Improvements in markers of inflammation and coagulation potential following a 5-day high-fat diet rich in cottonseed oil vs. Olive oil in healthy males.

Low-grade inflammation is believed to be a risk factor for chronic diseases and is nutritionally responsive. Cottonseed oil (CSO), which is rich in n-6 polyunsaturated fats, has been shown to lower cholesterol and other chronic disease risk factors. The purpose of this secondary analysis was to determine the comparative responses of markers of inflammation and coagulation potential of healthy adult males consuming diets rich in CSO vs. olive oil (OO). METHODS: Fifteen normal-weight males, ages 21.7 ± 2.58y, completed a randomized crossover trial. Each intervention consisted of a 3-day lead-in diet and a 5-day outpatient, controlled feeding intervention (CSO or OO). There was a 2 to 4-week washout period between interventions. The 5-day intervention diets were 35 % carbohydrate, 15 % protein, and 50 % fat, enriched with either CSO or OO (44 % of total energy from oil). At pre- and post- diet intervention visits, a fasting blood draw was collected for analysis of markers of inflammation (Tumor Necrosis Factor Alpha (TNF-α), Interleukin-6 (IL-6), C-Reactive Protein (CRP)) and coagulation potential (Tissue Factor (TF), Plasminogen Activator Inhibitor-1 (PAI-1)). RESULTS: The CSO-enriched diets reduced TNF-α (CSO: -0.12 ± 0.02 pg/ml, OO: -0.01 ± 0.05 pg/ml; p < 0.01) and TF (CSO: -0.59 ± 0.68 pg/ml, OO: 1.13 ± 0.83 pg/ml; p = 0.02) compared to OO diets. There were no differences in IL-6, CRP, or PAI-1 between diets. CONCLUSION: A 5-day, CSO-enriched diet may be sufficient to reduce inflammation and coagulation potential compared to OO-enriched diets in a healthy male population which could have implications in chronic disease prevention.

Omega-9 monounsaturated fatty acids: a review of current scientific evidence of sources, metabolism, benefits, recommended intake, and edible safety.

Omega-9 monounsaturated fatty acids (ω-9 MUFAs) are a group of unsaturated fatty acids with a unique double bond in the 9th position at the end of the methyl group terminal, having the same double bond location but different carbon chain lengths. Although knowledge about ω-9 MUFAs is constantly being updated, problems with its integration remain in the field. The review summarizes the natural sources, biosynthesis, and catabolic properties of ω-9 MUFAs, emphasizing their positive effects on health functions as well as the active intermediates produced during their metabolic processes. Subsequently, the gap between the actual consumption and recommended intake of ω-9 MUFAs in our daily diet was calculated, and their food safety and potential challenges were discussed. Finally, the outlook of potential future applications and possible research trends are presented. The review aims to promote the rational consumption of ω-9 MUFAs, provide references for their application as functional foods and clinical auxiliary special medical foods, and propose more ideas and possibilities for future scientific research.

Association between dietary fat intake and history of stroke in US adults: findings from National Health and Nutrition Examination Survey 2007-2018.

OBJECTIVES: Diet is an important target for primary prevention of stroke. There are mixed findings on the relationship between dietary fat intake and stroke. We aimed to investigate the relationship of stroke with fats, including total fat, saturated fatty acids (SFA), monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA). METHODS: We analysed data on 27,673 participants who had valid data on dietary fat intake and history of stroke from the National Health and Nutrition Examination Survey 2007-2018. History of stroke was defined according to previous diagnosis by doctors or other health professional. Data on 24-h dietary recalls was collected using Automated Multiple-Pass Method. Age, sex, race/ethnicity, total calories, body mass index, diabetes, hypertension, hypercholesterolaemia, smoking, alcohol consumption and physical activity were adjusted in multivariable models. RESULTS: 3.8% (n = 1,054) of participants had a diagnosis of stroke. History of stroke was inversely associated with total fat (OR = 0.89, 95% CI = 0.79-0.99, P = 0.037), SFA (OR = 0.46, 95% CI = 0.23-0.91) and MUFA (OR = 0.08, 95% CI = 0.02-0.38, P = 0.002) from supplements. There was an inverse association between history of stroke and PUFA intake (from diet: quartile 4 vs quartile 1, OR = 0.58, 95% CI = 0.43-0.78, P for trend = 0.003; from supplements: OR = 0.44, 95% CI = 0.27-0.72, P = 0.001). CONCLUSIONS: In this large-scale nationally representative study, stroke is inversely associated with fat intake from supplements and PUFA intake from diet. While lifestyle choices may not be the most vital health factor for stroke patients, increasing fat intake from specific supplements does provide additional motivation for undertaking the difficult challenge of stroke prevention.

The Role of Neutral Sphingomyelinase-2 (NSM2) in the Control of Neutral Lipid Storage in T Cells.

The accumulation of lipid droplets (LDs) and ceramides (Cer) is linked to non-alcoholic fatty liver disease (NAFLD), regularly co-existing with type 2 diabetes and decreased immune function. Chronic inflammation and increased disease severity in viral infections are the hallmarks of the obesity-related immunopathology. The upregulation of neutral sphingomyelinase-2 (NSM2) has shown to be associated with the pathology of obesity in tissues. Nevertheless, the role of sphingolipids and specifically of NSM2 in the regulation of immune cell response to a fatty acid (FA) rich environment is poorly studied. Here, we identified the presence of the LD marker protein perilipin 3 (PLIN3) in the intracellular nano-environment of NSM2 using the ascorbate peroxidase APEX2-catalyzed proximity-dependent biotin labeling method. In line with this, super-resolution structured illumination microscopy (SIM) shows NSM2 and PLIN3 co-localization in LD organelles in the presence of increased extracellular concentrations of oleic acid (OA). Furthermore, the association of enzymatically active NSM2 with isolated LDs correlates with increased Cer levels in these lipid storage organelles. NSM2 enzymatic activity is not required for NSM2 association with LDs, but negatively affects the LD numbers and cellular accumulation of long-chain unsaturated triacylglycerol (TAG) species. Concurrently, NSM2 expression promotes mitochondrial respiration and fatty acid oxidation (FAO) in response to increased OA levels, thereby shifting cells to a high energetic state. Importantly, endogenous NSM2 activity is crucial for primary human CD4+ T cell survival and proliferation in a FA rich environment. To conclude, our study shows a novel NSM2 intracellular localization to LDs and the role of enzymatically active NSM2 in metabolic response to enhanced FA concentrations in T cells.

Yearly attained adherence to Mediterranean diet and incidence of diabetes in a large randomized trial.

BACKGROUND: Several large observational prospective studies have reported a protection by the traditional Mediterranean diet against type 2 diabetes, but none of them used yearly repeated measures of dietary intake. Repeated measurements of dietary intake are able to improve subject classification and to increase the quality of the assessed relationships in nutritional epidemiology. Beyond observational studies, randomized trials provide stronger causal evidence. In the context of a randomized trial of primary cardiovascular prevention, we assessed type 2 diabetes incidence according to yearly repeated measures of compliance with a nutritional intervention based on the traditional Mediterranean diet. METHODS: PREDIMED (''PREvención con DIeta MEDiterránea'') was a Spanish trial including 7447 men and women at high cardiovascular risk. We assessed 3541 participants initially free of diabetes and originally randomized to 1 of 3 diets: low-fat diet (n = 1147, control group), Mediterranean diet supplemented with extra virgin olive (n = 1154) or Mediterranean diet supplemented with mixed nuts (n = 1240). As exposure we used actual adherence to Mediterranean diet (cumulative average), yearly assessed with the Mediterranean Diet Adherence Screener (scoring 0 to 14 points), and repeated up to 8 times (baseline and 7 consecutive follow-up years). This score was categorized into four groups: < 8, 8-< 10, 10- < 12, and 12-14 points. The outcome was new-onset type 2 diabetes. RESULTS: Multivariable-adjusted hazard ratios from time-varying Cox models were 0.80 (95% confidence interval, 0.70-0.92) per + 2 points in Mediterranean Diet Adherence Screener (linear trend p = .001), and 0.46 (0.25-0.83) for the highest (12-14 points) versus the lowest (< 8) adherence. This inverse association was maintained after additionally adjusting for the randomized arm. Age- and sex-adjusted analysis of a validated plasma metabolomic signature of the Mediterranean Diet Adherence Screener (constituted of 67 metabolites) in a subset of 889 participants also supported these results. CONCLUSIONS: Dietary intervention trials should quantify actual dietary adherence throughout the trial period to enhance the benefits and to assist results interpretation. A rapid dietary assessment tool, yearly repeated as a screener, was able to capture a strong inverse linear relationship between Mediterranean diet and type 2 diabetes. Trial registration ISRCTN35739639.

The effect of PPAR isoform (de)activation on the lipid composition in full-thickness skin models.

Human skin equivalents (HSEs) are 3D-cultured human skin models that mimic many aspects of native human skin (NHS). Although HSEs resemble NHS very closely, the barrier located in the stratum corneum (SC) is impaired. This is caused by an altered lipid composition in the SC of HSEs compared with NHS. One of the most pronounced changes in this lipid composition is a high level of monounsaturation. One key enzyme in this change is stearoyl-CoA desaturase-1 (SCD1), which catalyses the monounsaturation of lipids. In order to normalize the lipid composition, we aimed to target a group of nuclear receptors that are important regulators in the lipid synthesis. This group of receptors are known as the peroxisome proliferating activating receptors (PPARs). By (de)activating each isoform (PPAR-α, PPAR-δ and PPAR-γ), the PPAR isoforms may have normalizing effects on the lipid composition. In addition, another PPAR-α agonist Wy14643 was included as this supplement demonstrated normalizing effects in the lipid composition in a more recent study. After PPAR (ant)agonists supplementation, the mRNA of downstream targets, lipid synthesis genes and lipid composition were investigated. The PPAR downstream targets were activated, indicating that the supplements reached the keratinocytes to trigger their effect. However, minimal impact was observed on the lipid composition after PPAR isoform (de) activation. Only the highest concentration Wy14643 resulted in strong, but negative effects on CER composition. Although the novel tested modifications did not result in an improvement, more insight is gained on the nuclear receptors PPARs and their effects on the lipid barrier in full-thickness skin models.

Metabolomics Biomarkers for Fatty Acid Intake and Biomarker-Calibrated Fatty Acid Associations with Chronic Disease Risk in Postmenopausal Women.

BACKGROUND: A substantial observational literature relating specific fatty acid classes to chronic disease risk may be limited by its reliance on self-reported dietary data. OBJECTIVES: We aimed to develop biomarkers for saturated (SFA), monounsaturated (MUFA), and polyunsaturated (PUFA) fatty acid densities, and to study their associations with cardiovascular disease (CVD), cancer, and type 2 diabetes (T2D) in Women's Health Initiative (WHI) cohorts. METHODS: Biomarker equations were based primarily on serum and urine metabolomics profiles from an embedded WHI human feeding study (n = 153). Calibration equations were based on biomarker values in a WHI nutritional biomarker study (n = 436). Calibrated intakes were assessed in relation to disease incidence in larger WHI cohorts (n = 81,894). Participants were postmenopausal women, aged 50-79 when enrolled at 40 United States Clinical Centers (1993-1998), with a follow-up period of ∼20 y. RESULTS: Biomarker equations meeting criteria were developed for SFA, MUFA, and PUFA densities. That for SFA density depended somewhat weakly on metabolite profiles. On the basis of our metabolomics platforms, biomarkers were insensitive to trans fatty acid intake. Calibration equations meeting criteria were developed for SFA and PUFA density, but not for MUFA density. With or without biomarker calibration, SFA density was associated positively with risk of CVD, cancer, and T2D, but with small hazard ratios, and CVD associations were not statistically significant after controlling for other dietary variables, including trans fatty acid and fiber intake. Following this same control, PUFA density was not significantly associated with CVD risk, but there were positive associations for some cancers and T2D, with or without biomarker calibration. CONCLUSIONS: Higher SFA and PUFA diets were associated with null or somewhat higher risk for clinical outcomes considered in this population of postmenopausal United States women. Further research is needed to develop even stronger biomarkers for these fatty acid densities and their major components. This study is registered with clinicaltrials.gov identifier: NCT00000611.

Low Unsaturated Fatty Acids Level in the Vertebral Bone Marrow of Postmenopausal Osteoporosis: A Pilot 2D iDQC-MRS on 3.0 T Study.

BACKGROUND: Unsaturated fatty acids (UFAs) of bone marrow play a critical role in osteoporosis. However, it is difficult to resolve the UFA, especially in the presence of trabecular bone, using conventional magnetic resonance spectroscopy (MRS) methods. PURPOSE: To preliminarily compare the bone marrow fatty acids (FAs) composition in the presence of trabecular bone of postmenopausal osteoporosis (PMOP) and healthy controls (HC). STUDY TYPE: Prospective. SUBJECTS: Total thirty-six postmenopausal women were recruited with CT-confirmed PMOP (n = 19) and HC (n = 17). FIELD STRENGTH/SEQUENCES: A 3 T scanner. Localized 2D intermolecular double-quantum coherence-based MRS (iDQC-MRS). ASSESSMENT: In addition to the conventional water and fat peaks, another four crossing peaks of the FAs were well resolved from the L4 vertebral bone marrow using iDQC-MRS technique: allylic methylene (2.0 ppm), terminal methylene (2.2 ppm), diallylic methylene (2.7 ppm), and olefinic (5.3 ppm). The monounsaturated fatty acids (MOFA) and polyunsaturated fatty acids (PUFAs) were then calculated. STATISTICAL TESTS: Differences between PMOP and HC were investigated using the analysis of a t-test, and the relationships were investigated using regression analysis. RESULTS: MOFAs and PUFAs fractions were significantly lower in the PMOP group compared to the HC group. In contrast, the saturated FAs fraction is significantly higher in the PMOP group. Additionally, decreased PUFAs, MOFAs were moderately negatively correlated with the volumetric bone mineral density (vBMD) in the PMOP group. Furthermore, increased SFAs in PMOP were strongly associated with vBMD. DATA CONCLUSION: Using spectra resolution enhanced 2D iDQC-MRS technique, we observed low unsaturated FAs levels in the vertebral bone marrow of the PMOP patients. The reduced unsaturated FAs levels in PMOP may be associated with dysfunction of the balance between osteoblastogenesis and osteoclastogenesis. TECHNICAL EFFICACY STAGE: 1.

Novel high-oleic oil consumption for cardiometabolic health: a narrative review.

Several cardiometabolic disorders are risk factors for cardiovascular diseases (CVDs), and prevention is imperative in reducing the burden of these diseases on the healthcare system. Although novel high-oleic acid oils (HOOs) are now commonly used for high-temperature frying in both foodservice and the manufacture of processed foods, there are still limited data regarding their effects on CVD risk. This narrative review aims to clarify these effects by comparing HOOs with saturated fatty acid (SFA)-rich and polyunsaturated fatty acid (PUFA)-rich oils, first regarding their physicochemical properties and then concerning their effects on CVD risk factors using recent randomized controlled trials (RCTs). Overall, although HOOs are more stable than PUFA-rich oils, they do not have the same high-temperature stability as SFA-rich oils. RCTs demonstrate that HOO consumption improves the plasma lipid profile compared with SFA-rich oils while showing similar effects to those of PUFA-rich oils on CVD risk factors. Finally, the current literature lacks information on the actual consumption of HOOs, their long-term effects on cardiometabolic health, and the impact of prolonged heating of these oils on CVD risk factors. In sum, the short-term intake of HOOs may be beneficial for cardiometabolic health; however, more research is needed.

Dietary intake, biomarkers and supplementation of fatty acids and risk of coronary events: a systematic review and dose-response meta-analysis of randomized controlled trials and prospective observational studies.

We aimed to review the association of dietary fats and risk of coronary events in adults. We searched PubMed, Embase, CENTRAL, Scopus, and Web of Sciences to April 2022 for prospective cohorts and randomized trials investigating the association of dietary intake and biomarkers of fats and fatty acid interventions and the risk of coronary events. We performed random-effects meta-analyses to estimate relative risk (RR) for the top versus bottom tertiles of exposures. One-hundered sixty-five prospective cohorts and randomized trials were included. Dietary intake and biomarkers of total fat and saturated, monounsaturated, and polyunsaturated fatty acids were not associated with the risk of coronary events. Dietary intake of trans fatty acids, palmitic acid, stearic acid, and saturated fatty acids from meat and unprocessed meat was modestly associated with a higher risk and, in contrast, intake of alpha-linolenic acid, long-chain omega-3 fatty acids, and linoleic acid was modestly associated with a lower risk. Supplementation with long-chain omega-3 fatty acids and increasing the consumption of alpha-linolenic and linoleic acids in place of saturated fats reduced the risk of coronary events. Existing evidence, in its totality, provides a modest support in favor of current recommendations suggesting replacement of saturated fats with polyunsaturated fats.

Effects of saturated versus unsaturated fatty acids on metabolism, gliosis, and hypothalamic leptin sensitivity in male mice.

BACKGROUND: Development of obesity and its comorbidities is not only the result of excess energy intake, but also of dietary composition. Understanding how hypothalamic metabolic circuits interpret nutritional signals is fundamental to advance towards effective dietary interventions. OBJECTIVE: We aimed to determine the metabolic response to diets enriched in specific fatty acids. METHODS: Male mice received a diet enriched in unsaturated fatty acids (UOLF) or saturated fatty acids (SOLF) for 8 weeks. RESULTS: UOLF and SOLF mice gained more weight and adiposity, but with no difference between these two groups. Circulating leptin levels increased on both fatty acid-enriched diet, but were higher in UOLF mice, as were leptin mRNA levels in visceral adipose tissue. In contrast, serum non-esterified fatty acid levels only rose in SOLF mice. Hypothalamic mRNA levels of NPY decreased and of POMC increased in both UOLF and SOLF mice, but only SOLF mice showed signs of hypothalamic astrogliosis and affectation of central fatty acid metabolism. Exogenous leptin activated STAT3 in the hypothalamus of all groups, but the activation of AKT and mTOR and the decrease in AMPK activation in observed in controls and UOLF mice was not found in SOLF mice. CONCLUSIONS: Diets rich in fatty acids increase body weight and adiposity even if energy intake is not increased, while increased intake of saturated and unsaturated fatty acids differentially modify metabolic parameters that could underlie more long-term comorbidities. Thus, more understanding of how specific nutrients affect metabolism, weight gain, and obesity associated complications is necessary.

Nutritional efficacy of Astaxanthin in modulating orexin peptides and fatty acid level during adult life of rats exposed to perinatal undernutrition stress.

Perinatal undernutrition stress predisposes several disorders in adult life, which could be programed using nutraceuticals. However, the effect of perinatal undernutrition stress on orexin peptides, brain lipids, and its amelioration by a potent antioxidant (Astaxanthin) needs exploration. The present study focussed on the effect of perinatal undernutrition stress on brain fatty acid levels, Orexin peptides A and B, and its amelioration by Astaxanthin.Twenty-four male Wistar rats (Rattus norvegicus) were allocated to four groups (n = 6) as Normal, Perinatally Undernourished (UN), Astaxanthin treated (AsX, 12mg/kg), and perinatally Undernourished-but-Astaxanthin treated (UNA), and are allowed to grow for 1, 6 and 12 months. The fatty acid and orexin peptides A & B at different brain parts were measured and compared. Orexin peptides were assessed using an ELISA kit. Fatty acid levels were estimated using HP 5890 gas chromatograph. Data were analyzed by ANOVA followed by Tukey's posthoc test. P < 0.05 was considered significant.The hair cortisol, Orexin-A, and B were significantly increased (p < 0.001) in the UN group compared to normal and were modulated significantly by AsX in the UNA group. Undernutrition stress during the perinatal period altered the lipid profile, Total SFA, Total MUFA, Total n-3 PUFA, Total n-6 PUFA, n-3: n-6 PUFA, which Astaxanthin effectively modulated at 6 and 12 months of postnatal life. There was no difference between DHA and AA ratio. These results indicate that nutritional enrichment with Astaxanthin during the perinatal period positively contributes to adult health. Further, the mechanism of regulation of brain chemistry by Astaxanthin is warranted.

Relationship between monounsaturated fatty acids and sarcopenia: a systematic review and meta-analysis of observational studies.

Accumulating evidence suggests that fatty acids (FAs) play an essential role in regulating skeletal muscle mass and function throughout life. This systematic review and meta-analysis aimed to examine the relationship between dietary or circulatory levels of monounsaturated FAs (MUFAs) and sarcopenia in observational studies. A comprehensive literature search was performed in three databases (PubMed, Scopus, and Web of Science) from inception until August 2022. Of 414 records, a total of 12 observational studies were identified for this review. Ten studies were meta-analysed, comprising a total of 3704 participants. The results revealed that MUFA intake is inversely associated with sarcopenia (standardized mean difference = - 0.28, 95% CI - 0.46 to - 0.11; p < 0.01). Despite the limited number of studies, our results suggest that lower MUFA intake is associated with a higher risk of sarcopenia. However, the available evidence is still insufficient and further investigations are needed to demonstrate this relationship.

Fatty acid-sensing mechanisms in the hypothalamus of European sea bass (Dicentrarchus labrax): The potential role of monounsaturated and polyunsaturated fatty acids.

This study aimed to evaluate the hypothalamus fatty acid (FA)-sensing mechanisms response to different FA in European sea bass. For that purpose, fish (body weight of 90 g) were intraperitoneally (IP) injected (time 0 h) with five long-chain unsaturated fatty acids, namely, docosahexaenoic acid (DHA; C22:5n3); eicosapentaenoic acid (EPA; C20:4n3); α-linolenic (ALA; C18:3n3); linoleic acid (LA; C18:2n6) and oleic acid (OA; C18:1n9) at a dose of 300 µg kg-1, or with 0.9% saline solution (control). Feed intake (FI) was recorded at 3, 6, and 24 h after the IP injection. One week later, fish were IP injected with the same FA, and the hypothalamus was collected 3 h after the IP injection for measurement of molecules related to FI regulation and FA-sensing mechanisms. Cumulative FI (g/kg/day) was not affected by treatments. However, compared to the control, FI increased with the OA treatment at 6 h after the IP injection. FI decreased with mealtime in the DHA and LA groups. Gene expression of orexigenic (npy/agrp) and anorexigenic (cart2/pomc1) neurons was not affected by the FA treatments. Attending the enzymes involved in the FA-sensing mechanisms activation, compared to the control carnitine palmitoyltransferase I (CPT1) and ATP citrate lyase (ACLY) activity were not affected by FA treatments. Contrarily the key enzymes of lipid metabolisms, malic enzyme and hydroxyacylCoA dehydrogenase was higher in fish that received the EPA and OA treatment, than fish treated to the control. Overall, the results of the present study indicate that gene expression of orexigenic and anorexigenic neurons was not affected at 3 h after IP injection with different FA. However, the activity of key enzymes of lipid metabolism was differently affected by circulating FA, indicating that FA-sensing mechanisms respond to different FA. Further studies are required involving different sampling times to further characterize the response of FA-sensing mechanisms to FA. These findings may be of relevance to the aquaculture industry in an era where alternative lipid sources are being increasingly used.

Carcass traits, proximate composition, amino acid and fatty acid profiles, and mineral contents of meat from Cherry Valley, Chinese crested, and crossbred ducks.

Duck meat is known for its taste and high nutritive value. To preserve local genetic diversity while maintaining commercial viability, we obtained a crossbreed (CB) between high-performing Cherry Valley (CV) and traditional Chinese crested (CC) ducks. We compared carcass traits and meat quality characteristics of CB and parental breeds. Meat from the above ducks at their respective marketable ages was evaluated for proximate composition, amino acid and fatty acid profiles, and selected mineral content. The live weights, carcass weights, and breast muscle percentage of CB were higher than CC but lower than CV; the leg muscle of CB was lower than CV and CC. CB had higher intramuscular fat content than CV; its collagen content was lower than CC but higher than CV in breast and thigh muscles. Additionally, the saturated fatty acid content of CB muscle was lower than CV and higher than CC. CB contained more monounsaturated fatty acids than CV and CC. Zn content was higher in CB breast than CV and CC. CB, obtained by crossing CV and CC, has partial advantages over both the breeds suggesting that these characteristics aligned with standards to breed ducks with high-quality meat.

Unveiling the MUFA-Cancer Connection: Insights from Endogenous and Exogenous Perspectives.

Monounsaturated fatty acids (MUFAs) have been the subject of extensive research in the field of cancer due to their potential role in its prevention and treatment. MUFAs can be consumed through the diet or endogenously biosynthesized. Stearoyl-CoA desaturases (SCDs) are key enzymes involved in the endogenous synthesis of MUFAs, and their expression and activity have been found to be increased in various types of cancer. In addition, diets rich in MUFAs have been associated with cancer risk in epidemiological studies for certain types of carcinomas. This review provides an overview of the state-of-the-art literature on the associations between MUFA metabolism and cancer development and progression from human, animal, and cellular studies. We discuss the impact of MUFAs on cancer development, including their effects on cancer cell growth, migration, survival, and cell signaling pathways, to provide new insights on the role of MUFAs in cancer biology.

Role of Stearoyl-CoA Desaturase 1 in Cardiovascular Physiology.

Stearoyl-CoA desaturase is a rate-limiting enzyme in the synthesis of monounsaturated fatty acids. Monounsaturated fatty acids limit the toxicity of exogenous saturated fats. Studies have shown that stearoyl-CoA desaturase 1 is involved in the remodeling of cardiac metabolism. The loss of stearoyl-CoA desaturase 1 reduces fatty acid oxidation and increases glucose oxidation in the heart. Such a change is protective under conditions of a high-fat diet, which reduces reactive oxygen species-generating ß-oxidation. In contrast, stearoyl-CoA desaturase 1 deficiency predisposes individuals to atherosclerosis under conditions of hyperlipidemia but protects against apnea-induced atherosclerosis. Stearoyl-CoA desaturase 1 deficiency also impairs angiogenesis after myocardial infarction. Clinical data show a positive correlation between blood stearoyl-CoA Δ-9 desaturation rates and cardiovascular disease and mortality. Moreover, stearoyl-CoA desaturase inhibition is considered an attractive intervention in some obesity-associated pathologies, and the importance of stearoyl-CoA desaturase in the cardiovascular system might be a limitation for developing such therapy. This review discusses the role of stearoyl-CoA desaturase 1 in the regulation of cardiovascular homeostasis and the development of heart disease and presents markers of systemic stearoyl-CoA desaturase activity and their predictive potential in the diagnosis of cardiovascular disorders.

Dietary palmitate and oleate differently modulate insulin sensitivity in human skeletal muscle.

AIMS/HYPOTHESIS: Energy-dense nutrition generally induces insulin resistance, but dietary composition may differently affect glucose metabolism. This study investigated initial effects of monounsaturated vs saturated lipid meals on basal and insulin-stimulated myocellular glucose metabolism and insulin signalling. METHODS: In a randomised crossover study, 16 lean metabolically healthy volunteers received single meals containing safflower oil (SAF), palm oil (PAL) or vehicle (VCL). Whole-body glucose metabolism was assessed from glucose disposal (Rd) before and during hyperinsulinaemic-euglycaemic clamps with D-[6,6-2H2]glucose. In serial skeletal muscle biopsies, subcellular lipid metabolites and insulin signalling were measured before and after meals. RESULTS: SAF and PAL raised plasma oleate, but only PAL significantly increased plasma palmitate concentrations. SAF and PAL increased myocellular diacylglycerol and activated protein kinase C (PKC) isoform θ (p < 0.05) but only PAL activated PKCɛ. Moreover, PAL led to increased myocellular ceramides along with stimulated PKCζ translocation (p < 0.05 vs SAF). During clamp, SAF and PAL both decreased insulin-stimulated Rd (p < 0.05 vs VCL), but non-oxidative glucose disposal was lower after PAL compared with SAF (p < 0.05). Muscle serine1101-phosphorylation of IRS-1 was increased upon SAF and PAL consumption (p < 0.05), whereas PAL decreased serine473-phosphorylation of Akt more than SAF (p < 0.05). CONCLUSIONS/INTERPRETATION: Lipid-induced myocellular insulin resistance is likely more pronounced with palmitate than with oleate and is associated with PKC isoforms activation and inhibitory insulin signalling. TRIAL REGISTRATION: ClinicalTrials.gov .NCT01736202. FUNDING: German Federal Ministry of Health, Ministry of Culture and Science of the State North Rhine-Westphalia, German Federal Ministry of Education and Research, European Regional Development Fund, German Research Foundation, German Center for Diabetes Research.

Altered Plasma Fatty Acids Associate with Gut Microbial Composition in Common Variable Immunodeficiency.

PURPOSE: Fatty acid (FA) abnormalities are found in various inflammatory disorders and have been related to disturbed gut microbiota. Patients with common variable immunodeficiency (CVID) have inflammatory complications associated with altered gut microbial composition. We hypothesized that there is an altered FA profile in CVID patients, related to gut microbial dysbiosis. METHODS: Plasma FAs were measured in 39 CVID patients and 30 healthy controls. Gut microbial profile, a food frequency questionnaire, and the effect of the oral antibiotic rifaximin were investigated in CVID patients. RESULTS: The n-3 polyunsaturated fatty acids (PUFAs), eicosapentaenoic acid (EPA) (1.4 [1.0-1.8] vs. 1.9 [1.2-2.5], median (IQR), P < 0.05), and docosahexaenoic acid (DHA) (3.2 [2.4-3.9] vs. 3.5 [2.9-4.3], P < 0.05), all values expressed as weight percent of total plasma FAs, were reduced in CVID compared to controls. Also, n-6 PUFAs (34.3 ± 3.4 vs. 37.1 ± 2.8, mean ± SD, P < 0.001) and linoleic acid (LA) (24.5 ± 3.3 vs. 28.1 ± 2.7, P < 0.0001) and the FA anti-inflammatory index (98.9 [82.1-119.4] vs. 117.0 [88.7-153.1], median (IQR), P < 0.05) were reduced in CVID. The microbial alpha diversity was positively associated with plasma n-6 PUFAs (r = 0.41, P < 0.001) and LA (r = 0.51, P < 0.001), but not n-3 PUFAs (P = 0.78). Moreover, a 2-week course of rifaximin significantly reduced the proportion of n-6 PUFAs (P = 0.04, UNIANOVA). Serum immunoglobulin G (IgG) levels correlated with plasma n-3 PUFAs (rho = 0.36, P = 0.03) and DHA (rho = 0.41, P = 0.009). CONCLUSION: We found a potentially unfavorable FA profile in CVID, related to low IgG levels. High plasma n-6 PUFAs were related to increased gut microbial diversity and altered by rifaximin therapy.

Peri-tumoural spatial distribution of lipid composition and tubule formation in breast cancer.

BACKGROUND: Response guided treatment in breast cancer is highly desirable, but the effectiveness is only established based on residual cellularity from histopathological analysis after surgery. Tubule formation, a key component of grading score, is directly associated with cellularity, with significant implications on prognosis. Peri-tumoural lipid composition, a potential marker, can be rapidly mapped across the entire breast using novel method of chemical shift-encoded imaging, enabling the quantification of spatial distribution. We hypothesise that peri-tumoural spatial distribution of lipid composition is sensitive to tumour cellular differentiation and proliferative activity. METHODS: Twenty whole tumour specimens freshly excised from patients with invasive ductal carcinoma (9 Score 2 and 11 Score 3 in tubule formation) were scanned on a 3 T clinical scanner (Achieva TX, Philips Healthcare). Quantitative lipid composition maps were acquired for polyunsaturated, monounsaturated, and saturated fatty acids (PUFA, MUFA, SFA). The peri-tumoural spatial distribution (mean, skewness, entropy and kurtosis) of each lipid constituent were then computed. The proliferative activity marker Ki-67 and tumour-infiltrating lymphocytes (TILs) were assessed histologically. RESULTS: For MUFA, there were significant differences between groups in mean (p = 0.0119), skewness (p = 0.0116), entropy (p = 0.0223), kurtosis (p = 0.0381), and correlations against Ki-67 in mean (ρ = -0.5414), skewness (ρ = 0.6045) and entropy (ρ = 0.6677), and TILs in mean (ρ = -0.4621). For SFA, there were significant differences between groups in mean (p = 0.0329) and skewness (p = 0.0111), and correlation against Ki-67 in mean (ρ = 0.5910). For PUFA, there was no significant difference in mean, skewness, entropy or kurtosis between the groups. CONCLUSIONS: There was an association between peri-tumoural spatial distribution of lipid composition with tumour cellular differentiation and proliferation. Peri-tumoural lipid composition imaging might have potential in non-invasive quantitative assessment of patients with breast cancer for treatment planning and monitoring.