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1.
Fatty Acids and Cardiovascular Risk. Evidence, Lack of Evidence, and Diligence.
Visioli, F, Poli, A
Nutrients. 2020;(12)
Abstract
One of the most controversial areas of nutrition research relates to fats, particularly essential fatty acids, in the context of cardiovascular disease risk. A critical feature of dietary fatty acids is that they incorporate into the plasma membrane, modifying fluidity and key physiological functions. Importantly, they can reshape the bioavailability of eicosanoids and other lipid mediators, which direct cellular responses to external stimuli, such as inflammation and chronic stress conditions. This paper provides an overview of the most recent evidence, as well as historical controversies, linking fat consumption with human health and disease. We underscore current pitfalls in the area of fatty acid research and critically frame fatty acid intake in the larger context of diet and behavior. We conclude that fundamental research on fatty acids and lipids is appropriate in certain areas, but the rigor and reproducibility are lacking in others. The pros and cons are highlighted throughout the review, seeking to guide future research on the important area of nutrition, fat intake, and cardiovascular disease risk.
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2.
The influence of dietary fatty acids on liver fat content and metabolism.
Hodson, L, Rosqvist, F, Parry, SA
The Proceedings of the Nutrition Society. 2020;(1):30-41
Abstract
Non-alcoholic fatty liver disease encompasses a spectrum of conditions from hepatic steatosis through to cirrhosis; obesity is a known risk factor. The liver plays a major role in regulating fatty acid metabolism and perturbations in intrahepatic processes have potential to impact on metabolic health. It remains unclear why intra-hepatocellular fat starts to accumulate, but it likely involves an imbalance between fatty acid delivery to the liver, fatty acid synthesis and oxidation within the liver and TAG export from the liver. As man spends the majority of the day in a postprandial rather than postabsorptive state, dietary fatty acid intake should be taken into consideration when investigating why intra-hepatic fat starts to accumulate. This review will discuss the impact of the quantity and quality of dietary fatty acids on liver fat accumulation and metabolism, along with some of the potential mechanisms involved. Studies investigating the role of dietary fat in liver fat accumulation, although surprisingly limited, have clearly demonstrated that it is total energy intake, rather than fat intake per se, that is a key mediator of liver fat content; hyperenergetic diets increase liver fat whilst hypoenergetic diets decrease liver fat content irrespective of total fat content. Moreover, there is now, albeit limited evidence emerging to suggest the composition of dietary fat may also play a role in liver fat accumulation, with diets enriched in saturated fat appearing to increase liver fat content to a greater extent when compared with diets enriched in unsaturated fats.
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3.
Lipids in the tumor microenvironment: From cancer progression to treatment.
Corn, KC, Windham, MA, Rafat, M
Progress in lipid research. 2020;:101055
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Abstract
Over the past decade, the study of metabolic abnormalities in cancer cells has risen dramatically. Cancer cells can thrive in challenging environments, be it the hypoxic and nutrient-deplete tumor microenvironment or a distant tissue following metastasis. The ways in which cancer cells utilize lipids are often influenced by the complex interactions within the tumor microenvironment and adjacent stroma. Adipocytes can be activated by cancer cells to lipolyze their triglyceride stores, delivering secreted fatty acids to cancer cells for uptake through numerous fatty acid transporters. Cancer-associated fibroblasts are also implicated in lipid secretion for cancer cell catabolism and lipid signaling leading to activation of mitogenic and migratory pathways. As these cancer-stromal interactions are exacerbated during tumor progression, fatty acids secreted into the microenvironment can impact infiltrating immune cell function and phenotype. Lipid metabolic abnormalities such as increased fatty acid oxidation and de novo lipid synthesis can provide survival advantages for the tumor to resist chemotherapeutic and radiation treatments and alleviate cellular stresses involved in the metastatic cascade. In this review, we highlight recent literature that demonstrates how lipids can shape each part of the cancer lifecycle and show that there is significant potential for therapeutic intervention surrounding lipid metabolic and signaling pathways.
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4.
Saturated Fats and Health: A Reassessment and Proposal for Food-Based Recommendations: JACC State-of-the-Art Review.
Astrup, A, Magkos, F, Bier, DM, Brenna, JT, de Oliveira Otto, MC, Hill, JO, King, JC, Mente, A, Ordovas, JM, Volek, JS, et al
Journal of the American College of Cardiology. 2020;(7):844-857
Abstract
The recommendation to limit dietary saturated fatty acid (SFA) intake has persisted despite mounting evidence to the contrary. Most recent meta-analyses of randomized trials and observational studies found no beneficial effects of reducing SFA intake on cardiovascular disease (CVD) and total mortality, and instead found protective effects against stroke. Although SFAs increase low-density lipoprotein (LDL) cholesterol, in most individuals, this is not due to increasing levels of small, dense LDL particles, but rather larger LDL particles, which are much less strongly related to CVD risk. It is also apparent that the health effects of foods cannot be predicted by their content in any nutrient group without considering the overall macronutrient distribution. Whole-fat dairy, unprocessed meat, and dark chocolate are SFA-rich foods with a complex matrix that are not associated with increased risk of CVD. The totality of available evidence does not support further limiting the intake of such foods.
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Maternal dietary fatty acids and their roles in human placental development.
Duttaroy, AK, Basak, S
Prostaglandins, leukotrienes, and essential fatty acids. 2020;:102080
Abstract
Fatty acids are essential for feto-placental growth and development. Maternal fatty acids and their metabolites are involved in every stage of pregnancy by supporting cell growth and development, cell signaling, and modulating other critical aspects of structural and functional processes. Early placentation process is critical for placental growth and function. Several fatty acids modulate angiogenesis as observed by increased tube formation and secretion of angiogenic growth factors in first-trimester human placental trophoblasts. Long-chain fatty acids stimulate angiogenesis in these cells via vascular endothelium growth factor (VEGF), angiopoietin-like protein 4 (ANGPTL4), fatty acid-binding proteins (FABPs), or eicosanoids. Inadequate placental angiogenesis and trophoblast invasion of the maternal decidua and uterine spiral arterioles leads to structural and functional deficiency of placenta, which contributes to preeclampsia, pre-term intrauterine growth restriction, and spontaneous abortion and also affects overall fetal growth and development. During the third trimester of pregnancy, placental preferential transport of maternal plasma long-chain polyunsaturated fatty acids is of critical importance for fetal growth and development. Fatty acids cross the placental microvillous and basal membranes by mainly via plasma membrane fatty acid transport system (FAT, FATP, p-FABPpm, & FFARs) and cytoplasmic FABPs. Besides, a member of the major facilitator superfamily-MFSD2a, present in the placenta is involved in the supply of DHA to the fetus. Maternal factors such as diet, obesity, endocrine, inflammation can modulate the expression and activity of the placental fatty acid transport activity and thereby impact feto-placental growth and development. In this review, we discuss the maternal dietary fatty acids, and placental transport and metabolism, and their roles in placental growth and development.
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6.
The Importance of Fatty Acids as Nutrients during Post-Exercise Recovery.
Lundsgaard, AM, Fritzen, AM, Kiens, B
Nutrients. 2020;(2)
Abstract
It is well recognized that whole-body fatty acid (FA) oxidation remains increased for several hours following aerobic endurance exercise, even despite carbohydrate intake. However, the mechanisms involved herein have hitherto not been subject to a thorough evaluation. In immediate and early recovery (0-4 h), plasma FA availability is high, which seems mainly to be a result of hormonal factors and increased adipose tissue blood flow. The increased circulating availability of adipose-derived FA, coupled with FA from lipoprotein lipase (LPL)-derived very-low density lipoprotein (VLDL)-triacylglycerol (TG) hydrolysis in skeletal muscle capillaries and hydrolysis of TG within the muscle together act as substrates for the increased mitochondrial FA oxidation post-exercise. Within the skeletal muscle cells, increased reliance on FA oxidation likely results from enhanced FA uptake into the mitochondria through the carnitine palmitoyltransferase (CPT) 1 reaction, and concomitant AMP-activated protein kinase (AMPK)-mediated pyruvate dehydrogenase (PDH) inhibition of glucose oxidation. Together this allows glucose taken up by the skeletal muscles to be directed towards the resynthesis of glycogen. Besides being oxidized, FAs also seem to be crucial signaling molecules for peroxisome proliferator-activated receptor (PPAR) signaling post-exercise, and thus for induction of the exercise-induced FA oxidative gene adaptation program in skeletal muscle following exercise. Collectively, a high FA turnover in recovery seems essential to regain whole-body substrate homeostasis.
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The Metformin Paradox.
Weijers, RNM, Bekedam, DJ
Current diabetes reviews. 2020;(2):143-147
Abstract
INTRODUCTION The Diabetes Prevention Program study results indicated that metformin therapy was not as beneficial as a lifestyle modification for delaying the development of type 2 diabetes in individuals at high risk of the disease. A key feature in the etiology of type 2 diabetes mellitus, which appears in the prediabetic phase, is a significant deficiency, compared to healthy controls, in highly flexible poly-cis-unsaturated fatty acyl chains in membrane phospholipids. This deficiency lowers membrane flexibility, which in turn, reduces the amount of all functional Class I glucose transporters, and thereby reduces glucose-mediated ATP production. This leads to an increase in essentially saturated free fatty acid (FFA) levels for fatty-acid-mediated ATP production, which will set up a vicious cycle of raising the levels of essentially saturated FFAs and lowering the level of transmembrane glucose transport. Metformin suppresses hepatic gluconeogenesis, which reduces the plasma glucose concentration. CONCLUSION We hypothesize that chronic metformin treatment leads to an additional increase in essentially saturated FFAs, which causes an additional rise in membrane stiffness and hypoxia. So we propose that all these metformin-mediated activities accelerated the onset of type 2 diabetes in the participants of the metformin group in the Diabetes Prevention Program study, compared to the participants of the lifestyle-intervention group in this study. We propose that the biochemical reactions, involved in the fatty-acid-mediated ATP production, play an important part in the increase of the observed essentially saturated FFA concentrations. These statements should also extend to the metformin therapy of individuals with type 2 diabetes.
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Diet Quality, Saturated Fat and Metabolic Syndrome.
Harrison, S, Couture, P, Lamarche, B
Nutrients. 2020;(11)
Abstract
Indices reflecting overall diet quality are used globally in research to predict the risk of various diseases and metabolic disorders such as metabolic syndrome (MetS). Such indices are built to measure adherence to current dietary guidelines or to best assess the diet-disease relationship. Although mostly food-based, dietary guidelines often include recommendations to limit saturated fatty acid (SFA) intake in order to prevent cardiovascular diseases. However, not all diet quality indices consider SFA in their definition of diet quality. Additionally, the relationship between SFA consumption and the development of MetS remains unclear. The purpose of this short review was to explore the association between MetS and various diet quality indices and dietary patterns, with a focus on how SFA contributes to these associations.
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9.
Clinical manifestations and management of fatty acid oxidation disorders.
Merritt, JL, MacLeod, E, Jurecka, A, Hainline, B
Reviews in endocrine & metabolic disorders. 2020;(4):479-493
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Abstract
Fatty acid oxidation disorders (FAOD) are a group of rare, autosomal recessive, metabolic disorders caused by variants of the genes for the enzymes and proteins involved in the transport and metabolism of fatty acids in the mitochondria. Those affected by FAOD are unable to convert fatty acids into tricarboxylic acid cycle intermediates such as acetyl-coenzyme A, resulting in decreased adenosine triphosphate and glucose for use as energy in a variety of high-energy-requiring organ systems. Signs and symptoms may manifest in infants but often also appear in adolescents or adults during times of increased metabolic demand, such as fasting, physiologic stress, and prolonged exercise. Patients with FAOD present with a highly heterogeneous clinical spectrum. The most common clinical presentations include hypoketotic hypoglycemia, liver dysfunction, cardiomyopathy, rhabdomyolysis, and skeletal myopathy, as well as peripheral neuropathy and retinopathy in some subtypes. Despite efforts to detect FAOD through newborn screening and manage patients early, symptom onset can be sudden and serious, even resulting in death. Therefore, it is critical to identify quickly and accurately the key signs and symptoms of patients with FAOD to manage metabolic decompensations and prevent serious comorbidities.
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10.
Low carbohydrate diet: are concerns with saturated fat, lipids, and cardiovascular disease risk justified?
Diamond, DM, O'Neill, BJ, Volek, JS
Current opinion in endocrinology, diabetes, and obesity. 2020;(5):291-300
Abstract
PURPOSE OF REVIEW There is an extensive literature on the efficacy of the low carbohydrate diet (LCD) for weight loss, and in the improvement of markers of the insulin-resistant phenotype, including a reduction in inflammation, atherogenic dyslipidemia, hypertension, and hyperglycemia. However, critics have expressed concerns that the LCD promotes unrestricted consumption of saturated fat, which may increase low-density lipoprotein (LDL-C) levels. In theory, the diet-induced increase in LDL-C increases the risk of cardiovascular disease (CVD). The present review provides an assessment of concerns with the LCD, which have focused almost entirely on LDL-C, a poor marker of CVD risk. We discuss how critics of the LCD have ignored the literature demonstrating that the LCD improves the most reliable CVD risk factors. RECENT FINDINGS Multiple longitudinal clinical trials in recent years have extended the duration of observations on the safety and effectiveness of the LCD to 2-3 years, and in one study on epileptics, for 10 years. SUMMARY The present review integrates a historical perspective on the LCD with a critical assessment of the persistent concerns that consumption of saturated fat, in the context of an LCD, will increase risk for CVD.