MUFA-rich Diet Research Articles

Abstract PR-06: Dietary fats dictate pancreatic cancer fate via phospholipid saturation

Abstract Pancreatic ductal adenocarcinoma (PDAC) is the third leading cause of cancer death in the US and is anticipated to become the second within the next decade. Epidemiologic studies support a strong link between high fat diet (HFD) consumption and increased PDAC risk, however, the translational relevance of diet research has been limited by inconsistencies in fat source and consumption across human populations and mouse studies. Therefore, whether and how specific dietary fatty acids drive cancer development is poorly understood. To address this gap in knowledge, we performed a diet screen, comprised of 12 isocaloric HFDs differing solely in fat source and representing the diversity of modern human fat consumption, in an oncogenic Kras-driven mouse model (KC: Kras LSL-G12D /+;Pdx1-Cre) that closely mimics the genetic and histologic features of human PDAC progression. Unexpectedly, we discovered that diets rich in oleic acid – a monounsaturated fatty acid (MUFA) typically associated with good health – enhanced pancreatic tumorigenesis. Furthermore, we observed a strong positive correlation between increased tumor burden and diets exhibiting a high ratio of MUFAs to polyunsaturated fatty acids (PUFAs), concordant with high MUFA to PUFA levels in the plasma and in pancreatic phospholipids. Membrane phospholipid incorporation of MUFAs (relative to PUFAs) suppresses lipid peroxidation and cell death via ferroptosis. Consistent with this, pancreata from mice fed a MUFA-rich diet showed decreased expression of genes involved in lipid peroxidation and reduced histologic evidence of lipid peroxidation end products compared to a PUFA-rich diets. Furthermore, primary acinar cells from mice fed high MUFA diets were resistant to cell death upon treatment with ferroptosis inhibitors. Conversely, diets rich in PUFAs increased PUFA incorporation into pancreatic phospholipids, activated transcriptional programs of lipid peroxidation, and intercepted Kras-driven tumor progression in vivo. Collectively, these data support a role for dietary fatty acids in molding the pancreatic phospholipid landscape, altering lipid peroxidation and ferroptosis sensitivity to dictate tumor fate. Citation Format: Christian F Ruiz, Xiangyu Ge, Rylee McDonnell, Daniel McQuaid, Jennifer Kaplan, Guangtao Li, Michael C Rudolph, Fred F Gorelick, John Wysolmerski, Daniel Canals, John D Haley, Matthew Rodeheffer, Mandar D Muzumdar. Dietary fats dictate pancreatic cancer fate via phospholipid saturation [abstract]. In: Proceedings of the AACR Special Conference in Cancer Research: Advances in Pancreatic Cancer Research; 2024 Sep 15-18; Boston, MA. Philadelphia (PA): AACR; Cancer Res 2024;84(17 Suppl_2):Abstract nr PR-06.

Differential Effects of Two Isocaloric Healthy Diets on Postprandial Lipid Responses in Individuals with Type 2 Diabetes.

High blood concentrations of triglycerides (TG) in the postprandial period have been shown to be more closely associated with the risk of cardiovascular disease (CVD) than fasting values in individuals with type 2 diabetes (T2D). Dietary changes are the primary determinants of postprandial lipid responses. We investigated the effects of an isocaloric multifactorial diet, rich in n-3 PUFA, MUFA, fiber, polyphenols, and vitamins, compared to an isocaloric diet, containing the same amount of MUFA, on the postprandial lipid response in T2D individuals. Following a randomized, controlled, parallel group design, 43 (25 male/18 female) T2D individuals were assigned to an isocaloric multifactorial (n = 21) or a MUFA-rich diet (n = 22). At the beginning and after the 8 weeks of dietary intervention, the concentrations of plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol were detected at fasting and over a 4-h test meal with the same composition as the prescribed diet. The concentrations of fasting plasma triglycerides, total cholesterol, HDL cholesterol, and non-HDL cholesterol did not change after both diets. Compared with the MUFA diet, the 8-week multifactorial diet significantly lowered the postprandial response, which was evaluated as the incremental area under the curve (iAUC), of triglycerides by 33% (64 ± 68 vs. 96 ± 50 mmol/L·240 min, mean ± SD, respectively, p = 0.018), total cholesterol by 105% (-51 ± 33 vs. -25 ± 29, p = 0.013), and non-HDL cholesterol by 206% (-39 ± 33 vs. -13 ± 23, p = 0.013). In T2D individuals, a multifactorial diet, characterized by several beneficial components, improved the postprandial lipid response compared to a MUFA diet, generally considered a healthy diet being reduced in saturated fat, and probably contributed to the reduction of cardiovascular risk.

Effects of diets rich in monounsaturated fatty acids on the management and prevention of insulin resistance: A systematic review

Insulin resistance (IR), which is linked to obesity, is a mechanism associated with metabolic diseases, mainly type 2 diabetes mellitus. Studies have shown that monounsaturated fatty acids (MUFAs) have anti-inflammatory and anti-oxidative properties which positively affect IR. This systematic review examined the effects of MUFAs from different sources on IR in obese or overweight patients with or without metabolic syndrome. A search was carried out in the PubMed/Medline and Bireme/VHL databases, and data from 16 studies were analysed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines. The intervention time ranged from 1 day to 5.2 years. All participants were overweight or obese; some had central obesity, a moderate risk of cardiovascular disease, low high-density lipoprotein levels, altered fasting glucose levels, prediabetes or type 2 diabetes mellitus. This systematic review provides evidence that MUFA-rich diets can improve IR.

An Isoenergetic Multifactorial Diet Reduces Pancreatic Fat and Increases Postprandial Insulin Response in Patients With Type 2 Diabetes: A Randomized Controlled Trial.

To compare the effect of an isocaloric multifactorial diet with a diet rich in monounsaturated fatty acids (MUFA) and similar macronutrient composition on pancreatic fat (PF) and postprandial insulin response in type 2 diabetes (T2D). According to a randomized controlled parallel-group design, 39 individuals with T2D, 35-75 years old, in satisfactory blood glucose control, were assigned to an 8 week isocaloric intervention with a multifactorial diet rich in MUFA, polyunsaturated fatty acids, fiber, polyphenols, and vitamins (n = 18) or a MUFA-rich diet (n = 21). Before/after the intervention, PF content was measured by the proton-density fat fraction using a three-dimensional mDIXON MRI sequence, and plasma insulin and glucose concentrations were measured over a 4 h test meal with a similar composition as the assigned diet. After 8 weeks, PF significantly decreased after the multifactorial diet (from 15.7 ± 6.5% to 14.1 ± 6.3%; P = 0.024), while it did not change after the MUFA diet (from 17.1 ± 10.1% to 18.6 ± 10.6%; P = 0.139) with a significant difference between diets (P = 0.014). Postprandial glucose response was similar in the two groups. Early postprandial insulin response (incremental postprandial areas under the curve [iAUC0-120]) significantly increased with the multifactorial diet (from 36,340 ± 34,954 to 44,138 ± 31,878 pmol/L/min; P = 0.037), while it did not change significantly in the MUFA diet (from 31,754 ± 18,446 to 26,976 ± 12,265 pmol/L/min; P = 0.178), with a significant difference between diets (P = 0.023). Changes in PF inversely correlated with changes in early postprandial insulin response (r = -0.383; P = 0.023). In patients with T2D, an isocaloric multifactorial diet, including several beneficial dietary components, markedly reduced PF. This reduction was associated with an improved postprandial insulin response.

Reduction of De Novo Lipogenesis Mediates Beneficial Effects of Isoenergetic Diets on Fatty Liver: Mechanistic Insights from the MEDEA Randomized Clinical Trial.

Background: Non-alcoholic liver steatosis (NAS) results from an imbalance between hepatic lipid storage, disposal, and partitioning. A multifactorial diet high in fiber, monounsaturated fatty acids (MUFAs), n-6 and n-3 polyunsaturated fatty acids (PUFAs), polyphenols, and vitamins D, E, and C reduces NAS in people with type 2 diabetes (T2D) by 40% compared to a MUFA-rich diet. We evaluated whether dietary effects on NAS are mediated by changes in hepatic de novo lipogenesis (DNL), stearoyl-CoA desaturase (SCD1) activity, and/or β-oxidation. Methods: According to a randomized parallel group study design, 37 individuals with T2D completed an 8-week isocaloric intervention with a MUFA diet (n = 20) or multifactorial diet (n = 17). Before and after the intervention, liver fat content was evaluated by proton magnetic resonance spectroscopy, serum triglyceride fatty acid concentrations measured by gas chromatography, plasma β-hydroxybutyrate by enzymatic method, and DNL and SCD-1 activity assessed by calculating the palmitic acid/linoleic acid (C16:0/C18:2 n6) and palmitoleic acid/palmitic acid (C16:1/C16:0) ratios, respectively. Results: Compared to baseline, mean ± SD DNL significantly decreased after the multifactorial diet (2.2 ± 0.8 vs. 1.5 ± 0.5, p = 0.0001) but did not change after the MUFA diet (1.9 ± 1.1 vs. 1.9 ± 0.9, p = 0.949), with a significant difference between the two interventions (p = 0.004). The mean SCD-1 activity also decreased after the multifactorial diet (0.13 ± 0.05 vs. 0.10 ± 0.03; p = 0.001), but with no significant difference between interventions (p = 0.205). Fasting plasma β-hydroxybutyrate concentrations did not change significantly after the MUFA or multifactorial diet. Changes in the DNL index significantly and positively correlated with changes in liver fat (r = 0.426; p = 0.009). Conclusions: A diet rich in multiple beneficial dietary components (fiber, polyphenols, MUFAs, PUFAs, and other antioxidants) compared to a diet rich only in MUFAs further reduces liver fat accumulation through the inhibition of DNL. Registered under ClinicalTrials.gov no. NCT03380416.

Palmitic Acid and Oleic Acid Differently Modulate TLR2-Mediated Inflammatory Responses in Microglia and Macrophages

The relationship between systemic immunity and neuroinflammation is widely recognised. Infiltration of peripheral immune cells to the CNS during certain chronic inflammatory states contributes significantly to neuropathology. Obesity and its co-morbidities are primary risk factors for neuroinflammatory and neurodegenerative conditions, including Alzheimer’s disease (AD). Dietary fats are among the most proinflammatory components of the obesogenic diet and play a prominent role in the low-grade systemic inflammation associated with the obese state. Saturated fatty acid (SFA) is largely implicated in the negative consequences of obesity, while the health benefits of monounsaturated fatty acid (MUFA) are widely acknowledged. The current study sought to explore whether SFA and MUFA differently modulate inflammatory responses in the brain, compared with peripheral immune cells. Moreover, we assessed the neuroinflammatory impact of high-fat-induced obesity and hypothesised that a MUFA-rich diet might mitigate inflammation despite obesogenic conditions. Toll-like receptor (TLR)2 mediates the inflammation associated with both obesity and AD. Using the TLR2 agonist lipoteichoic acid (LTA), we report that pre-exposure to either palmitic acid (PA) or oleic acid (OA) attenuated cytokine secretion from microglia, but heightened sensitivity to nitric oxide (NO) production. The reduction in cytokine secretion was mirrored in LTA-stimulated macrophages following exposure to PA only, while effects on NO were restricted to OA, highlighting important cell-specific differences. An obesogenic diet over 12 weeks did not induce prominent inflammatory changes in either cortex or hippocampus, irrespective of fat composition. However, we reveal a clear disparity in the effects of MUFA under obesogenic and non-obesogenic conditions.

Monounsaturated fatty acid antagonizes saturated fatty acid-induced cardiomyopathy via improving membrane fatty acid composition and endoplasmic reticulum stress

Abstract Background Obesity-induced lipotoxicity causes cardiac dysfunction in our modern lifestyle. Previously, we have shown that an increase in cardiomyocyte membrane saturated fatty acid (SFA)/ monounsaturated FA (MUFA) ratio mediates endoplasmic reticulum (ER) stress, which was implicated in the pathogenesis of SFA-induced cardiomyopathy. Furthermore, SFA supressed Sirt1/ stearoyl-CoA desaturase-1 (SCD1, converting enzyme from SFA to MUFA) signaling, which further worsened the membrane SFA/MUFA ratio. Purpose To evaluate the effectiveness of targeting membrane fatty acid composition by MUFA. Methods and results In wild-type mice, 16-weeks SFA-rich high lard diet feeding (HLD) caused activation of PPARα signaling and the accumulation of toxic lipid intermediates (diacylglycerol and ceramide) in the heart to the same extent as a MUFA-rich high olive oil diet feeding (HOD). However, only the HLD impaired Sirt1 activity, SCD1 expression, diastolic function (increased left ventricular end-diastolic pressure (LVEDP) and end-diastolic pressure-volume relationship (EDPVR)), and cardiac remodeling (hypertrophy and fibrosis). Lipidome analysis showed that HLD-induced diastolic dysfunction coincided with an increase in membrane SFA/MUFA ratio and ER stress induction. 8-weeks HOD after 8-weeks HLD (HOD switch) showed the same degree of obesity and PPARα activation with 16-weeks HLD. By contrast, HOD switched heart were less severe Sirt1/SCD1 signaling dysregulation, increased in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy (hypertrophy, fibrosis, and diastolic dysfunction) compared to 16-weeks HLD. Moreover, in cardiomyocyte-specific Sirt1 knockout mice, HOD switched heart also showed less severe increase in membrane SFA/MUFA ratio, ER stress, and cardiomyopathy compared to 16-weeks HLD although decreased SCD1 expression was not changed. Conclusions We demonstrated that MUFA-rich diet counteracted SFA-induced Sirt1/SCD1 signaling dysregulation and prevented SFA-induced increase in membrane SFA/MUFA ratio. Hence, MUFA-rich diet antagonized SFA-induced ER stress and cardiomyopathy even if Sirt1 deactivated heart (e.g., aged heart). Targeting the cardiomyocyte membrane SFA/MUFA ratio by MUFA might have a new therapeutic potential for SFA-induced cardiomyopathy. Funding Acknowledgement Type of funding sources: Public Institution(s). Main funding source(s): JSPS KAKENHI

Saturated fatty acid-induced cardiomyopathy with diastolic dysfunction can be ameliorated by changing the quality of fatty acids to monounsaturated fatty acid

IntroductionLipotoxicity due to obesity is known to lead to cardiac dysfunction. In an earlier study, we found that an increase in the ratio of saturated fatty acids (SFA) to monounsaturated fatty acids (MUFA) in the membrane of cardiomyocytes causes endoplasmic reticulum (ER) stress. Such stress is hypothesized to be involved in development of SFA-related cardiomyopathy. Another factor affecting the membrane SFA/MUFA ratio is suppression by SFA of SIRT1-mediated stearoyl-CoA desaturase-1 (SCD1), which is involved in converting SFA to MUFA. Therefore, we evaluated whether increasing dietary intake of MUFA can improve the membrane SFA/MUFA ratio.Material and methodsWild-type mice (n = 30) and cardiomyocyte-specific SIRT1 knockout mice (n = 30) were randomly divided into 3 groups and assigned to 16 weeks of a standard mouse diet, 16 weeks of an SFA-rich high-lard diet (HLD), or 8 weeks of a HLD followed by 8 weeks of a MUFA-rich high olive oil diet (HOD switch).ResultsCompared with the control group, the wild-type mice on the HOD diet showed normalized SIRT1-mediated SCD1 signaling, increased membrane SFA/MUFA ratio, decreased ER stress, and improved cardiomyopathy variables. The HLD-fed SIRT1 knockout mice showed greater changes in the SFA/MUFA ratio, ER stress, and cardiomyopathy variables than the wild-type mice. Switching from HLD to HOD ameliorated these phenotypes, although it did not restore the reduced expression of SCD1.ConclusionsThe MUFA-rich diet was found to have a therapeutic effect on SFA-induced cardiomyopathy with diastolic dysfunction by directly rebalancing membrane fatty acid oversaturation and indirectly through the de-inhibition of SIRT1/SCD1 signaling.

Appetite responses to high-fat diets rich in mono-unsaturated versus poly-unsaturated fats

BackgroundModifying the type of dietary fat consumed may impact appetite, therefore having implications in weight management. ObjectiveTo test the effects of a 5-day, high-fat diet rich in poly-unsaturated fatty acids (PUFAs) and a diet rich in mono-unsaturated fatty acids (MUFAs) on markers of appetite. MethodsFifteen normal weight men participated in a randomized cross-over design with two controlled feeding trials (3d lead-in diet, pre-diet visit, 5d PUFA- or MUFA-rich diet, post-diet visit). The 5d diets (50% fat) were rich in either PUFA (25% of energy) or MUFA (25% of energy). At pre- and post-diet visits, subjects consumed breakfast and lunch test meals, rich in the FA corresponding to the 5-day diet. Fasting and postprandial subjective ratings of appetite were determined and blood draws were performed for 4h after each meal to determine changes in appetite hormones. An ad libitum buffet meal was given at the end of pre- and post-diet visits. ResultsAcutely, at the pre-diet visit, the PUFA-rich meal resulted in lower ghrelin (hunger hormone) (iAUC: -350.85 ± 60.70 vs. −233.16 ± 61.42 pg/ml/8h, for PUFA vs. MUFA, respectively; p < 0.05) and higher CCK (satiation hormone) (iAUC: 238.09 ± 46.07 vs. 196.84 ± 33.92 pM/8h, for PUFA vs. MUFA, respectively; p < 0.05). No other acute meal challenge differences were found. The 5d high PUFA diet resulted in lower hunger ratings (iAUC: -172.06 ± 40.59 vs. −274.46 ± 41.47 mm/8h, for pre-to post-diet, respectively; p < 0.05). However, energy intake, ratings of fullness, or PYY did not change from pre-to post-diet for either MUFA or PUFA, and no other changes were observed with the MUFA diet. ConclusionsAcutely, a PUFA-rich meal results in ghrelin suppression and higher CCK. After a 5-day high-fat diet, PUFAs suppressed postprandial hunger while MUFAs did not change any measures of appetite.

Metabolic responses to high-fat diets rich in MUFA v. PUFA.

Dietary fatty acid (FA) composition may influence metabolism, possibly affecting weight management. The purpose of this study was to compare the effects of a 5-d diet rich in PUFA v. MUFA. A total of fifteen normal-weight men participated in a randomised cross-over design with two feeding trials (3 d lead-in diet, pre-diet visit, 5-d PUFA- or MUFA-rich diet, post-diet visit). The 5-d diets (50 % fat) were rich in either PUFA (25 % of energy) or MUFA (25 % of energy). At pre- and post-diet visits, subjects consumed breakfast and lunch test meals, rich in the FA for that 5-d diet. Indirect calorimetry was used for 4 h after each meal. There were no treatment differences in fasting metabolism acutely or after the 5-d diet. For acute meal responses before diet, RER was higher for PUFA v. MUFA (0·86 (sem 0·01) v. 0·84 (sem 0·01), P<0·05), whereas diet-induced thermogenesis (DIT) was lower for PUFA v. MUFA (18·91 (SEM 1·46) v. 21·46 (SEM 1·34) kJ, P<0·05). After the 5-d diets, the change in RER was different for PUFA v. MUFA (-0·02 (sem 0·01) v. 0·00 (sem 0·01), P<0·05). Similarly, the change in fat oxidation was greater for PUFA v. MUFA (0·18 (sem 0·07) v. 0·04 (sem 0·06) g, P<0·05). In conclusion, acutely, a MUFA-rich meal results in lower RER and greater DIT. However, after a 5-d high-fat diet, the change in metabolic responses was greater in the PUFA diet, showing the metabolic adaptability of a PUFA-rich diet.

Replacement of dietary saturated fat with unsaturated fats increases numbers of circulating endothelial progenitor cells and decreases numbers of microparticles: findings from the randomized, controlled Dietary Intervention and VAScular function (DIVAS) study

Endothelial progenitor cells (EPCs) and microparticles are emerging as novel markers of cardiovascular disease (CVD) risk, which could potentially be modified by dietary fat. We have previously shown that replacing dietary saturated fatty acids (SFAs) with monounsaturated or n-6 (ω-6) polyunsaturated fatty acids (MUFAs or PUFAs, respectively) improved lipid biomarkers, blood pressure, and markers of endothelial activation, but their effects on circulating EPCs and microparticles are unclear. The Dietary Intervention and VAScular function (DIVAS) Study investigated the replacement of 9.5-9.6% of total energy (%TE) contributed by SFAs with MUFAs or n-6 PUFAs for 16 wk on EPC and microparticle numbers in United Kingdom adults with moderate CVD risk. In this randomized, controlled, single-blind, parallel-group dietary intervention, men and women aged 21-60 y (n=190) with moderate CVD risk (≥50% above the population mean) consumed 1 of three 16-wk isoenergetic diets. Target compositions for total fat, SFAs, MUFAs, and n-6 PUFAs (%TE) were as follows: SFA-rich diet (36:17:11:4; n=64), MUFA-rich diet (36:9:19:4; n=62), and n-6 PUFA-rich diet (36:9:13:10; n=66). Circulating EPC, endothelial microparticle (EMP), and platelet microparticle (PMP) numbers were analyzed by flow cytometry. Dietary intake, vascular function, and other cardiometabolic risk factors were determined at baseline. Relative to the SFA-rich diet, MUFA- and n-6 PUFA-rich diets decreased EMP (-47.3%, -44.9%) respectively and PMP (-36.8%, -39.1%) numbers (overall diet effects, P<0.01). The MUFA-rich diet increased EPC numbers (+28.4%; P=0.023). Additional analyses that used stepwise regression models identified the augmentation index (measuring arterial stiffness determined by pulse-wave analysis) as an independent predictor of baseline EPC and microparticle numbers. Replacement of 9.5-9.6%TE dietary SFAs with MUFAs increased EPC numbers, and replacement with either MUFAs or n-6 PUFAs decreased microparticle numbers, suggesting beneficial effects on endothelial repair and maintenance. Further studies are warranted to determine the mechanisms underlying the favorable effects on EPC and microparticle numbers after SFA replacement. This trial was registered at www.clinicaltrials.gov as NCT01478958.

Health benefits and evaluation of healthcare cost savings if oils rich in monounsaturated fatty acids were substituted for conventional dietary oils in the United States.

The impact of nutritional behaviors on health is beyond debate and has the potential to affect the economic outputs of societies in significant ways. Dietary fatty acids have become a central theme in nutrition research in recent years, and the popularity of dietary oils rich in healthy fatty acids, such as monounsaturated fatty acid (MUFA), for cooking applications and use in food products has increased. Here, the objective is to summarize the health effects of MUFA-rich diets and to systematically estimate the potential healthcare and societal cost savings that could be realized by increasing MUFA intakes compared with other dietary fat intakes in the United States. Using a scoping review approach, the literature of randomized controlled clinical trials was searched and a 4-step cost-of-illness analysis was developed, which included estimates of success rate, disease biomarker reduction, disease incidence reduction, and cost savings. Findings revealed improvements in established biomarkers and in incidence of coronary heart disease and type 2 diabetes, along with potentially substantial annual healthcare and societal cost savings when recommendations for daily MUFA intake were followed. In summary, beyond the beneficial health effects of MUFA-rich diets, potential economic benefits suggest practical implications for consumers, food processors, and healthcare authorities alike.

A high-MUFA diet alone does not affect ketone body metabolism, but reduces glycated hemoglobin when combined with exercise training in diabetic rats

Abstract Background Monounsaturated fat (MUFA) also has glucose-lowering action, but its effect on ketone bodies is unknown. Objectives To examine the effects of high-MUFA diet alone or in combination with exercise training, which can improve glucose and ketone body metabolism, in a rat model of diabetes. Methods Wistar rats were administered streptozotocin to induce diabetes and then randomly divided into five groups: sedentary rats fed a regular diet (1), a high-saturated-fat diet (2), a high-MUFA diet (3); and exercisetrained rats fed a regular diet (4), and a high-MUFA diet (5). Training was by a treadmill twice daily, 5 days/week. At 12 weeks, glucose, glycated hemoglobin (HbA1c), insulin, nonesterified fatty acids (NEFA), and β-hydroxybutyrate levels were measured in cardiac blood. Activity of the overall ketone synthesis pathway was determined in liver and 3-ketoacyl-CoA transferase activity determined in gastrocnemius muscle. Results A high-MUFA diet tended to lower plasma glucose without affecting other biochemical variables. Training did not change glucose metabolism, but significantly reduced serum NEFA. Only the high-MUFA diet plus training significantly decreased HbA1c levels. Hepatic ketone synthesis was decreased and 3-ketoacyl-CoA transferase activity was increased by training alone or in combination with a high-MUFA diet. Changes in NEFA, β-hydroxybutyrate, and the enzymatic activities in response to training plus a high-MUFA diet were comparable to those caused by training alone. Conclusion A high-MUFA diet alone does not alter ketone body metabolism. Combination of a MUFA-rich diet and exercise training is more effective than either MUFA or exercise alone for lowering HbA1c.

Interactions between Obesity Status and Dietary Intake of Monounsaturated and Polyunsaturated Oils on Human Gut Microbiome Profiles in the Canola Oil Multicenter Intervention Trial (COMIT).

Long-term dietary fatty acid intake is believed to induce changes in the human gut microbiome which might be associated with human health or obesity status; however, considerable debate remains regarding the most favorable ratios of fatty acids to optimize these processes. The objective of this sub-study of a double-blinded randomized crossover clinical study, the canola oil multi-center intervention trial, was to investigate effects of five different novel oil blends fed for 30 days each on the intestinal microbiota in 25 volunteers with risk of metabolic syndrome. The 60 g treatments included three MUFA-rich diets: (1) conventional canola oil (Canola); (2) DHA-enriched high oleic canola oil (CanolaDHA); (3) high oleic canola oil (CanolaOleic); and two PUFA-rich diets: (4) a blend of corn/safflower oil (25:75) (CornSaff); and (5) a blend of flax/safflower oil (60:40) (FlaxSaff). Stool samples were collected at the end of each period. DNA was extracted and amplified for 16S rRNA gene pyrosequencing. A total of 17 phyla and 187 genera were identified. While five novel oil treatments failed to alter bacterial phyla composition, obese participants resulted in a higher proportion of Firmicutes to Bacteroidetes than overweight or normal weight groups (P = 0.01). Similarly at the genus level, overall bacterial distribution was highly associated with subjects’ body mass index (BMI). Treatment effects were observed between MUFA- and PUFA-rich diets, with the three MUFA diets elevating Parabacteroides, Prevotella, Turicibacter, and Enterobacteriaceae’s populations, while the two PUFA-rich diets favored the higher abundance of Isobaculum. High MUFA content feedings also resulted in an increase of Parabacteroides and a decrease of Isobaculum in obese, but not overweight subjects. Data suggest that BMI is a predominant factor in characterization of human gut microbiota profile, and that MUFA-rich and PUFA-rich diets impact the composition of gut microbiota at lower taxonomical levels mainly in obese subjects.

Reduction in liver fat by dietary MUFA in type 2 diabetes is helped by enhanced hepatic fat oxidation.

The aim of this work was to investigate hepatic lipid metabolic processes possibly involved in the reduction of liver fat content (LF) observed in patients with type 2 diabetes after an isoenergetic diet enriched in monounsaturated fatty acids (MUFAs). This is an ancillary analysis of a published study. In a parallel-group design, 30 men and eight women, aged 35-70years, with type 2 diabetes and whose blood glucose was controlled satisfactorily (HbA1c < 7.5% [58mmol/mol]) by diet or diet plus metformin, were randomised by MINIM software to follow either a high-carbohydrate/high-fibre/low-glycaemic index diet (CHO/fibre diet, n = 20) or a high-MUFA diet (MUFA diet, n = 18) for 8weeks. The assigned diets were known for the participants and blinded for people doing measurements. Before and after intervention, LF was measured by 1H-MRS (primary outcome) and indirect indices of de novo lipogenesis (DNL) (serum triacylglycerol palmitic:linoleic acid ratio), stearoyl-CoA desaturase activity (SCD-1) (serum triacylglycerol palmitoleic:palmitic acid ratio) and hepatic β-oxidation of fatty acids (β-hydroxybutyrate plasma concentrations) were measured. LF was reduced by 30% after the MUFA diet, as already reported. Postprandial β-hydroxybutyrate incremental AUC (iAUC) was significantly less suppressed after the MUFA diet (n = 16) (-2504 ± 4488μmol/l × 360min vs baseline -9021 ± 6489μmol/l × 360min) while it was unchanged after the CHO/fibre diet (n = 17) (-8168 ± 9827μmol/l × 360min vs baseline -7206 ± 10,005μmol/l × 360min, p = 0.962) (mean ± SD, p = 0.043). In the participants assigned to the MUFA diet, the change in postprandial β-hydroxybutyrate iAUC was inversely associated with the change in LF (r = -0.642, p = 0.010). DNL and SCD-1 indirect indices did not change significantly after either of the dietary interventions. Postprandial hepatic oxidation of fatty acids is a metabolic process possibly involved in the reduction of LF by a MUFA-rich diet in patients with type 2 diabetes. ClinicalTrials.gov NCT01025856 FUNDING : The study was funded by Ministero Istruzione Università e Ricerca and Italian Minister of Health.

Current Evidence Supporting the Link Between Dietary Fatty Acids and Cardiovascular Disease.

Lack of consensus exists pertaining to the scientific evidence regarding effects of various dietary fatty acids on cardiovascular disease (CVD) risk. The objective of this article is to review current evidence concerning cardiovascular health effects of the main dietary fatty acid types; namely, trans (TFA), saturated (SFA), polyunsaturated (PUFA; n-3 PUFA and n-6 PUFA), and monounsaturated fatty acids (MUFA). Accumulating evidence shows negative health impacts of TFA and SFA; both may increase CVD risk. Policies have been proposed to reduce TFA and SFA consumption to less than 1 and 7% of energy intake, respectively. Cardiovascular health might be promoted by replacing SFA and TFA with n-6 PUFA, n-3 PUFA, or MUFA; however, the optimal amount of PUFA or MUFA that can be used to replace SFA and TFA has not been defined yet. Evidence suggests of the potential importance of restricting n-6 PUFA up to 10% of energy and obtaining an n-6/n-3 ratio as close as possible to unity, along with a particular emphasis on consuming adequate amounts of essential fatty acids. The latest evidence shows cardioprotective effects of MUFA-rich diets, especially when MUFA are supplemented with essential fatty acids; namely, docosahexaenoic acid. MUFA has been newly suggested to be involved in regulating fat oxidation, energy metabolism, appetite sensations, weight maintenance, and cholesterol metabolism. These favorable effects might implicate MUFA as the preferable choice to substitute for other fatty acids, especially given the declaration of its safety for up to 20% of total energy.

Monounsaturated fatty acids-rich diets in hypercholesterolemic-growing rats

The effects of replacing dietary saturated fat by different monounsaturated fatty acid (ω-9MUFA) sources on serum lipids, body fat and bone in growing hypercholesterolemic rats were studied. Rats received one of the six different diets: AIN-93G (control, C); extra virgin olive oil (OO) + C; high-oleic sunflower oil (HOSO) + C or atherogenic diet (AT) for 8 weeks; the remaining two groups received AT for 3 weeks and then, the saturated fat was replaced by an oil mixture of soybean oil added with OO or HOSO for 5 weeks. Rats consuming MUFA-rich diets showed the highest body fat, hepatic index and epididymal, intestinal and perirenal fat, and triglycerides. T-chol and non-HDL-chol were increased in HOSO rats but decreased in OO rats. Bone mineral content and density were higher in both OO and HOSO groups than in AT rats. This study casts caution to the generalization of the benefits of MUFA for the treatment of hypercholesterolemia.

Development of a Food-Exchange Model to Replace Saturated Fat wth MUFAs and n–6 PUFAs in Adults at Moderate Cardiovascular Risk

The recommendation to reduce saturated fatty acid (SFA) consumption to ≤10% of total energy (%TE) is a key public health target aimed at lowering cardiovascular disease (CVD) risk. Replacement of SFA with unsaturated fats may provide greater benefit than replacement with carbohydrates, yet the optimal type of fat is unclear. The aim of the DIVAS (Dietary Intervention and Vascular Function) study was to develop a flexible food-exchange model to investigate the effects of substituting SFAs with monounsaturated fatty acids (MUFAs) or n–6 (ω-6) polyunsaturated fatty acids (PUFAs) on CVD risk factors. In this parallel study, UK adults aged 21–60 y with moderate CVD risk (50% greater than the population mean) were identified using a risk assessment tool (n = 195; 56% females). Three 16-wk isoenergetic diets of specific fatty acid (FA) composition (%TE SFA:%TE MUFA:%TE n–6 PUFA) were designed using spreads, oils, dairy products, and snacks as follows: 1) SFA-rich diet (17:11:4; n = 65); 2) MUFA-rich diet (9:19:4; n = 64); and 3) n–6 PUFA-rich diet (9:13:10; n = 66). Each diet provided 36%TE total fat. Dietary targets were broadly met for all intervention groups, reaching 17.6 ± 0.4%TE SFA, 18.5 ± 0.3%TE MUFA, and 10.4 ± 0.3%TE n–6 PUFA in the respective diets, with significant overall diet effects for the changes in SFAs, MUFAs, and n–6 PUFAs between groups (P < 0.001). There were no differences in the changes of total fat, protein, carbohydrate, and alcohol intake or anthropometric measures between groups. Plasma phospholipid FA composition showed changes from baseline in the proportions of total SFAs, MUFAs, and n–6 PUFAs for each diet group, with the changes in SFAs and MUFAs differing between the groups (P < 0.001). In conclusion, successful implementation of the food-exchange model broadly achieved the dietary target intakes for the exchange of SFAs with MUFAs or n–6 PUFAs with minimal disruption to the overall diet in a free-living population. This trial was registered at clinicaltrials.gov>as NCT01478958.

Monounsaturated fatty acids and risk of cardiovascular disease: synopsis of the evidence available from systematic reviews and meta-analyses.

No dietary recommendations for monounsaturated fatty acids (MUFA) are given by the National Institute of Medicine, the United States Department of Agriculture, European Food and Safety Authority and the American Diabetes Association. In contrast, the Academy of Nutrition and Dietetics, and the Canadian Dietetic Association both promote <25% MUFA of daily total energy consumption, while the American Heart Association sets a limit of 20% MUFA in their respective guidelines. The present review summarizes systematic reviews and meta-analyses of randomized controlled trials and cohort studies investigating the effects of MUFA on cardiovascular and diabetic risk factors, cardiovascular events and cardiovascular death. Electronic database Medline was searched for systematic reviews and meta-analyses using “monounsaturated fatty acids”, “monounsaturated fat”, and “dietary fat” as search terms with no restriction to calendar date or language. Reference lists and clinical guidelines were searched as well. Sixteen relevant papers were identified. Several studies indicated an increase of HDL-cholesterol and a corresponding decrease in triacylglycerols following a MUFA-rich diet. The effects on total and LDL-cholesterol appeared not consistent, but no detrimental effects on blood lipids were observed. Values for systolic and diastolic blood pressure were found to be reduced both during short- and long-term protocols using high amounts of MUFA as compared to low-MUFA diets. In type 2 diabetic subjects, MUFA exerted a hypoglycemic effect and reduced glycosylated hemoglobin in the long term. Data from meta-analyses exploring evidence from long-term prospective cohort studies provide ambiguous results with respect to the effects of MUFA on risk of coronary heart disease (CHD). One meta-analysis reported an increase in CHD events, however, most meta-analyses observed a lesser number of cases in participants subjected to a high-MUFA protocol. Although no detrimental side effects of MUFA-rich diets were reported in the literature, there still is no unanimous rationale for MUFA recommendations in a therapeutic regimen. Additional long-term intervention studies are required to characterized efficacy and effectiveness of recommending MUFA-rich diet among general and clinical populations.

Effect of substituting saturated with monounsaturated fatty acids on serum visfatin levels and insulin resistance in overweight women: A randomized cross-over clinical trial

Objective: This study aimed to determine the effects of a monounsaturated fatty acids (MUFA)-rich diet on serum visfatin, interleukin-6 and insulin levels among overweight women. Design: In this randomized cross-over clinical trial, 17 premenopausal overweight women were included. Participants were randomly assigned to consume either a hypocaloric, saturated fatty acids (SFA)-rich diet (16% SFA and 8% MUFA) or a hypocaloric, MUFA-rich diet (16% MUFA and 8% SFA) for 12 weeks crossing over after a 2-week washout period. Percentages of energy from other macronutrients were similar between the two diets. Biochemical and anthropometric assessments were done at the first and at the end of each period. Statistical analyses were done using paired t-test. In all statistical analysis, p < 0.05 was considered as significant. Results: The participant's mean body mass index was 27.6 kg/m2. Mean percentages of MUFA intake were 13% during MUFA-rich diet and 7% during SFA-rich diet. The corresponding values for SFA intake were 8.5% and 14%, respectively. We failed to find any significant differences between two intervention diets in terms of their effect on the serum levels of IL-6, visfatin and insulin. However, serum visfatin and IL-6 levels increased during the SFA-rich diet (0.4 ± 0.4 ng/ml and 0.19 ± 0.3 pg/ml, respectively) and decreased during the MUFA-rich diet ( − 0.7 ± 0.5 ng/ml and − 0.17 ± 0.3 pg/ml, respectively). In spite of a slight reduction in both periods, changes in serum insulin levels did not reach significant levels comparing the two periods. Conclusions: Our findings did not support any significant effect of a MUFA-rich intake on serum IL-6 and insulin levels as compared with a SFA-rich diet; however, it has the potential to favourably affect serum visfatin levels.