Dietary fatty acids intake and all-cause and cardiovascular mortality in patients on peritoneal dialysis.

BACKGROUND & AIMS: The relationship between dietary fatty acids (FA) and clinical outcomes are relatively lacking in non-dialyzed and dialyzed chronic kidney disease (CKD) population, resulting in insufficient guide about the dietary FA intake in this population. In this study, we aimed to observe the association between the intake of total or different types of FA and all-cause and cardiovascular (CV) mortality in patients undergoing peritoneal dialysis (PD). METHODS: This is a prospective cohort study with data retrospectively analyzed in 881 patients undergoing PD. Dietary FA intake measured by 3-day dietary records. The outcomes were defined as all-cause and CV death. Baseline FA intake and time-averaged FA intake were categorized by tertiles based on the distribution among the study population. We used univariate and multivariate Cox proportional regression models to determine the association between amounts and types of FA and all-cause and CV mortality. RESULTS: During a median follow up of 45 months, 93 patients were still being maintained on PD, 467 had died, including 189 (40.5%) attributable to CV death. Compared to patients in the low tertile of total FA (TFA) intake at baseline group, the middle or/and high tertile groups were more likely to be male, younger, well-educated and better nutritional status (P < 0.05). At the baseline, no association was found between all-cause and CV death in either total or different types of FA after adjusting for nutritional variables. As for time-averaged analyses, the associations of TFA, saturated FA (SFA), monounsaturated FA (MUFA), ω-3 and ω-6 polyunsaturated FA (PUFA) and all-cause mortality were weakened after adjustment for laboratory and nutrients variables. However, PUFA independently reduced 5% of mortality even after adjustment for laboratory and nutrients variables [HR 0.95 (0.91, 0.99), P = 0.023], and the ratio of MUFA/PUFA was positively associated with the risk for all-cause mortality [HR 1.05 (1.01, 1.09), P = 0.008]. Furthermore, each 10% increase of the ratio of ω-6/ω-3 was only weakly associated with the risk for all-cause mortality [HR 1.02 (1.00, 1.04), P = 0.034]. As for CVD mortality, the impacts of total and each type of FA disappeared after adjustment for laboratory or nutrients variables. CONCLUSIONS: Time-averaged PUFA intake was independently associated with a lower risk for all-cause mortality in our PD cohort, while the higher ratio of MUFA/PUFA and ω-6/ω-3 increased all-cause mortality. More observational and interventional researches are needed to determine these associations.

Dietary Saturated, Monounsaturated, or Polyunsaturated Fatty Acids and Estimated 10-Year Risk of a First Hard Cardiovascular Event.

BACKGROUND: The effects of dietary saturated, monounsaturated, or polyunsaturated fatty acids on the risk of cardiovascular events remain controversial. METHODS: This cross-sectional study was performed in 4211 patients, aged 40 to 79 years, from the National Health and Nutrition Examination Survey between 1999 and 2018. The independent variables were saturated fatty acids, monounsaturated fatty acids, and polyunsaturated fatty acids. The dependent variable was the 10-year risk of a first hard atherosclerotic cardiovascular event. The other variables were considered as the potential confounding factors. Multivariate linear regression models and smooth curve fittings were used to evaluate the association between saturated fatty acids, polyunsaturated fatty acids, or monounsaturated fatty acids and the 10-year risk. RESULTS: There was no association between dietary saturated fatty acids and 10-year risk after adjusting for all the potential confounding factors; 10-year risk decreased by 0.022% each 1-g increase in monounsaturated fatty acids intake from 0 to 153.772 g, and 0.025% each 1-g increase in polyunsaturated fatty acids intake from 0 to 98.323 g, respectively. Moreover, subgroup analysis showed that monounsaturated fatty acids and polyunsaturated fatty acids were both negatively correlated to 10-year risk in nondiabetes and non-high-low-density lipoprotein patients; monounsaturated fatty acids were also negatively associated with 10-year risk in hypertensive patients. CONCLUSIONS: There was no association between dietary saturated fatty acids and 10-year risk. Increased dietary intake of monounsaturated fatty acids or polyunsaturated fatty acids decreased 10-year risk, particularly in nondiabetes, non-high-low density lipoprotein patients.

Dietary Fats and Depressive Symptoms in Italian Adults.

BACKGROUND: Depression represents one of the major causes of disability worldwide, with an important socioeconomic cost. Although many risk factors have been considered in its pathogenesis, nutrition seems to play a determinant role in its prevention. With regard to individual macronutrients, dietary fats and especially n-3 polyunsaturated fatty acids (n-3 PUFA) are the most studied. However, previous data about other dietary fatty acids, such as n-6 PUFA, are conflicting, and little is known about saturated fatty acids (SFA), especially when considering carbon chain length. Thus, we investigated whether single types and subtypes of dietary fats are related to depressive symptoms in Italian individuals living in the Mediterranean area. METHODS: Dietary and socio-demographic data of 1572 individuals were analyzed. Food frequency questionnaires (FFQs) were used to determine the consumption of total dietary fat and each specific class of dietary fat, such as SFA, monounsaturated fatty acid (MUFA), and PUFA. The intake of fatty acids was also assessed according to the carbon-chain length of each single class. The Center for Epidemiologic Studies Depression Scale (CES-D) was used as a screening tool for depressive symptoms. RESULTS: After adjustment for potential confounding factors, a significant inverse association between low/moderate levels of PUFA intake and depressive symptoms (Q2 vs. Q1, odds ratio (OR) = 0.60, 95% CI: 0.44, 0.84) was found. On the other hand, moderate saturated fat consumption was associated with depressive symptoms (Q3 vs. Q1, OR = 1.44, 95% CI: 1.02, 2.04). However, when considering carbon chain length, individuals with a lower to moderate intake of short-chain saturated fatty acids (SCSFA) and medium-chain saturated fatty acids (MCSFA) were less likely to have depressive symptoms (Q3 vs. Q1, OR = 0.48, 95% CI: 0.31, 0.75), while moderate intake of arachidic acid (C20:0) was directly associated with depressive symptoms (Q3 vs. Q1, OR = 1.87, 95% CI: 1.26, 2.77). Among single MUFAs, higher myristoleic acid (C14:1) intake was directly associated with depressive symptoms (Q4 vs. Q1, OR = 1.71, 95% CI: 1.12, 2.61), while moderate intake of erucic acid (C22:1) was associated with lower odds of having depressive symptoms (Q3 vs. Q1, OR = 0.54, 95% CI: 0.33, 0.86). When considering individual PUFAs, individuals with moderate and higher intakes of arachidonic acid (C20:4) were less likely to have depressive symptoms (OR = 0.64, 95% CI: 0.45, 0.91; OR = 0.59, 95% CI: 0.38, 0.91, respectively). Similarly, higher eicosapentaenoic acid (C20:5) intake was inversely associated with depressive symptoms (Q4 vs. Q1, OR = 0.35, 95% CI: 0.12, 0.98), while a significant association for docosahexaenoic acid (C22:6) was retrieved only for low intakes (Q2 vs. Q1, OR = 0.33, 95% CI: 0.12, 0.88). CONCLUSIONS: Dietary fat intake may be associated with depressive symptoms, underlying the importance of distinguishing between different fat types. This study confirms the pivotal role of PUFAs and reopens the debate on the role of saturated fatty acids, suggesting plausible effects of moderate intakes of short-chain fatty acids.

Cyclosorus terminans Extract Ameliorates Insulin Resistance and Non-Alcoholic Fatty Liver Disease (NAFLD) in High-Fat Diet (HFD)-Induced Obese Rats.

Interruptins A and B exhibited anti-diabetic, anti-inflammatory, and anti-oxidative effects. This study aimed to investigate the therapeutic ability of extract enriched by interruptins A and B (EEI) from an edible fern Cyclosorus terminans on insulin resistance and non-alcoholic fatty liver disease (NAFLD) in a high-fat diet (HFD)-induced obese rats and elucidate their possible mechanisms. HFD-induced obese rats were treated with EEI for 2 weeks. Real-time polymerase chain reaction (PCR) was used to examine the molecular basis. We found that EEI supplementation significantly attenuated body and liver weight gain, glucose intolerance, and insulin resistance. Concurrently, EEI increased liver and soleus muscle glycogen storage and serum high-density lipoprotein (HDL) levels. EEI also attenuated NAFLD, as indicated by improving liver function. These effects were associated with enhanced expression of insulin signaling genes (Slc2a2, Slc2a4, Irs1 and Irs2) along with diminished expression of inflammatory genes (Il6 and Tnf). Furthermore, EEI led to the suppression of lipogenesis genes, Srebf1 and Fasn, together with an increase in fatty acid oxidation genes, Ppara and Cpt2, in the liver. These findings suggest that EEI could ameliorate HFD-induced insulin resistance and NAFLD via improving insulin signaling pathways, inflammatory response, lipogenesis, and fatty acid oxidation.

Association between Dietary Fatty Acid Patterns and Colorectal Cancer Risk: A Large-Scale Case-Control Study in China.

Associations of dietary fatty acids with the risk of colorectal cancer (CRC) remain controversial. The objective of this study was to examine whether dietary-derived fatty acid patterns were related to CRC risk among Chinese people. A total of 2806 CRC patients and 2806 frequency-matched controls were interviewed in this case-control study between July 2010 and May 2021. A food frequency questionnaire was used to gather information on dietary intake. Four fatty acid patterns were identified using factor analysis. The even-long-chain fatty acid pattern had no statistically significant association with CRC risk (adjusted Odds ratio (aOR), 1.16; 95% confidence interval (CI), 0.97-1.39; ptrend = 0.129). However, significant inverse associations were found between the medium-chain and long-chain saturated fatty acid (SFA) pattern (aOR, 0.34; 95%CI, 0.27-0.42), the highly unsaturated fatty acid pattern (aOR, 0.73; 95%CI, 0.60-0.88), the odd-chain fatty acid pattern (aOR, 0.69; 95%CI, 0.57-0.83), and CRC risk. The interaction between fatty acid patterns and sex was observed, and the association between the highly unsaturated fatty acid pattern and CRC risk differed by subsite. In conclusion, increasing the intakes of foods rich in medium-chain SFAs, highly unsaturated fatty acids, and odd-chain fatty acids may be related to a lower risk of CRC.

Dietary fatty acid patterns and risk of oesophageal squamous cell carcinoma.

Background: To characterize and examine the associations between dietary fatty acid intake patterns and the risk of oesophageal squamous cell carcinoma (ESCC). Methods: A total of 422 patients and 423 controls were recruited. Dietary fatty acids were entered into a factor analysis. Multivariable logistic regression and restricted cubic spline were used to evaluate the risk of ESCC specific for different dietary fatty acid patterns (FAPs). A forest plot was applied to show the association between FAPs and ESCC risk after stratification by lifestyle exposure factors (tobacco smoking, alcohol drinking, pickled food, fried food, hot food, hard food). Results: The factor analysis generated four major fatty acid patterns: a medium- and long-chain SFA (MLC-SFA) pattern; an even-chain unsaturated fatty acid (EC-UFA) pattern, a saturated fatty acid (SFA) pattern and an n-3 long-chain polyunsaturated fatty acid (n-3 LC-PUFA) pattern. In the multivariate-adjusted model, the odds ratios (ORs) with 95% confidence intervals (CIs) of ESCC were 2.07 (1.31, 3.26) and 0.53 (0.34, 0.81) for the highest versus the lowest tertiles of the EC-UFA pattern and n-3 LC-PUFA pattern, respectively. The MLC-SFA and SFA patterns were not associated with ESCC. An association between FAPs and ESCC risk after stratification by lifestyle exposure factors was also observed. Conclusions: Our study indicates that the EC-UFA pattern and n-3 LC-PUFA pattern intake are associated with ESCC, providing a potential dietary intervention for ESCC prevention.

Palm Oil Processing and Controversies over Its Health Effect: Overview of Positive and Negative Consequences.

Palm oil is the world's most commonly used vegetable oil and extracted both from fruit and seed of palm tree. However, its high saturated fatty acid content raised controversies over consumption of the oil. Few scientific findings suggest it as a risk factor for cardiovascular disease and increased consumer's awareness over healthy diet raised claim over it. So that, this article aimed to review literatures on palm oil extraction process and its positive and negative health consequences and besides suggest strategies for healthy diet. Literature search of relevant articles was conducted by using Google scholar, PubMed, Web of science, MEDLINE, World Health Organization library online catalogue, UNICEF library, Open access thesis and dissertations published between 2009 and 2021 explored. Study reports recommend that palmitic acid from vegetable source has less effect on blood total cholesterol and low density lipoprotein cholesterol level as compared to palmitic acid from animal source. In contrary tocotrienols of palm oil lowers blood bad cholesterol level by 7-38%. Moreover, palm oil triacylglycerol arrangement does not have a cardiovascular risk and evidences from available in vitro and in vivo studies are not sufficient enough to conclude palm oil as a causative agent for cardiovascular disease. For healthy diet consumers should avoid trans fatty acids, solid and semi solid oils. Finally, further studies recommended on mitigation strategies to minimize process induced toxicants of palm oil to acceptable level.

Saturated fats and cardiovascular health: Current evidence and controversies.

A diet high in saturated fatty acids (SFA) is a suspected contributor to atherosclerotic cardiovascular disease (ASCVD) risk, in large part because of an effect to raise the low-density lipoprotein cholesterol (LDL-C) concentration. Most dietary guidance from health authorities advocates limiting intake of SFA, particularly for people with clinical ASCVD, dyslipidemia, or diabetes mellitus. However, recent reviews have highlighted controversies regarding SFA intake and cardiovascular health. This brief editorial commentary includes a discussion of the evidence regarding SFA intake and cardiovascular health, outlines gaps in the available evidence, and proposes tentative conclusions based on what is known today about SFA consumption and ASCVD risk. Results from observational studies demonstrate that dietary patterns with lower average intakes of SFA are associated with favorable cardiovascular outcomes. Additionally, although the number of randomized controlled trials testing the effects of reducing SFA intake on ASCVD outcomes is limited, the available evidence supports the view that replacing SFA with unsaturated fatty acids, particularly polyunsaturated fatty acids, may reduce ASCVD risk. Beyond raising LDL-C and atherogenic lipoprotein particle concentrations, higher intakes of SFA may influence pathways affecting inflammation, cardiac rhythm, hemostasis, apolipoprotein CIII production, and high-density lipoprotein function. However, the impacts of these effects on ASCVD risk remain uncertain. In the authors' view, the totality of the evidence supports the current recommendation to limit SFA intake to <10% of total daily energy for the general healthy population and further (e.g., to 5-6% of total daily energy) for patients with hypercholesterolemia.

Association between dietary fat and fat subtypes with the risk of breast cancer in an Iranian population: a case-control study.

AIM: To examine the relationship between dietary fat intake and breast cancer (BC) development. METHOD: This case-control study included 473 women with breast cancer (pathologically confirmed) and 501 healthy subjects matched by age and residency. Dietary intakes of different types and sources of fatty acids were assessed using a validated food frequency questionnaire. The association between dietary fats and odds of BC was assessed using a logistic regression model in crude and multivariable-adjusted models. P values below 0.05 were regarded as statistically significant. RESULTS: Participants' age and body mass index were 44.0 ± 10.8 years and 28.4 ± 5.6 kg/m2, respectively. Individuals with the highest quartile of total fat intake and polyunsaturated fatty acid (PUFA) intake were 1.50 times more at risk to develop BC than others. A positive significant association was observed between animal fat (Q4 vs. Q1, OR = 1.89, 95 % CI = 0.93-3.81), saturated fatty acid (SFA) (Q4 vs. Q1, OR = 1.70, 95 % CI = 0.88-3.30), monounsaturated fatty acid (MUFA) (Q4 vs. Q1 OR = 1.85, 95 % CI = 0.95-3.61) and PUFA intake (Q4 vs. Q1, OR = 2.12, 95 % CI = 1.05-4.27) with BC risk in postmenopausal women. However, there was no association in premenopausal women. CONCLUSIONS: Total dietary fat and its subtypes might increase the risk of BC, especially in postmenopausal women. This observational study confirms the role of dietary fat in breast cancer development. Intervention studies involving different estrogen receptor subgroups are needed.

Effects of ethanol, activated carbon, and activated kaolin on perilla seed oil: Volatile organic compounds, physicochemical characteristics, and fatty acid composition.

Perilla seed oil (PSO) has a special aromatic odor, which is unpleasant to the personal preferences of some consumers. To this end, this article evaluated the differences in volatile organic compounds (VOCs), physicochemical characteristics, and fatty acid composition of PSO treated with ethanol (PSO-EA), activated carbon (PSO-AC), and activated kaolin (PSO-AK). The results showed that in the PSO, PSO-EA, PSO-AC, and PSO-AK samples, the content of linolenic acid, oleic acid, and linoleic acid hardly changed. Among the physicochemical characteristics of the four samples, the color difference between PSO and PSO-EA was greater than the color difference between PSO and PSO-AC, PSO-AK. The three treatment methods had the greatest impact on the PSO peroxide value but had little effect on other indicators. Gas chromatography-ion mobility spectrum results identified 28 known volatiles, of which aldehydes, alkenals, alcohols, ketones, and esters were the main groups. Fingerprint analysis found that PSO had an aromatic odor, which includes 1-hexanol, hexanal, and 2-pentylfuran; the removal effect of ethanol on VOCs in PSO was better than that of activated carbon and activated kaolin. The difference between the four oil samples was found from the strength of the VOCs' signals in a two-dimensional map. From the principal components analysis and the "nearest neighbor" fingerprint analysis, it was found that PSO is generally quite different from PSO-EA, PSO-AC, and PSO-AK, while in the "nearest neighbor" fingerprint analysis, PSO-AC and PSO-AK are similar in general. In short, PSO will have better applications in the food field. PRACTICAL APPLICATION: Treatment of PSO with ethanol, activated carbon, and activated kaolin is conducive to the comprehensive utilization of edible resources. In this work, ethanol, activated carbon, and activated kaolin were used to remove VOCs in PSO, and PSO-EA, PSO-AC, and PSO-AK were obtained. The perilla seed oil after these three treatment methods was tested for VOCs, physicochemical characteristics, and fatty acid composition. They can meet the needs of more consumers without affecting the fatty acid composition in the PSO, and have broad development prospects.

Fatty Acids and Lipid Derivatives Protecting Photooxidative Attack in Age-related Macular Degeneration.

The objective is the systematic review of studies published in Scielo, Redalyc, Dialnet, Web of Science, Scopus and Pubmed, related to the inclusion of fatty acids and lipid derivatives in the daily diet to prevent or delay the appearance or progression of Age-Related Macular Degeneration (AMD). The analysis of the research results consulted shows that AMD is one of the most frequent causes of blindness in subjects over 55 years of age. AMD is characterized by decreased vision, metamorphopsia, macropsies, micropsies, and central scotoma. Disease that must be diagnosed early as it can lead to irreversible blindness. Among the components of the diet that in numerous epidemiological studies have shown an association in the treatment of AMD and that are reviewed in this work are fatty acids, vitamins and carotenoids. There is ample evidence that fatty acids and lipid derivatives can be included in the diet plans of subjects with AMD.

The association between dietary fatty acid intake and the risk of developing preeclampsia: a matched case-control study.

The association between dietary fat intake during pregnancy and the risk of developing preeclampsia has been examined in many epidemiological studies, but the results remain inconsistent. The aim of this study was to clarify this association in pregnant Chinese women. After conducting 1:1 matching, 440 pairs consisting of pregnant women with preeclampsia and hospital-based, healthy pregnant women matched by gestational week (± 1 week) and age (± 3 years) were recruited. A 79-item semi-quantitative food frequency questionnaire administered during face-to-face interviews was used to estimate the participants' dietary intake of fatty acids. We found that the intakes of arachidonic acid (AA), eicosapentaenoic acid (EPA), and docosahexaenoic acid (DHA) were inversely associated with the risk of developing preeclampsia. Compared with the lowest quartile intake, the multivariate-adjusted odds ratios (95% confidence interval) of the highest quartile intake were 0.42 (0.26-0.68, p-trend < 0.001) for EPA, 0.52 (0.3-0.83, p-trend = 0.005) for DHA, and 0.41 (0.19-0.88, p-trend = 0.007) for AA. However, we did not observe any significant associations between the intake of total fatty acids, saturated fatty acids, and mono-unsaturated fatty acids and the risk of developing preeclampsia. Our results showed that the dietary intake of long-chain polyunsaturated fatty acids (i.e., EPA, DHA, and AA) may protect pregnant Chinese women against the development of preeclampsia.

Hypothalamic Inflammation as a Potential Pathophysiologic Basis for the Heterogeneity of Clinical, Hormonal, and Metabolic Presentation in PCOS.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. It is a heterogeneous condition characterized by reproductive, endocrine, metabolic, and psychiatric abnormalities. More than one pathogenic mechanism is involved in its development. On the other hand, the hypothalamus plays a crucial role in many important functions of the body, including weight balance, food intake, and reproduction. A high-fat diet with a large amount of long-chain saturated fatty acids can induce inflammation in the hypothalamus. Hypothalamic neurons can sense extracellular glucose concentrations and participate, with a feedback mechanism, in the regulation of whole-body glucose homeostasis. When consumed nutrients are rich in fat and sugar, and these regulatory mechanisms can trigger inflammatory pathways resulting in hypothalamic inflammation. The latter has been correlated with metabolic diseases, obesity, and depression. In this review, we explore whether the pattern and the expansion of hypothalamic inflammation, as a result of a high-fat and -sugar diet, may contribute to the heterogeneity of the clinical, hormonal, and metabolic presentation in PCOS via pathophysiologic mechanisms affecting specific areas of the hypothalamus. These mechanisms could be potential targets for the development of effective therapies for the treatment of PCOS.

Lipotoxic stress alters the membrane lipid profile of extracellular vesicles released by Huh-7 hepatocarcinoma cells.

Extracellular vesicles (EVs) are well-known mediators in intercellular communication playing pivotal roles in promoting liver inflammation and fibrosis, events associated to hepatic lipotoxicity caused by saturated free fatty acid overloading. However, despite the importance of lipids in EV membrane architecture which, in turn, affects EV biophysical and biological properties, little is known about the lipid asset of EVs released under these conditions. Here, we analyzed phospholipid profile alterations of EVs released by hepatocarcinoma Huh-7 cells under increased membrane lipid saturation induced by supplementation with saturated fatty acid palmitate or Δ9 desaturase inhibition, using oleate, a nontoxic monounsaturated fatty acid, as control. As an increase of membrane lipid saturation induces endoplasmic reticulum (ER) stress, we also analyzed phospholipid rearrangements in EVs released by Huh-7 cells treated with thapsigargin, a conventional ER stress inducer. Results demonstrate that lipotoxic and/or ER stress conditions induced rearrangements not only into cell membrane phospholipids but also into the released EVs. Thus, cell membrane saturation level and/or ER stress are crucial to determine which lipids are discarded via EVs and EV lipid cargos might be useful to discriminate hepatic lipid overloading and ER stress.

Resveratrol confers neuroprotection against high-fat diet in a mouse model of Alzheimer's disease via modulation of proteolytic mechanisms.

Cumulative evidence indicates that excessive consumption of calories from saturated fat contributes to the development of Alzheimer's disease (AD). Here, we assess the triggering and progression of AD pathology induced by a high-fat diet (HFD), and the effects of resveratrol, a polyphenol found in common dietary sources with pleiotropic neuroprotective activities. Over 16 weeks, male wild type (WT) and AD transgenic 5XFAD mice were fed a control diet, HFD (60% kcal from fat), or HFD supplemented with 0.1% resveratrol. Resveratrol protected against HFD-induced memory loss in WT mice and prevented memory loss in 5XFAD mice. Resveratrol also reduced the amyloid burden aggravated by HFD in 5XFAD, and protected against HFD-induced tau pathology in both WT and 5XFAD strains. At the mechanistic level, resveratrol inhibited the HFD-increased amyloidogenic processing of the amyloid precursor protein in both strains; it also restored abnormal high levels in the proteolytic activity of the ubiquitin-proteasome system induced by HFD, suggesting the presence of a compensatory mechanism to counteract the accumulation of aberrant proteins. Thus, our data suggest that resveratrol can correct the harmful effects of HFD in the brain and may be a potential therapeutic agent against obesity-related disorders and AD pathology.

N-3 PUFAs inhibited hepatic ER stress induced by feeding of a high-saturated fat diet accompanied by the expression LOX-1.

Excessive consumption of saturated fat leads to non-alcoholic fatty liver disease (NAFLD), which is attenuated by supplementation of n-3 polyunsaturated fatty acids (PUFAs). Endoplasmic reticulum (ER) stress is crucial in the development of NAFLD, but how high-saturated fat diet (HFD) causes ER stress and NAFLD remains unclear. Lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) is involved in hepatic ER stress. We aimed to explore the roles of LOX-1 in HFD-induced ER stress. Male Sprague-Dawley rats were fed an HFD without or with supplementation of fish oil for 16 weeks. The effects of n-3 PUFAs on hepatic ER stress degrees and the expression levels of LOX-1 were examined. Then human L02 hepatoma cells were treated with palmitate or palmitate and DHA to determine the ER stress and LOX-1 expression levels in vitro. After that the expression of LOX-1 in L02 cells was either knocked-down or overexpressed to analyze the roles of LOX-1 in palmitate-induced ER stress. The feeding of HFD induced NAFLD development and ER stress in the liver, and LOX-1 expressing level, which were all reversed by fish oil supplementation. In vitro, DHA treatment reduced the expression of LOX-1, and palmitate-induced ER stress. SiRNA-mediated knock-down of LOX-1 inhibited palmitate-induced ER stress, whereas overexpression of LOX-1 dramatically induced ER stress in L02 cells.LOX-1 is critical for HFD-induced ER stress, and inhibition of its expression under the treatment of n-3 PUFAs could ameliorate HFD-induced NAFLD.

Dietary fatty acids modulate cortisol concentrations and social dominance during social confrontations in adolescent male guinea pigs.

The hypothalamic-pituitary-adrenal (HPA)-axis and related glucocorticoid concentrations regulate physiology and behavior, which can be modulated by nutritional conditions, particularly by the dietary fatty acid composition. Omega-3 polyunsaturated fatty acids (PUFAs) have been shown to promote hypothalamic-pituitary-adrenal (HPA)-axis functions, whereas saturated fatty acids (SFAs) in general produce adverse effects and even increase baseline glucocorticoid concentrations. Glucocorticoids (e.g. cortisol) were further documented to modulate the establishment of dominance relationships, while the involvement of dietary fatty acids remains understudied. This study focused on different effects of PUFAs and SFAs on cortisol concentrations and social dominance in male guinea pigs. Three groups of animals were maintained on diets high in PUFAs (10 % w/w walnut oil), SFAs (10 % w/w coconut fat), or on an untreated control diet starting already prenatally. During adolescence, at an age of 60, 90, and 120 days, each individual's saliva cortisol concentrations and hierarchy index (calculated by initiated and received agonistic behavior) were measured during basal group housing conditions and stressful social confrontations with unfamiliar individuals of the other groups. SFA males showed highest baseline cortisol concentrations, lowest cortisol responses to social confrontations, and became subdominant. PUFA and control males showed significant cortisol responses. However, while control males became dominant during social confrontations, the hierarchy index in PUFA males decreased with age. Individual hierarchy indices during consecutive social confrontations revealed a high consistency. The findings presented here indicate that dietary fatty acids differently affect HPA-axis functions and social dominance but the underlying mechanisms remain to be determined.

Mitochondrial Dysfunction is a Key Pathway that Links Saturated Fat Intake to the Development and Progression of NAFLD.

Non-Alcoholic fatty liver disease (NAFLD) is the most common form of liver disease and is characterized by fat accumulation in the liver. Hypercaloric diets generally increase hepatic fat accumulation, whereas hypocaloric diets decrease liver fat content. In addition, there is evidence to suggest that moderate amounts of unsaturated fatty acids seems to be protective for the development of a fatty liver, while consumption of saturated fatty acids (SFA) appears to predispose toward hepatic steatosis. Recent studies highlight a key role for mitochondrial dysfunction in the development and progression of NAFLD. It is proposed that changes in mitochondrial structure and function are key mechanisms by which SFA lead to the development and progression of NAFLD. In this review, it is described how SFA intake is associated with liver steatosis and decreases the efficiency of the respiratory transport chain. This results in the production of reactive oxygen species and damage to nearby structures, eventually leading to inflammation, apoptosis, and scarring of the liver. Furthermore, studies demonstrating that SFA intake affects the composition of mitochondrial membranes are presented, and this process accelerates the progression of NAFLD. It is likely that events are intertwined and reinforce each other, leading to a constant deterioration in health.

Intake of dietary fats and fatty acids and the incidence of type 2 diabetes: A systematic review and dose-response meta-analysis of prospective observational studies.

BACKGROUND: The role of fat quantity and quality in type 2 diabetes (T2D) prevention is controversial. Thus, this systematic review and meta-analysis aimed to investigate the associations between intake of dietary fat and fatty acids and T2D, and to evaluate the certainty of evidence. METHODS AND FINDINGS: We systematically searched PubMed and Web of Science through 28 October 2019 for prospective observational studies in adults on the associations between intake of dietary fat and fatty acids and T2D incidence. The systematic literature search and data extraction were conducted independently by 2 researchers. We conducted linear and nonlinear random effects dose-response meta-analyses, calculated summary relative risks (SRRs) with their corresponding 95% confidence intervals (95% CIs), and assessed the certainty of evidence. In total, 15,070 publications were identified in the literature search after the removal of duplicates. Out of the 180 articles screened in full text, 23 studies (19 cohorts) met our inclusion criteria, with 11 studies (6 cohorts) conducted in the US, 7 studies (7 cohorts) in Europe, 4 studies (5 cohorts) in Asia, and 1 study (1 cohort) in Australia. We mainly observed no or weak linear associations between dietary fats and fatty acids and T2D incidence. In nonlinear dose-response meta-analyses, the protective association for vegetable fat and T2D was steeper at lower levels up to 13 g/d (SRR [95% CI]: 0.81 [0.76; 0.88], pnonlinearity = 0.012, n = 5 studies) than at higher levels. Saturated fatty acids showed an apparent protective association above intakes around 17 g/d with T2D (SRR [95% CI]: 0.95 [0.90; 1.00], pnonlinearity = 0.028, n = 11). There was a nonsignificant association of a decrease in T2D incidence for polyunsaturated fatty acid intakes up to 5 g/d (SRR [95% CI]: 0.96 [0.91; 1.01], pnonlinearity = 0.023, n = 8), and for alpha-linolenic acid consumption up to 560 mg/d (SRR [95% CI]: 0.95 [0.90; 1.00], pnonlinearity = 0.014, n = 11), after which the curve rose slightly, remaining close to no association. The association for long-chain omega-3 fatty acids and T2D was approximately linear for intakes up to 270 mg/d (SRR [95% CI]: 1.10 [1.06; 1.15], pnonlinearity < 0.001, n = 16), with a flattening curve thereafter. Certainty of evidence was very low to moderate. Limitations of the study are the high unexplained inconsistency between studies, the measurement of intake of dietary fats and fatty acids via self-report on a food group level, which is likely to lead to measurement errors, and the possible influence of unmeasured confounders on the findings. CONCLUSIONS: There was no association between total fat intake and the incidence of T2D. However, for specific fats and fatty acids, dose-response curves provided insights for significant associations with T2D. In particular, a high intake of vegetable fat was inversely associated with T2D incidence. Thus, a diet including vegetable fat rather than animal fat might be beneficial regarding T2D prevention.