. Plasma tCys was unchanged, suggesting that compensatory mechanisms are activated during methionine and cysteine restriction to maintain plasma tCys.

The correlation between untreated caries and the nutritional status of 6–12 years old children in the Medan Maimun and Medan Marelan sub-district

Background: In Indonesia, dental caries constitute one of the most common dental health problems in children. Untreated dental caries will cause both pain and inconvenience when eating, resulting in a reduced appetite which can negatively affect the Body Mass Index (BMI). Purpose: This study aimed to investigate the correlation between untreated caries and nutritional status in children aged 6-12 years old in the Medan Maimun and Medan Marelan sub-districts. Methods: An analytical observation study with cross-sectional design was adopted. The number of child subjects totaled 350, divided into two groups, namely; the PUFA/pufa group (n=172) and the Non-PUFA/pufa group (n=178). Samples were selected on the basis of purposive sampling. Oral examination was subsequently performed using the PUFA/pufa index. The height and weight of the subjects were assessed according to the Indonesian Ministry of Health’s BMI criteria of 2011. Thereafter, Chi square, Spearman and Mann-Whitney tests were all performed as analytical tests. Results: The results of this research revealed a significant correlation between caries status and BMI (p<0.001) in both the PUFA/pufa and Non PUFA/pufa groups (r=-0.515), as well as between the mean PUFA/pufa score and age. However, there was no significant correlation between the mean PUFA/pufa score and gender. Conclusion: It can be concluded that a correlation exists between untreated caries and the nutritional condition of children aged 6-12 years old in the Medan Maimun and Medan Marelan sub-districts.

Addition of omega-3 fatty acid and coenzyme Q10 to statin therapy in patients with combined dyslipidemia

Background:Statins represent a group of drugs that are currently indicated in the primary and secondary prevention of cardiovascular events. Their administration can be associated with side effects and the insufficient reduction of triacylglyceride (TAG) levels. This study aimed to assess the effect of the triple combination of statins with omega-3 fatty acids and coenzyme Q10 (CoQ10) on parameters associated with atherogenesis and statin side effects.Methods:In this pilot randomized double-blind trial, 105 subjects who met the criteria of combined dislipidemia and elevated TAG levels were randomly divided into three groups. In the control group, unaltered statin therapy was indicated. In the second and third groups, omega-3 PUFA 2.52 g/day (Results:Significant reduction of hepatic enzymes activity, systolic blood preasure, inflammatory markers and TAG levels were detected in both groups in comparison to the control group. Activity of SOD and GPx increased significantly after additive therapy. Coenzyme Q10 addition significantly reduced most of the abovementioned parameters (systolic blood preasure, total cholesterol, LDL, hsCRP, IL-6, SOD) in comparison with the statin+omega-3 PUFA group. The intensity of statin adverse effects were significantly reduced in the group with the addition of CoQ10.Conclusions:The results of this pilot study suggest the possible beneficial effects of triple combination on the lipid and non-lipid parameters related to atherogenesis and side effects of statin treatment.

Lipid metabolism and the risk factors of cardiovascular disease: implication of dietary omega-3 polyunsaturated fatty acids

Cardiovascular disease (CVD) is a complicated and multifarious disease, and is the number one cause of mortality worldwide. The pathogenesis of CVD is attributed to the interaction between genetics and environment. There are numerous data that support the cardioprotective properties of omega (n)-3 polyunsaturated fatty acids (PUFA); however, there are also controversial reports. Considering the reported sex and age differences in the pathophysiology of CVD and the metabolism of n-3 PUFA, it is imperative to consider these factors in the cardioprotective effects of n-3 PUFA. The current thesis investigated the effects of n-3 PUFA on the risk factors of CVD, such as dyslipidemia and obesity, with a particular focus on how sex, age, and dose of n-3 PUFA affect lipid and lipoprotein metabolism. The plasma concentrations of lipids and lipoproteins of C57BL/6 mice offspring at weaning and 16 weeks postweaning were chosen as study outcomes to assess the sex, age, and dose-specific effects of n-3 PUFA on markers of dyslipidemia, a well-known risk factor of CVD. A longer exposure to a postnatal diet high in n-3 PUFA increased plasma concentration of low-density lipoprotein (LDL) cholesterol in the offspring in a sex-specific manner; however, the profile of this increase was less atherogenic, as the high n-3 PUFA group had a lower plasma concentration of very small LDL particles in both males and females. There was no effect of high n-3 PUFA diet observed on plasma concentration of high-density lipoprotein cholesterol; however, the high n-3 PUFA group had a higher cholesterol efflux in the male offspring but not in female offspring. Lipidomic analyses revealed that high n-3 PUFA diet led to higher hepatic and plasma concentrations of n-3 PUFA-containing bioactive lipids, such a phosphatidylcholine, lysophosphatidylcholine and free fatty acids, which could positively influence pathways involved in cardioprotection. The effects of dietary n-3 PUFA on obesity at the cellular level was also investigated, using adipocyte hypertrophy as the outcome measure of adipose tissue enlargement. A diet high in n-3 PUFA prevented adipocyte hypertrophy in males, with no effect in females. High n-3 PUFA diet also led to the downregulation of the messenger RNA expression of acyl-CoA:diacylglycerol acyltransferase 2, fatty acid binding protein-4, peroxisome proliferator-activated receptor protein γ, and leptin in males, which are key proteins involved in adipocyte hypertrophy; however, no effect was observed in females. The last study assessed the effects of dose and duration of exposure to dietary n-3 PUFA on docosahexaenoic acid accretion in the brain, and the expression of neurotrophins known to have neuroprotective and cardioprotective benefits. Dietary n-3 PUFA led to an age-dependent increase in the expression of brain-derived neurotrophic factor, tropomyosin receptor kinase, and phosphorylated cyclic AMP response element binding protein. In conclusion, the results from the current thesis demonstrate a sex-, dose-, and age-specific effect of n-3 PUFA on risk factors of CVD, and on novel regulatory pathways by which n-3 PUFA could reduce dyslipidemia and obesity. The results also suggest that n-3 PUFA could be neuroprotective and cardioprotective through a common neurotrophin signalling pathway.

Orally administered [14C]DPA and [14C]DHA are metabolised differently to [14C]EPA in rats

Previous studies have revealed that C20 PUFA are significantly less oxidised to CO2 in whole-body studies compared with SFA, MUFA and C18 PUFA. The present study determined the extent to which three long-chain PUFA, namely 20 : 5n-3 EPA, 22 : 5n-3 docosapentaenoic acid (DPA) and 22 : 6n-3 DHA, were catabolised to CO2 or, conversely, incorporated into tissue lipids. Rats were administered a single oral dose of 2·5 μCi [1-14C]DPA, [1-14C]EPA, [1-14C]DHA or [1-14C]oleic acid (18 : 1n-9; OA), and were placed in a metabolism chamber for 6 h where exhaled 14CO2 was trapped and counted for radioactivity. Rats were euthanised after 24 h and tissues were removed for analysis of radioactivity in tissue lipids. The results showed that DPA and DHA were catabolised to CO2 significantly less compared with EPA and OA (P< 0·05). The phospholipid (PL) fraction was the most labelled for all three n-3 PUFA compared with OA in all tissues, and there was no difference between C20 and C22 n-3 PUFA in the proportion of label in the PL fraction. The DHA and DPA groups showed significantly more label than the EPA group in both skeletal muscle and heart. In the brain and heart tissue, there was significantly less label in the cholesterol fraction from the C22 n-3 PUFA group compared with the C20 n-3 PUFA group. The higher incorporation of DHA and DPA into the heart and skeletal muscle, compared with EPA, suggests that these C22 n-3 PUFA might play an important role in these tissues.

Evaluation of maize grain and polyunsaturated fatty acid (PUFA) as energy sources for breeding rams based on hormonal, sperm functional parameters and fertility

The objective of the present study was to elucidate the effect of different sources of dietary energy (maize vs polyunsaturated fatty acid (PUFA) on semen functional parameters and fertility of adult rams. Eighteen adult rams were divided into two groups (maize and PUFA, n = 9). The main energy source for the rams in the maize group was coarsely ground maize grain, whereas in the PUFA group it was sunflower oil (rich in 18 : 2 linoleic acid, an omega-6 acid). The ration was fed for a minimum period of 60 days and thereafter semen was collected for evaluation. The proportion of progressive forward motility was significantly (P < 0.05) higher in the PUFA group compared with the maize group. Sperm lipid peroxidation as measured by malondialdehyde formation (µM per 1 × 109 spermatozoa) was significantly (P < 0.05) higher in the PUFA group compared with the maize group. When the semen was diluted with Tris–egg yolk–citrate buffer and incubated for 24 h at 4°C, the proportions of plasmalemma integrity, the sperm subpopulation positive for functional membrane and acrosomal integrities, and mitochondrial membrane potential were significantly (P < 0.05) higher in PUFA-fed than in maize-fed animals. The different sources of energy did not influence the serum and seminal plasma IGF-I levels. The cleavage rate (percentage) did not differ significantly between PUFA- (45.4 ± 4.91) and maize- (44.63 ± 6.8) fed animals. In conclusion, PUFA feeding influenced sperm quality by altering or stabilising membrane integrity. The present study indicates that PUFA may improve semen quality but did not improve in vitro fertilisation.

The Influence of Season on the Gonad Index and Biochemical Composition of the Sea UrchinParacentrotus lividusfrom the Golf of Tunis

Seasonal variation in the gonad weight and biochemical composition of the sea urchinParacentrotus lividusfrom the Golf of Tunis (Tunisia) were studied between September 2003 and August 2004. The highest gonad indices occurred in March (16.71%). The spawning period occurred between April and July and resulted in a fall in gonad indices to low level (7.12 ± 0.12%). Protein constituted the main component of the gonad, and lipid and carbohydrate were found at appreciable amounts. Consistent with the gonad cycle, sea urchin biochemical components showed clear seasonal variation with a significant decrease during the spawning period. The polyunsaturated fatty acid (PUFA) group was found at high level (40% of the total fatty acids). Of the PUFA group, eicosapentaenoic (C20:5n−3) and eicosatetraenoic (C20:4n−3) were the most abundant gonadal lipids. The level of PUFA was significantly affected by temperature variation showing an increase during the cold months and a decrease in the hot months.