Beef Fat Enriched with Polyunsaturated Fatty Acid Biohydrogenation Products Improves Insulin Sensitivity Without Altering Dyslipidemia in Insulin Resistant JCR:LA-cp Rats

The main dietary sources of trans fatty acids are partially hydrogenated vegetable oils (PHVO), and products derived from polyunsaturated fatty acid biohydrogenation (PUFA‐BHP) in ruminants. Trans fatty acid intake has historically been associated with negative effects on health, generating an anti‐trans fat campaign to reduce their consumption. The profiles and effects on health of PHVO and PUFA‐BHP can, however, be quite different. Dairy products naturally enriched with vaccenic and rumenic acids have many purported health benefits, but the putative benefits of beef fat naturally enriched with PUFA‐BHP have not been investigated. The objective of the present experiment was to determine the effects of beef peri‐renal fat (PRF) with differing enrichments of PUFA‐BHP on lipid and insulin metabolism in a rodent model of dyslipidemia and insulin resistance (JCR:LA‐cp rat). The results showed that 6 weeks of diet supplementation with beef PRF naturally enriched due to flaxseed (FS‐PRF) or sunflower‐seed (SS‐PRF) feeding to cattle significantly improved plasma fasting insulin levels and insulin sensitivity, postprandial insulin levels (only in the FS‐PRF) without altering dyslipidemia. Moreover, FS‐PRF but not SS‐PRF attenuated adipose tissue accumulation. Therefore, enhancing levels of PUFA‐BHP in beef PRF with FS feeding may be a useful approach to maximize the health‐conferring value of beef‐derived fats.     

Effects of Lipid Structure Changed by Interesterification on Melting Property and Lipemia

Interesterification or the randomization reaction changes fatty acid positional distribution and solid fat content of fats, which may consequently affect fat absorption and metabolism. It is well established that saturated fatty acids in the sn‐2 position of triacylglycerols (TAG) have better digestibility and lower postprandial chylomicron clearance compared to those in the sn‐1,3 positions in animal experiments. TAG structure is also shown to affect fasting lipid level and atherosclerosis in animals, but fat interesterification it has been shown to not affect fasting lipid level in human adults. However, its effect on postprandial responses is controversial. In this review, the complex results of studies of interesterification and lipemia were briefly discussed. More importantly, the confounding of two factors that are both changed by interesterification, TAG structure and solid fat content as the main limitation on understanding how interesterification affects lipemia is emphasized. Separation of the two factors is possible using paired fats as demonstrated. This paper also discusses some intriguing effects of fats having saturated fatty acids in the sn‐2 position and the need for future research.     

Postprandial Lipid Responses do not Differ Following Consumption of Butter or Vegetable Oil when Consumed with Omega-3 Polyunsaturated Fatty Acids

Dietary saturated fat (SFA) intake has been associated with elevated blood lipid levels and increased risk for the development of chronic diseases. However, some animal studies have demonstrated that dietary SFA may not raise blood lipid levels when the diet is sufficient in omega‐3 polyunsaturated fatty acids (n‐3PUFA). Therefore, in a randomised cross‐over design, we investigated the postprandial effects of feeding meals rich in either SFA (butter) or vegetable oil rich in omega‐6 polyunsaturated fatty acids (n‐6PUFA), in conjunction with n‐3PUFA, on blood lipid profiles [total cholesterol, low density lipoprotein cholesterol (LDL‐C), high density lipoprotein cholesterol (HDL‐C) and triacylglycerol (TAG)] and n‐3PUFA incorporation into plasma lipids over a 6‐h period. The incremental area under the curve for plasma cholesterol, LDL‐C, HDL‐C, TAG and n‐3PUFA levels over 6 h was similar in the n‐6PUFA compared to SFA group. The postprandial lipemic response to saturated fat is comparable to that of n‐6PUFA when consumed with n‐3PUFA; however, sex‐differences in response to dietary fat type are worthy of further attention.     

Postprandial Lipemia Detects the Effect of Soy Protein on Cardiovascular Disease Risk Compared with the Fasting Lipid Profile

Studies examining the effect of soy protein on cardiovascular disease (CVD) risk factors have not taken advantage of the postprandial state as an adjunct to the fasting lipid profile. The American Heart Association has acknowledged the efficacy of soy protein in reducing CVD risk factors to be limited. We hypothesized that the postprandial state would be more sensitive to any favorable changes associated with consuming soy protein compared with the fasting lipid profile. Furthermore, the presence of isoflavones in soy would enhance this effect. Thirty sedentary males aged 18–30 years were randomly assigned to milk protein (Milk), isoflavone-poor soy (Soy−), or isoflavone-rich soy (Soy+). Usual diets were supplemented with 25 g/day of protein for 28 days. Serum samples were collected before and after supplementation in a fasted state and postprandially at 30, 60, 120, 240, and 360 min after a high-fat, 1,000 kcal shake. Triacylglycerol (TAG), total cholesterol, non-esterified fatty acids, apolipoproteins B-100 and A-I and glucose concentrations were quantified. Fasting concentrations were not different after any protein supplementation. Postprandial TAG and TAG AUC increased after Soy-consumption supporting the postprandial state as a more sensitive indicator of soy ingestion effects on CVD risk factors compared with the fasting lipid profile. Furthermore, the absence of isoflavones in soy protein may have deleterious consequences on purported cardio-protective effects.     

Dietary Monounsaturated Fatty Acids Are Protective Against Metabolic Syndrome and Cardiovascular Disease Risk Factors

Over 50 years of research has sought to define the role dietary fat plays in cardiovascular disease (CVD) risk. Although optimal dietary fat quantity has been keenly pursued over past decades, attention has recently centered on the value of dietary fat quality. The purpose of the present review is to provide a critical assessment of the current body of evidence surrounding efficacy of dietary monounsaturated fatty acids (MUFA) for reduction of traditional risk factors defining metabolic syndrome (MetS) and CVD. Due to existing and emerging research on health attributes of MUFA rich diets, and to the low prevalence of chronic disease in populations consuming MUFA rich Mediterranean diets, national dietary guidelines are increasingly recommending dietary MUFA, primarily at the expense of saturated fatty acids (SFA). Consumption of dietary MUFA promotes healthy blood lipid profiles, mediates blood pressure, improves insulin sensitivity and regulates glucose levels. Moreover, provocative newer data suggest a role for preferential oxidation and metabolism of dietary MUFA, influencing body composition and ameliorating the risk of obesity. Mounting epidemiological and human clinical trial data continue to demonstrate the cardioprotective activity of the MUFA content of dietary fat. As the debate on the optimal fatty acid composition of the diet continues, the benefit of increasing MUFA intakes, particularly as a substitute for dietary SFA, deserves considerable attention.     

Role of n-3 Fatty Acids on Bile Acid Metabolism and Transport in Dyslipidemia: A Review

Dietary n-3 fatty acids, especially of marine origin, eicosapentaenoic acid (20:5n-3) and docosahexaenoic acid (22:6n-3), have always been lauded for their profound effects on regulating the risk factors for major metabolic disorders. Yet, their consumption rate is poor compared to n-6 fatty acids [linoleic acid (18:2n-6)], which are predominantly consumed. Hence, the skewed n-6 to n-3 fatty acid ratio may have a bearing on the risk factors of various diseases, including dyslipidemia. Dyslipidemia and other lifestyle diseases associated with it, such as diabetes, obesity, hypertension, are a growing concern in both developed and developing countries. A common strategy for addressing dyslipidemia involves bile acid (BA) sequestration, to interrupt the enterohepatic circulation of BA, resulting in the modulation of lipid absorption in the intestine, thereby normalizing the levels of circulating lipids. The BA homeostasis is under the tight control of hepatic and enteric BA transporters. Many investigations have reported the effects of dietary constituents, including certain fatty acids on the reabsorption and transport of BA. However, a critical review of the effects of n-3 fatty acids on BA metabolism and transport is not available. The present review attempts to explore certain unmapped facets of the n-3 fatty acids on BA metabolism and transport in dyslipidemia, and their interplay with biological processes involving lipid rafts and gut microbiome.     

Ginsenoside Rg3 Reduces Lipid Accumulation with AMP-Activated Protein Kinase (AMPK) Activation in HepG2 Cells

Cardiovascular disease (CVD) is one of the main causes of mortality worldwide, and dyslipidemia is a major risk factor for CVD. Ginseng has been widely used in the clinic to treat CVD. Ginsenoside Rg3, one of the major active components of ginseng, has been reported to exhibit antiobesity, antidiabetic, and cardioprotective effects. However, the effect of ginsenoside Rg3 on hepatic lipid metabolism remains unclear. Therefore, we investigated whether ginsenoside Rg3 would regulate hepatic lipid metabolism with AMP-activated protein kinase (AMPK) activation in HepG2 cells. Ginsenoside Rg3 significantly reduced hepatic cholesterol and triglyceride levels. Furthermore, ginsenoside Rg3 inhibited expression of sterol regulatory element binding protein-2 (SREBP-2) and 3-hydroxy-3-methyl glutaryl coenzyme A reductase (HMGCR). Ginsenoside Rg3 increased activity of AMPK, a major regulator of energy metabolism. These results suggest that ginsenoside Rg3 reduces hepatic lipid accumulation with inhibition of SREBP-2 and HMGCR expression and stimulation of AMPK activity in HepG2 cells. Therefore, ginsenoside Rg3 may be beneficial as a food ingredient to lower the risk of CVD by regulating dyslipidemia.     

Effect of a low-fat diet enriched with oleic acid on postprandial lipemia in patients with type 2 diabetes mellitus

The aim of the present study was to compare the effects of a low-fat diet enriched with oleic acid to those of a low-fat diet enriched with linoleic acid on fasting lipids, postprandial lipemia, and oxidative susceptibility of low-density lipoprotein (LDL) in patients with type 2 diabetes mellitus (DM). In a 3-wk randomized crossover study, eight patients with type 2 DM were given an experimental low-fat diet enriched with either oleic acid or linoleic acid. The oleic-acid-enriched diet contained 5, 15, and 5% energy from saturated, monounsaturated, and polyunsaturated fatty acids, and the linoleic-acid-enriched diet contained 5, 5, and 15% energy from saturated, monounsaturated, and polyunsaturated fatty acids, respectively. In addition to evaluating the fasting lipids and oxidative susceptibility of LDL, we evaluated postprandial lipemia using an oral fat load at the end of each 3-wk dietary phase. There were no significant differences in fasting lipid profile or lag time of LDL oxidation between the two experimental dietary phases. The average and maximal increments of remnant-like particle (RLP) cholesterol levels during oral fat load were significantly higher after the oleic-acid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. The area under the curve of RLP cholesterol was also significantly larger after the oleicacid-enriched dietary phase than after the linoleic-acid-enriched dietary phase. These results suggest that the oleic-acidenriched diet was associated with increased formation of postprandial chylomicron remnants compared with the linoleicacid-enriched diet.     

Postprandial triglyceride-rich lipoprotein metabolism and insulin sensitivity in nonalcoholic steatohepatitis patients

Nonalcoholic steatohepatitis (NASH) is a syndrome frequently associated with obesity, diabetes mellitus, and dyslipidemia. Increased fasting insulinemia and blood glucose levels may trigger a reduced catabolism of lipoproteins rich in triglycerides by lipoprotein lipase (LPL) and an increase in their fasting and postprandial levels. An association between postprandial lipemia and coronary heart disease has been observed, and many studies now support this concept. The most important result of our study is the increase in triglyceride-rich lipoproteins response after a fat load in NASH patients, the increase of incremental area under the postprandial curve, and the duration of the hypertriglyceridemic peaks. The persisting postprandial plasma triglyceride elevation in NASH patients was mostly due to the elevated plasma level of large triglyceride-rich particles. These data are coupled with lower plasma HDL2-cholesterol levels. As for lipoprotein analyses, the number of apolipoprotein B100 (ApoB100) particles is not significantly different between the two groups, and the higher content of triglycerides in NASH very low density lipoproteins (VLDL) increases the triglyceride-to-ApoB ratio and the particle size. A decreased enzymatic activity of LPL or a defective assembly and secretion of VLDL from hepatocytes due to a moderate reduction in microsomal triglyceride transfer protein could be involved in the overloading of VLDL. Moreover, the undetectable levels of ApoB48 in triglyceride-rich lipoproteins fraction A could be related to the synthesis of smaller and denser chylomicrons. NASH patients not only are insulin resistant but also tend to present alterations in fatty meal delivery, suggesting that an increase in fasting plasma insulin and glucose, with insulin resistance, joins with depressed metabolism of triglyceride-rich lipoproteins. An increase in postprandial triglyceride levels with production of large VLDL suggests an atherogenic behavior of lipid metabolism, in accordance with the high prevalence of the metabolic syndrome in NASH patients. This paper suggests that a fat load may be useful in early detection of atherogenic risk in the presence of otherwise normal fasting plasma lipids.     

Dietary Fatty Acid Metabolism is Affected More by Lipid Level than Source in Senegalese Sole Juveniles: Interactions for Optimal Dietary Formulation

This study analyses the effects of dietary lipid level and source on lipid absorption and metabolism in Senegalese sole (Solea senegalensis). Juvenile fish were fed 4 experimental diets containing either 100 % fish oil (FO) or 25 % FO and 75 % vegetable oil (VO; rapeseed, linseed and soybean oils) at two lipid levels (~8 or ~18 %). Effects were assessed on fish performance, body proximate composition and lipid accumulation, activity of hepatic lipogenic and fatty acid oxidative enzymes and, finally, on the expression of genes related to lipid metabolism in liver and intestine, and to intestinal absorption, both pre‐ and postprandially. Increased dietary lipid level had no major effects on growth and feeding performance (FCR), although fish fed FO had marginally better growth. Nevertheless, diets induced significant changes in lipid accumulation and metabolism. Hepatic lipid deposits were higher in fish fed VO, associated to increased hepatic ATP citrate lyase activity and up‐regulated carnitine palmitoyltransferase 1 (cpt1) mRNA levels post‐prandially. However, lipid level had a larger effect on gene expression of metabolic (lipogenesis and β‐oxidation) genes than lipid source, mostly at fasting. High dietary lipid level down‐regulated fatty acid synthase expression in liver and intestine, and increased cpt1 mRNA in liver. Large lipid accumulations were observed in the enterocytes of fish fed high lipid diets. This was possibly a result of a poor capacity to adapt to high dietary lipid level, as most genes involved in intestinal absorption were not regulated in response to the diet.     

9‐Oxo‐10(E),12(Z),15(Z)‐Octadecatrienoic Acid Activates Peroxisome Proliferator‐Activated Receptor α in Hepatocytes

The peroxisome proliferator‐activated receptor (PPAR)α is mainly expressed in the liver and plays an important role in the regulation of lipid metabolism. It has been reported that PPARα activation enhances fatty acid oxidation and reduces fat storage. Therefore, PPARα agonists are used to treat dyslipidemia. In the present study, we found that 9‐oxo‐10(E),12(Z),15(Z)‐octadecatrienoic acid (9‐oxo‐OTA), which is a α‐linolenic acid (ALA) derivative, is present in tomato (Solanum lycopersicum) extract. We showed that 9‐oxo‐OTA activated PPARα and induced the mRNA expression of PPARα target genes in murine primary hepatocytes. These effects promoted fatty acid uptake and the secretion of β‐hydroxybutyrate, which is one of the endogenous ketone bodies. We also demonstrated that these effects of 9‐oxo‐OTA were not observed in PPARα‐knockout (KO) primary hepatocytes. To our knowledge, this is the first study to report that 9‐oxo‐OTA promotes fatty acid metabolism via PPARα activation and discuss its potential as a valuable food‐derived compound for use in the management of dyslipidemia.     

Unravelling the complexity of health effects of trans fatty acids: Insight from the TRANSFACT study

The TRANSFACT study, a worldwide research initiative, revealed that the effects of trans fatty acids (TFA) found in ‘natural’ ruminant fat (R‐TFA) and industrially produced (IP‐TFA) sources on cardiovascular disease risk (CVD) factors are different. Moreover, it was observed for both dietary sources of TFA that women and men react differently to TFA consumption, the women being more sensitive than men. The TRANSFACT study demonstrates that the consumption of R‐TFA at the current level consumption does not impact significantly on CVD risk factors. Moreover, the TRANSFACT study confirmed that the complexity related to the consumption of TFA was oversimplified as recently suggested in an epidemiological study.     

Influence of stearic acid on hemostatic risk factors in humans

Stearic acid has been claimed to be prothrombotic. Elevated plasma factor VII coagulant activity (FVIIc) may raise the risk of coronary thrombosis in the event of plaque rupture. Fibrinogen, an acute-phase protein, is necessary for normal blood clotting; however, elevated levels of fibrinogen increase the risk of coronary heart disease (CHD). Here I report the results of three controlled, human dietary intervention studies, which used a randomized crossover design to investigate the hemostatic effects of stearic acid-rich test diets in healthy young men. A diet high in stearic acid (shea butter) resulted in a 13% lower fasting plasma FVIIc than a high palmitic acid diet, and was 18% lower than a diet high in myristic and lauric acids (P=0.001) after 3 wk of intervention. The stearic acid-rich test fat increased plasma fibrinogen concentrations slightly compared with the myristic-lauric acid diet (P<0.01). When investigating the acute effects of fatty meals, those high in stearic acid (synthesized test fat) resulted in a smaller postprandial increase in FVII than those high in trans and oleic FA, indicating a smaller increase in activated FVII after ingesting stearic acid compared with fats high in monounsaturated FA, probably caused by lower postprandial lipemia. Thus, the present investigations did not find dietary stearic acid to be more thrombogenic, in either fasting effects compared with other longchain FA, or in acute effects compared with dietary unsaturated FA, including trans monounsaturated FA. The slightly increased effect on fasting plasma fibrinogen may be biologically insignificant, but it should be investigated further.     

Diacylglycerol oil for the metabolic syndrome

Excess adiposity has been shown to play a crucial role in the development of the metabolic syndrome. The elevated fasting and postprandial triglyceride-rich lipoprotein levels is the central lipid abnormality observed in the metabolic syndrome. Recent studies have indicated that diacylglycerol (DAG) is effective for fasting and postprandial hyperlipidemia and preventing excess adiposity by increasing postprandial energy expenditure. We will here discuss the mechanisms of DAG-mediated improvements in hyperlipidemia and in postprandial energy expenditure, and effects of DAG oil on lipid/glucose metabolism and on body fat. Further, the therapeutic application of DAG for the metabolic syndrome will be considered.     

How do polyunsaturated fatty acids lower plasma cholesterol levels?

For 30 years it has been known that linoleic acid can lower elevated cholesterol levels. Large increases in linoleic acid have been widely recommended as a way of reducing the risk of cardiovascular disease. Such recommendations have resulted in major dietary shifts in some countries, including the USA. Yet the precise characteristics of the linoleic acid molecule which confer on it cholesterol-lowering properties are unknown. gamma-Linolenic acid, the first essential fatty acid metabolite of linoleic acid, has been found to have cholesterol-lowering actions ca. 170 times greater than the parent molecule, suggesting that linoleic acid must be converted to gamma-linolenic acid to exert its desirable effects on cholesterol metabolism. Aging, sex, diabetes mellitus, alcohol, catecholamines and trans fatty acids and saturated fats can all modulate the delta-6-desaturase enzyme which converts linoleic acid to gamma-linolenic acid. This provides a possible unifying explanation for the actions of these known risk factors for cardiovascular disease.     

Chemical Genetic Approaches for the Investigation of Neutral Lipid Metabolism

The coordinated processes of lipid synthesis, degradation, and transport are mediated by enzymes, cofactors, and transport proteins. Accordingly, lipid‐metabolizing enzymes represent logical targets for the treatment of dyslipidemia, a major risk factor for type 2 diabetes, atherosclerosis, and other disorders. Small‐molecule tool compounds, modulating the functions of such proteins, can substantially facilitate the characterization of target proteins. Such molecules complement genetic studies, and allow time‐ and dose‐dependent control of protein activity in biological systems. This can improve our understanding of physiological processes, give insights into the druggability of target proteins, and might finally result in the development of therapeutic compounds. In this review we summarize the current state of available inhibitors targeting key proteins in neutral lipid metabolism, with a focus on metabolic lipases, acyltransferases, and fatty‐acid‐binding proteins.     

Intake of ruminant versus industrial trans fatty acids and risk of coronary heart disease – what is the evidence?

Several studies have reported a positive association between intake of trans fatty acids and risk of heart disease. It has been suggested that trans fatty acids from ruminant sources are less detrimental than trans fatty acids from industrial sources. Legislation or advice on limiting trans fatty acids has, in some instances, been restricted to trans fatty acids from industrial sources. However, comparisons of ruminant and industrial trans fatty acids have been based on few studies using relative intake data (e.g. quintiles of intakes). Therefore, we have reviewed data describing the associations between absolute intake (g eaten per day) of ruminant and industrial trans fatty acids and risk of coronary heart disease, and examined the associations graphically. Where direct comparison is possible, there are no differences in risk of coronary heart disease between total, ruminant and industrial trans fatty acids for intakes up to 2.5 g/d. At higher intakes (more than 3 g/d) total and industrial trans fatty acids are associated with an increased risk of coronary heart disease but there is insufficient data available on ruminant trans fatty acids at this level of intake. The scarce data do not support discrimination between ruminant and industrial trans fatty acids in dietary recommendations or legislation.     

Bioactivity and emerging role of short and medium chain fatty acids

Cardiovascular disease (CVD) and insulin resistance are directly linked to overweight and obesity. Thus, any dietary strategy capable of causing weight reduction will lower CVD and diabetes risk. Oils rich in medium‐chain saturated fatty acids (MCFA) are among several dietary components that may have potential in the treatment of obesity. MCFA are less energy dense and highly ketogenic compared to long‐chain saturated and unsaturated fatty acids (LCFA). MCFA also differ from LCFA in their digestive and metabolic pathways, since they are easily oxidized and utilized as energy, with little tendency to deposit as body fat. The dietary intake of short (SCFA) and medium‐chain saturated fatty acids from natural food sources is approximately 2.4 g/day and accounts for about 9% of the total saturated fatty acid (SFA) intake. Although early clinical studies with high levels of MCFA resulted in increased levels of plasma triacylglycerols (TAG) and low‐density lipoprotein cholesterol (LDL‐C), and reduced levels of high‐density lipoprotein cholesterol (HDL‐C) compared to diets enriched in unsaturated LCFA, these adverse effects have not been observed in more recent studies with smaller more realistic amounts of MCFA. The lower caloric value of SCFA and MCFA and their unique metabolic features form the basis for their clinical use in enteral and parenteral nutrition and for novel reduced calorie lipids for use in conventional food products.