Dairy is a major food group with potential impact on cardiometabolic health. Self-reported dairy intake has limitations that can partly be avoided by using biomarkers. This review aims to summarize ...the evidence of odd-chain saturated fatty acids (OCFAs), that is, pentadecanoic acid (C15 : 0) and heptadecanoic acid (17 : 0), as biomarkers of dairy fat intake. In addition, the associations of OCFA biomarkers with cardiometabolic disease will be overviewed.
Adipose tissue 15 : 0 is the preferred biomarker but also circulating 15 : 0, and to a weaker extent 17 : 0, reflects both habitual and changes in dairy intake. Whereas results from studies assessing cardiovascular outcomes are inconsistent, OCFA biomarkers are overall associated with lower diabetes risk. Residual confounding should however be considered until interventional data and mechanisms are available. Although OCFA biomarkers mainly reflect dairy fat intake, recently proposed endogenous synthesis and metabolism do motivate further research.
Taking into account the study population diet and limitations of OCFA biomarkers, both adipose and circulating levels of 15 : 0, in particular, are useful for estimating total dairy fat intake. OCFA biomarkers are overall not linked to cardiovascular disease risk, but a possible beneficial role of dairy foods in diabetes prevention warrant further study.
Fatty acids and insulin sensitivity Risérus, Ulf
Current opinion in clinical nutrition and metabolic care,
2008-March, Letnik:
11, Številka:
2
Journal Article
Recenzirano
Given the pathophysiological importance of insulin resistance, the potential impact of dietary fatty acids is highly relevant. The effects of different types of dietary fatty acids on insulin ...sensitivity in humans are discussed, with focus on recent controlled studies.
Observational studies assessing fatty acid composition in serum or tissues suggest that insulin resistance is associated with relatively high intakes of saturated fat (e.g. palmitic acid) and low intakes of polyunsaturated fat (e.g. linoleic acid), findings that are supported by recent clinical data. Most controlled studies have hitherto examined the effect of monounsaturated fat on insulin sensitivity, several indicating that it has beneficial effects when substituted for saturated fat. More clinical data comparing n-6 polyunsaturated, monounsaturated and saturated fat are needed to identify the optimal dietary fat composition, especially in patients with insulin resistance/obesity and diabetes. The total fat content of the background diet should also be considered in future studies. Finally, we and others hypothesize that dietary fatty acids may partly mediate their effects on insulin action by regulating the activity of lipogenic enzymes and desaturases.
Substituting saturated fat with unsaturated fat seems to have beneficial effects on insulin sensitivity, although the clinical significance of modifying fat quality alone is still unclear.
The impact of most, but not all, cardiovascular risk factors decline by age. We investigated how the metabolic syndrome (MetS) was related to cardiovascular disease (CVD) during 40 years follow-up in ...the Uppsala Longitudinal Study of Adult Men (ULSAM, 2,123 men all aged 50 at baseline with reinvestigations at age 60, 70, 77 and 82). The strength of MetS as a risk factor of incident combined end-point of three outcomes (CVD) declined with ageing, as well as for myocardial infarction, ischemic stroke and heart failure when analysed separately. For CVD, the risk ratio declined from 2.77 (95% CI 1.90-4.05) at age 50 to 1.30 (95% CI 1.05-1.60) at age 82. In conclusion, the strength of MetS as a risk factor of incident CVD declined with age. Since MetS was significantly related to incident CVD also at old age, our findings suggest that the occurrence of MetS in the elderly should not be regarded as innocent. However, since our data were derived in an observational study, any impact of MetS in the elderly needs to be verified in a randomized clinical intervention trial.
Excess ectopic fat storage is linked to type 2 diabetes. The importance of dietary fat composition for ectopic fat storage in humans is unknown. We investigated liver fat accumulation and body ...composition during overfeeding saturated fatty acids (SFAs) or polyunsaturated fatty acids (PUFAs). LIPOGAIN was a double-blind, parallel-group, randomized trial. Thirty-nine young and normal-weight individuals were overfed muffins high in SFAs (palm oil) or n-6 PUFAs (sunflower oil) for 7 weeks. Liver fat, visceral adipose tissue (VAT), abdominal subcutaneous adipose tissue (SAT), total adipose tissue, pancreatic fat, and lean tissue were assessed by magnetic resonance imaging. Transcriptomics were performed in SAT. Both groups gained similar weight. SFAs, however, markedly increased liver fat compared with PUFAs and caused a twofold larger increase in VAT than PUFAs. Conversely, PUFAs caused a nearly threefold larger increase in lean tissue than SFAs. Increase in liver fat directly correlated with changes in plasma SFAs and inversely with PUFAs. Genes involved in regulating energy dissipation, insulin resistance, body composition, and fat-cell differentiation in SAT were differentially regulated between diets, and associated with increased PUFAs in SAT. In conclusion, overeating SFAs promotes hepatic and visceral fat storage, whereas excess energy from PUFAs may instead promote lean tissue in healthy humans.
Although type 2 diabetes is determined primarily by lifestyle and genes, dietary composition may affect both its development and complications. Dietary fat is of particular interest because fatty ...acids influence glucose metabolism by altering cell membrane function, enzyme activity, insulin signaling, and gene expression. This paper focuses on the prevention of type 2 diabetes and summarizes the epidemiologic literature on associations between types of dietary fat and diabetes risk. It also summarizes controlled feeding studies on the effects of dietary fats on metabolic mediators, such as insulin resistance. Taken together, the evidence suggests that replacing saturated fats and trans fatty acids with unsaturated (polyunsaturated and/or monounsaturated) fats has beneficial effects on insulin sensitivity and is likely to reduce risk of type 2 diabetes. Among polyunsaturated fats, linoleic acid from the n-6 series improves insulin sensitivity. On the other hand, long-chain n-3 fatty acids do not appear to improve insulin sensitivity or glucose metabolism. In dietary practice, foods rich in vegetable oils, including non-hydrogenated margarines, nuts, and seeds, should replace foods rich in saturated fats from meats and fat-rich dairy products. Consumption of partially hydrogenated fats should be minimized. Additional controlled, long-term studies are needed to improve our knowledge on the optimal proportion of different types of fats to prevent diabetes.
Purpose
Advice regarding the intake of dietary fats is particularly relevant to those with type 2 diabetes, given their increased risk of cardiovascular disease.
Methods
We have undertaken a ...systematic review of fat intakes and cardiovascular disease risk in adults with type 2 diabetes using an online search strategy to 24 April 2020, augmented with hand searching. Searches, extraction, and risk of bias assessments were undertaken by two researchers. The quality of evidence was assessed with GRADE protocols.
Results
We identified five eligible prospective studies of 22,591 participants followed for on average 9.8 years, and one trial of 14 participants with type 2 diabetes. Limited data were available; however, replacement analyses of saturated fat with polyunsaturated fat (RR for 2% energy replacement 0.87 95% CI: 0.77–0.99) or carbohydrate (RR for 5% energy replacement 0.82 95% CI: 0.67–1.00) was associated with reduced cardiovascular disease occurrence. Higher polyunsaturated: saturated fat intake was also associated with reduced cardiovascular disease occurrence (RR 0.75 95% CI: 0.57–0.98). The quality of evidence was low to very-low.
Conclusion
Although only limited data were available, replacement of saturated fats with other macronutrients, such as polyunsaturated fats, was associated with reduced cardiovascular disease occurrence. Supporting evidence from research in the general population increases confidence in these findings. Until more data are available to better comment on dietary fat intakes in cardiovascular disease risk of those with type 2 diabetes, it appears appropriate that saturated fats be replaced in the diet with other macronutrients, such as polyunsaturated fats.
Aims/hypothesis
The EFFECT-II study aimed to investigate the effects of dapagliflozin and omega-3 (
n
-3) carboxylic acids (OM-3CA), individually or combined, on liver fat content in individuals with ...type 2 diabetes and non-alcoholic fatty liver disease (NAFLD).
Methods
This randomised placebo-controlled double-blind parallel-group study was performed at five clinical research centres at university hospitals in Sweden. 84 participants with type 2 diabetes and NAFLD were randomly assigned 1:1:1:1 to four treatments by a centralised randomisation system, and all participants as well as investigators and staff involved in the study conduct and analyses were blinded to treatments. Each group received oral doses of one of the following: 10 mg dapagliflozin (
n
= 21), 4 g OM-3CA (
n
= 20), a combination of both (
n
= 22) or placebo (
n
= 21). The primary endpoint was liver fat content assessed by MRI (proton density fat fraction PDFF) and, in addition, total liver volume and markers of glucose and lipid metabolism as well as of hepatocyte injury and oxidative stress were assessed at baseline and after 12 weeks of treatment (completion of the trial).
Results
Participants had a mean age of 65.5 years (SD 5.9), BMI 31.2 kg/m
2
(3.5) and liver PDFF 18% (9.3). All active treatments significantly reduced liver PDFF from baseline, relative changes: OM-3CA, −15%; dapagliflozin, −13%; OM-3CA + dapagliflozin, −21%. Only the combination treatment reduced liver PDFF (
p
= 0.046) and total liver fat volume (relative change, −24%,
p =
0.037) in comparison with placebo. There was an interaction between the
PNPLA3
I148M polymorphism and change in liver PDFF in the active treatment groups (
p =
0.03). Dapagliflozin monotherapy, but not the combination with OM-3CA, reduced the levels of hepatocyte injury biomarkers, including alanine aminotransferase, aspartate aminotransferase, γ-glutamyl transferase (γ-GT), cytokeratin (CK) 18-M30 and CK 18-M65 and plasma fibroblast growth factor 21 (FGF21). Changes in γ-GT correlated with changes in liver PDFF (ρ
=
0.53,
p =
0.02). Dapagliflozin alone and in combination with OM-3CA improved glucose control and reduced body weight and abdominal fat volumes. Fatty acid oxidative stress biomarkers were not affected by treatments. There were no new or unexpected adverse events compared with previous studies with these treatments.
Conclusions/interpretation
Combined treatment with dapagliflozin and OM-3CA significantly reduced liver fat content. Dapagliflozin monotherapy reduced all measured hepatocyte injury biomarkers and FGF21, suggesting a disease-modifying effect in NAFLD.
Trial registration:
ClinicalTrials.gov
NCT02279407
Funding:
The study was funded by AstraZeneca.
This review aims to address the latest research on hepatic desaturases and metabolic disorders, with focus on stearoyl-CoA desaturase-1 (SCD-1) indices in observational studies.
In animal studies, ...SCD-1 inhibition protects against features of the metabolic syndrome and is associated with improved hepatic insulin resistance and decreased steatosis. In human observational studies, higher estimated hepatic SCD-1 and Δ6-desaturase activities predict the metabolic syndrome, insulin resistance and mortality whereas Δ5-desaturase index is often inversely related. However, because the desaturase activities in the liver and adipose tissue may not be regulated in parallel, it is important to define used lipid fractions when comparing studies. It is also important to take the background diets of the populations into account when comparing studies. Moreover, there may be a divergence in desaturase regulation depending on glycaemic control among individuals.
Increased SCD-1 indices reflecting liver desaturase activity have been associated with insulin resistance, fatty liver, the metabolic syndrome and mortality. However, it remains to be determined if high hepatic SCD-1 activity plays a direct role in the development of metabolic disorders or rather is a marker for an unfavourable diet or hepatic insulin resistance.
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.
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