ABSTRACT
Background: Dietary fat composition can affect ectopic lipid accumulation and, thereby, insulin resistance. Diets that are high in saturated fatty acids (SFAs) or polyunsaturated fatty acids ...(PUFAs) have different metabolic responses.
Objective: We investigated whether the epigenome of human adipose tissue is affected differently by dietary fat composition and general overfeeding in a randomized trial.
Design: We studied the effects of 7 wk of excessive SFA (n = 17) or PUFA (n = 14) intake (+750 kcal/d) on the DNA methylation of ~450,000 sites in human subcutaneous adipose tissue. Both diets resulted in similar body weight increases. We also combined the data from the 2 groups to examine the overall effect of overfeeding on the DNA methylation in adipose tissue.
Results: The DNA methylation of 4875 Cytosine-phosphate-guanine (CpG) sites was affected differently between the 2 diets. Furthermore, both the SFA and PUFA diets increased the mean degree of DNA methylation in adipose tissue, particularly in promoter regions. However, although the mean methylation was changed in 1797 genes e.g., alpha-ketoglutarate dependent dioxygenase (FTO), interleukin 6 (IL6), insulin receptor (INSR), neuronal growth regulator 1 (NEGR1), and proopiomelanocortin (POMC) by PUFAs, only 125 genes e.g., adiponectin, C1Q and collagen domain containing (ADIPOQ) were changed by SFA overfeeding. In addition, the SFA diet significantly altered the expression of 28 transcripts e.g., acyl-CoA oxidase 1 (ACOX1) and FAT atypical cadherin 1 (FAT1), whereas the PUFA diet did not significantly affect gene expression. When the data from the 2 diet groups were combined, the mean methylation of 1444 genes, including fatty acid binding protein 1 (FABP1), fatty acid binding protein 2 (FABP2), melanocortin 2 receptor (MC2R), MC3R, PPARG coactivator 1 α (PPARGC1A), and tumor necrosis factor (TNF), was changed in adipose tissue by overfeeding. Moreover, the baseline DNA methylation of 12 CpG sites that was annotated to 9 genes e.g., mitogen-activated protein kinase 7 (MAPK7), melanin concentrating hormone receptor 1 (MCHR1), and splicing factor SWAP homolog (SFRS8) was associated with the degree of weight increase in response to extra energy intake.
Conclusions: SFA overfeeding and PUFA overfeeding induce distinct epigenetic changes in human adipose tissue. In addition, we present data that suggest that baseline DNA methylation can predict weight increase in response to overfeeding in humans. This trial was registered at clinicaltrials.gov as NCT01427140.
Cardiovascular disease (CVD) is the leading global cause of death, accounting for 17.3 million deaths per year. Preventive treatment that reduces CVD by even a small percentage can substantially ...reduce, nationally and globally, the number of people who develop CVD and the costs of caring for them. This American Heart Association presidential advisory on dietary fats and CVD reviews and discusses the scientific evidence, including the most recent studies, on the effects of dietary saturated fat intake and its replacement by other types of fats and carbohydrates on CVD. In summary, randomized controlled trials that lowered intake of dietary saturated fat and replaced it with polyunsaturated vegetable oil reduced CVD by ≈30%, similar to the reduction achieved by statin treatment. Prospective observational studies in many populations showed that lower intake of saturated fat coupled with higher intake of polyunsaturated and monounsaturated fat is associated with lower rates of CVD and of other major causes of death and all-cause mortality. In contrast, replacement of saturated fat with mostly refined carbohydrates and sugars is not associated with lower rates of CVD and did not reduce CVD in clinical trials. Replacement of saturated with unsaturated fats lowers low-density lipoprotein cholesterol, a cause of atherosclerosis, linking biological evidence with incidence of CVD in populations and in clinical trials. Taking into consideration the totality of the scientific evidence, satisfying rigorous criteria for causality, we conclude strongly that lowering intake of saturated fat and replacing it with unsaturated fats, especially polyunsaturated fats, will lower the incidence of CVD. This recommended shift from saturated to unsaturated fats should occur simultaneously in an overall healthful dietary pattern such as DASH (Dietary Approaches to Stop Hypertension) or the Mediterranean diet as emphasized by the 2013 American Heart Association/American College of Cardiology lifestyle guidelines and the 2015 to 2020 Dietary Guidelines for Americans.
Depression represents one of the major causes of disability worldwide, with an important socioeconomic cost. Although many risk factors have been considered in its pathogenesis, nutrition seems to ...play a determinant role in its prevention. With regard to individual macronutrients, dietary fats and especially n-3 polyunsaturated fatty acids (n-3 PUFA) are the most studied. However, previous data about other dietary fatty acids, such as n-6 PUFA, are conflicting, and little is known about saturated fatty acids (SFA), especially when considering carbon chain length. Thus, we investigated whether single types and subtypes of dietary fats are related to depressive symptoms in Italian individuals living in the Mediterranean area.
Dietary and socio-demographic data of 1572 individuals were analyzed. Food frequency questionnaires (FFQs) were used to determine the consumption of total dietary fat and each specific class of dietary fat, such as SFA, monounsaturated fatty acid (MUFA), and PUFA. The intake of fatty acids was also assessed according to the carbon-chain length of each single class. The Center for Epidemiologic Studies Depression Scale (CES-D) was used as a screening tool for depressive symptoms.
After adjustment for potential confounding factors, a significant inverse association between low/moderate levels of PUFA intake and depressive symptoms (Q2 vs. Q1, odds ratio (OR) = 0.60, 95% CI: 0.44, 0.84) was found. On the other hand, moderate saturated fat consumption was associated with depressive symptoms (Q3 vs. Q1, OR = 1.44, 95% CI: 1.02, 2.04). However, when considering carbon chain length, individuals with a lower to moderate intake of short-chain saturated fatty acids (SCSFA) and medium-chain saturated fatty acids (MCSFA) were less likely to have depressive symptoms (Q3 vs. Q1, OR = 0.48, 95% CI: 0.31, 0.75), while moderate intake of arachidic acid (C20:0) was directly associated with depressive symptoms (Q3 vs. Q1, OR = 1.87, 95% CI: 1.26, 2.77). Among single MUFAs, higher myristoleic acid (C14:1) intake was directly associated with depressive symptoms (Q4 vs. Q1, OR = 1.71, 95% CI: 1.12, 2.61), while moderate intake of erucic acid (C22:1) was associated with lower odds of having depressive symptoms (Q3 vs. Q1, OR = 0.54, 95% CI: 0.33, 0.86). When considering individual PUFAs, individuals with moderate and higher intakes of arachidonic acid (C20:4) were less likely to have depressive symptoms (OR = 0.64, 95% CI: 0.45, 0.91; OR = 0.59, 95% CI: 0.38, 0.91, respectively). Similarly, higher eicosapentaenoic acid (C20:5) intake was inversely associated with depressive symptoms (Q4 vs. Q1, OR = 0.35, 95% CI: 0.12, 0.98), while a significant association for docosahexaenoic acid (C22:6) was retrieved only for low intakes (Q2 vs. Q1, OR = 0.33, 95% CI: 0.12, 0.88).
Dietary fat intake may be associated with depressive symptoms, underlying the importance of distinguishing between different fat types. This study confirms the pivotal role of PUFAs and reopens the debate on the role of saturated fatty acids, suggesting plausible effects of moderate intakes of short-chain fatty acids.
Lipid oxidation is important to food manufacturers especially when they increase unsaturated lipids in their products to improve nutritional profiles. Unfortunately, the number of antioxidants ...available to food manufacturers to control oxidative rancidity is limited and the approval of new antioxidants is unlikely due to economic barriers in obtaining government approval for new food additives. Therefore, new antioxidant technologies are needed for food oils. This paper reviews the current knowledge of lipid oxidation in foods with emphasis on how physical properties of food systems impact oxidation chemistry. In particular, the role of association colloids in bulk oils on lipid oxidation chemistry is discussed in an attempt to understand mechanisms of oxidation. Increasing the understanding of how physical properties impact lipid oxidation could lead to the development of novel antioxidant technologies that not only protect the oil against oxidation and increase shelf-life but also allow food manufacturers to include more nutritionally beneficial fatty acids in their products.
Abstract This is a qualitative review of the evidence linking dietary fat composition to the risk of developing dementia. The review considers laboratory and animal studies that identify underlying ...mechanisms as well as prospective epidemiologic studies linking biochemical or dietary fatty acids to cognitive decline or incident dementia. Several lines of evidence provide support for the hypothesis that high saturated or trans fatty acids increase the risk of dementia and high polyunsaturated or monounsaturated fatty acids decrease risk. Dietary fat composition is an important factor in blood-brain barrier function and the blood cholesterol profile. Cholesterol and blood-brain barrier function are involved in the neuropathology of Alzheimer's disease, and the primary genetic risk factor for Alzheimer's disease, apolipoprotein E-ε4, is involved in cholesterol transport. The epidemiologic literature is seemingly inconsistent on this topic, but many studies are difficult to interpret because of analytical techniques that ignored negative confounding by other fatty acids, which likely resulted in null findings. The studies that appropriately adjust for confounding by other fats support the dietary fat composition hypothesis.
Based on decades of research, there is strong evidence that supports ongoing dietary recommendations to decrease intakes of SFAs and, more recently, to replace SFAs with unsaturated fat, including ...PUFAs and MUFAs. Epidemiologic research has shown that replacement of SFAs with unsaturated fat, but not refined carbohydrate and added sugars, is associated with a reduction in coronary heart disease events and death. There is much evidence from controlled clinical studies demonstrating that SFAs increase LDL cholesterol, a major causal factor in the development of cardiovascular disease. When each (nonprotein) dietary macronutrient isocalorically replaces SFA, the greatest LDL-cholesterol–lowering effect is seen with PUFA, followed by MUFA, and then total carbohydrate. New research on full-fat dairy products high in saturated fat, particularly fermented dairy foods, demonstrates some benefits for cardiometabolic diseases. However, compared with food sources of unsaturated fats, full-fat dairy products increase LDL cholesterol. Thus, current dietary recommendations to decrease SFA and replace it with unsaturated fat should continue to the basis for healthy food-based dietary patterns.
Background: Dietary fats, and especially saturated fatty acid (SFA), have been blamed for being the culprit in the dramatic increase in obesity and its associated diseases. However multiple ...systematic reviews and recent meta-analyses do not support the association between SFA and cardiovascular diseases. Thus, the objective of this study was to test whether specific types and subtypes of dietary fats are associated with metabolic outcomes in a cohort of Italian adults. Methods: Nutritional and demographic data of 1936 adults living in the south of Italy were examined. Food frequency questionnaires (FFQs) were administered to assess the intake of total dietary fat and each specific class of dietary fat, such as SFA, monounsaturated fatty acid (MUFA) and polyunsaturated fatty acid (PUFA). The intake of fatty acids was also examined according to the carbon-chain length of each individual class. Cases of hypertension, type-2 diabetes and dyslipidemias were collected from previous doctor-confirmed diagnosis records (or direct measurement of blood pressure). Results: After adjustment for potential confounding factors, individuals reporting higher intakes of total and saturated fats were associated with lower likelihood of having hypertension (odds ratio (OR) = 0.57, 95% CI: 0.35, 0.91 and OR = 0.55, 95% CI: 0.34, 0.89, respectively). Moreover, higher intake of short-chain saturated fatty acids (SCSFAs) and medium-chain saturated fatty acids (MCSFAs) was inversely associated with dyslipidemia and diabetes (OR = 0.43, 95% CI: 0.23, 0.82 and OR = 0.25, 95% CI: 0.09, 0.72, respectively). Among MUFAs, C18:1 was inversely associated with hypertension and diabetes (OR = 0.52, 95% CI: 0.30, 0.92 and OR = 0.21, 95% CI: 0.07, 0.67, respectively), while C14:1 intake was inversely associated only with hypertension (OR = 0.57, 95% CI: 0.37, 0.88). In contrast, C20:1 intake was associated with dyslipidemia (OR = 3.35, 95% CI: 1.33, 8.42). Regarding PUFA, C18:2 and 20:5 were inversely associated with hypertension (OR = 0.33, 95% CI: 0.18, 0.60 and OR = 0.30, 95% CI: 0.10, 0.89, respectively). Conclusions: The consumption of SFA does not seem to be harmful to cardio-metabolic health and, on the contrary, SCSFA may exert beneficial effects. Further studies are needed to clearly validate the results of the present study.
The carbohydrate-insulin model of obesity posits that high-carbohydrate diets lead to excess insulin secretion, thereby promoting fat accumulation and increasing energy intake. Thus, low-carbohydrate ...diets are predicted to reduce ad libitum energy intake as compared to low-fat, high-carbohydrate diets. To test this hypothesis, 20 adults aged 29.9 ± 1.4 (mean ± s.e.m.) years with body mass index of 27.8 ± 1.3 kg m
were admitted as inpatients to the National Institutes of Health Clinical Center and randomized to consume ad libitum either a minimally processed, plant-based, low-fat diet (10.3% fat, 75.2% carbohydrate) with high glycemic load (85 g 1,000 kcal
) or a minimally processed, animal-based, ketogenic, low-carbohydrate diet (75.8% fat, 10.0% carbohydrate) with low glycemic load (6 g 1,000 kcal
) for 2 weeks followed immediately by the alternate diet for 2 weeks. One participant withdrew due to hypoglycemia during the low-carbohydrate diet. The primary outcomes compared mean daily ad libitum energy intake between each 2-week diet period as well as between the final week of each diet. We found that the low-fat diet led to 689 ± 73 kcal d
less energy intake than the low-carbohydrate diet over 2 weeks (P < 0.0001) and 544 ± 68 kcal d
less over the final week (P < 0.0001). Therefore, the predictions of the carbohydrate-insulin model were inconsistent with our observations. This study was registered on ClinicalTrials.gov as NCT03878108 .
The carbohydrate-insulin model of obesity posits that habitual consumption of a high-carbohydrate diet sequesters fat within adipose tissue because of hyperinsulinemia and results in adaptive ...suppression of energy expenditure (EE). Therefore, isocaloric exchange of dietary carbohydrate for fat is predicted to result in increased EE, increased fat oxidation, and loss of body fat. In contrast, a more conventional view that "a calorie is a calorie" predicts that isocaloric variations in dietary carbohydrate and fat will have no physiologically important effects on EE or body fat.
We investigated whether an isocaloric low-carbohydrate ketogenic diet (KD) is associated with changes in EE, respiratory quotient (RQ), and body composition.
Seventeen overweight or obese men were admitted to metabolic wards, where they consumed a high-carbohydrate baseline diet (BD) for 4 wk followed by 4 wk of an isocaloric KD with clamped protein. Subjects spent 2 consecutive days each week residing in metabolic chambers to measure changes in EE (EEchamber), sleeping EE (SEE), and RQ. Body composition changes were measured by dual-energy X-ray absorptiometry. Average EE during the final 2 wk of the BD and KD periods was measured by doubly labeled water (EEDLW).
Subjects lost weight and body fat throughout the study corresponding to an overall negative energy balance of ∼300 kcal/d. Compared with BD, the KD coincided with increased EEchamber (57 ± 13 kcal/d, P = 0.0004) and SEE (89 ± 14 kcal/d, P < 0.0001) and decreased RQ (-0.111 ± 0.003, P < 0.0001). EEDLW increased by 151 ± 63 kcal/d (P = 0.03). Body fat loss slowed during the KD and coincided with increased protein utilization and loss of fat-free mass.
The isocaloric KD was not accompanied by increased body fat loss but was associated with relatively small increases in EE that were near the limits of detection with the use of state-of-the-art technology. This trial was registered at clinicaltrials.gov as NCT01967563.
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