**2.1. Effects of MUFA and PUFA supplements on dyslipidemia associated to childhood obesity**

Supplementation with MUFA is supported by authoritative bodies. When MUFA replaces saturated fatty acids it reduces total cholesterol, and when MUFA replaces carbohydrates it

The atherogenic lipid profile is more severe in obese children, especially in boys, who are insulinoresistent. The severity of obesity estimated by the value of body mass index (BMI) is of a lesser importance in comparison with insulin resistance on the atherogenic lipid

The atherogenic index can be calculated in many ways, but the most used procedures are: as the ratio between total cholesterol to HDL cholesterol or as a ratio apoB/apoA1. By assessing atherogenic indexes, it has been demonstrated that overweight and obese children have twice higher risk of atherosclerosis [23] and that advancing puberty and advancing age are athero‐

The relation between plasma lipids and prediabetes in obese prepubertal children is proved by the association of saturated fatty acids in triglycerides with the HOMA-IR (homeostatic

In children, the process of atherosclerosis starts at an early age and is linked to visceral obesity [26]. The common carotid artery intima-media thickness (C-IMT) measured by ultrasound imaging is a marker of preclinical atherosclerosis. C-IMT relates to the severity and extent of

True primary prevention of atherosclerosis, as contrasted with primary prevention of clinically

Results from the Young Finns Study have shown that conventional childhood risk factors, such as dyslipidemia, obesity, elevated blood pressure, and smoking, are predictive of subclinical atherosclerosis in young adults [28]. The same authors of the study underline the good news that the adverse cardiometabolic effects of childhood overweight/obesity are reversed among

The relation cause-effect between dyslipidemia and insulin resistance is not well established but they are interdependent. Most of the researchers consider that insulin resistance precedes

Insulin resistance increases free fatty acid flux to the liver by decreased inhibition of lipolysis

Supplements with docosahexaenoic acid (DHA) reduce plasma concentrations of free fatty acids of LDL-c and the ratio triacylglycerols/HDL-c, improving insulin resistance [31].

Eicosapentaenoic acid (EPA) increases the anti-inflammatory monocyte cytokine IL-10 expression and reduces arterial stiffness, which may contribute to the antiatherogenic effect

the development of the metabolic syndrome feature, including dyslipidemia [29].

coronary artery disease and predicts the likelihood of cardiovascular events in adults.

manifest atherosclerotic disease, must begin in childhood or adolescence [27].

decreases triglycerides and increases HDL [21].

genic risk factors for obese boys [24].

those who become nonobese adults.

and also by increased de novo lipogenesis [30].

of EPA in obese dyslipidemic patients [32].

model assessment of insulin resistance) [25].

profile [22].

62 Lipoproteins - From Bench to Bedside

The MUFA from n-7 and n-9 classes can be synthesized in our body from acetyl-coA, but the essential PUFA from n-3 and n-6 classes are required in the diet. A balance between n-6 and n-3 PUFA must be maintained in the diet. There is no consensus about the value of this ratio, but the most used value is around 5. Linoleic acid (C18 delta 9,12) represents the parental fatty acid for class n-6 and linolenic acids (C18 delta 9,12,15) for class n-3, respectively. Naturally, the structure of unsaturated fatty acids is cis fatty acids. PUFA are incorporated in the structure of membrane phosphatides involved in cell fluidity, permeability, and signal transduction. n-3 PUFA are important in the brain development in the fetus and also in early postnatal life [19].

Differences in the composition of dietary fat may also contribute to adipose tissue development by altering rates of adipocyte differentiation and proliferation. Relatively low intake of n-3 PUFA and excessive dietary linoleate may contribute to excessive adipose tissue [33].

Postmortem examination of fetuses delivered from hypercholesterolemic mothers demon‐ strated that passivity in utero exposure to a hyperlipidemic environment may have program‐ med these children for accelerated atherosclerosis [34].

It was demonstrated that an enhanced maternal-fetal n-3 PUFA status was associated with lower childhood adiposity [35]. But, in another study, supplementation with n-3 fatty acids during pregnancy and lactation didn't influence significantly the fat mass in the offspring during the first year of life [36]. Good news is that fish oil supplementation during lactation affects blood pressure and body composition of children [37] and that nutritional interventions may improve plasma long-chain PUFA profile and metabolic outcomes of normolipidaemic obese children [38].

According to the European directive, the infant formula should be enriched with long-chain PUFA because this supplementation is associated with lower blood pressure during later childhood. In clinical studies done in adults, fish oil supplementation gave varying results on blood pressure values but most of them showed a lowering in the blood values [19].

A decrease in serum n-3 PUFA, especially DHA, and an increase in saturated FA was noticed in obese children versus lean controls. The subcutaneous adipose tissue and not the visceral adipose tissue was correlated to the changes in PUFA and saturated FA, suggesting an abnormal essential FA metabolism in obese adolescents [39].

Fish oil is rich in EPA and DHA and has a hypotriglyceridemic effect in comparison to MUFA, but supplementation only with DHA does not share the hypotriglyceridemic effect. Fish may be more beneficial than fish oil supplementation. The favorable effect of cis-MUFA on cardiovascular diseases is unlikely, but of those n-3 PUFA is suggestive [19].

Omega-3 PUFA supplementation was associated with a reduced level for triglycerides and an up-regulated expression of the gene encoding peroxisome proliferator activated receptor-α (PPARα), a transcription factor that increases fatty acid oxidation and down-regulates proinflammatory genes [40].

Omega-3 fatty acids can prevent prediabetes and diabetes mellitus development because these PUFA are ligands for peroxisome proliferator receptor activator gamma (PPARγ) involved in insulin sensitivity and also, by constituting of the novel biologically active lipid mediators (resolvins and protectins), which also increase insulin sensitivity. The obesity-induced hepatic steatosis can be prevented by Omega-3 PUFA because they decrease endogenous lipid production by inhibiting the expression of the transcription factor, sterol response element binding protein-1c, SREBP-1c [41].

In accordance with the above molecular effects, beneficial effects of Omega-3 PUFA in obesity were demonstrated in clinical and experimental studies. It was shown that Omega-3 fatty acids prevent metabolic syndrome by reducing hepatic steatosis and visceral fat, by reducing serum triglycerides, and improving insulin sensitivity [42, 43].

Omega-3 fatty acids, by inhibiting hepatic lipogenesis, reduce a jéun and postprandial triglyceridemia [44] and improve the quality of platelets membrane phospholipids. In extrahepatic tissues, the activation of lipoprotein lipase has also a great contribution to the hypotriglyceridemic effect of Omega-3 fatty acids. They have also an antiatherogenic effect by reducing the quantity of small and dense LDL [45].

Many clinical and experimental studies have demonstrated that omega-3 PUFA have lipidlowering effects. The improvement in lipid profile is due mainly to enhanced fatty acid betaoxidation and suppression of fatty acid synthesis in the liver [46, 47, 48, 49].

During PUFA treatment, the gene expression of the lipogenesis enzyme sterol regulator element binding protein-1c (SREBP-1c) is decreased while the fatty acid oxidation in the liver is increased via the activation of peroxisome proliferator activated receptor-α (PPARα) [50, 51].

Dyslipidemia and insulin resistance are associated with non-alcoholic fatty liver disease (NAFLD). Diet rich in lipids and augmented lipolysis in adipose tissues increase the hepatic pool of fatty acids for the liver. Hyperglycaemia and hyperinsulinemia increase lipogenesis in the liver and contribute to hepatic steatosis [52, 53].

Omega-3 PUFA have beneficial effects in liver steatosis by decreasing triglyceridemia and by reducing the muscle intramyofibrillar triglycerides [51].

By upregulating the genes involved in insulin sensitivity, namely glucose transporters (GLUT-2/GLUT-4), peroxisome proliferator activated receptor-γ (PPAR-γ), and insulin receptor signaling (IRS-1/IRS-2) [41], Omega-3 PUFA increase insulin sensitivity.

Lipid intake should represent 25–35% of total energy intake. In USA, saturated FA represents 11% of total energy intake, PUFA 7%, and MUFA 12%. Excess consumption of fatty acids, above the intake recommended, lead to weight gain that is detrimental for body health [21].

When in the diet, saturated fatty acids and trans fatty acids are replaced by cis-MUFA and PUFA, plasma levels for total cholesterol and LDL-c are reduced, while HDL-c concentration remains unchanged. According to the value of the calculated atherogenic index (total choles‐ terol/HDL-c), this should mean a beneficial effect. Diets rich in cis-MUFA and PUFA may improve insulin sensitivity; and cis-MUFA compared with carbohydrate and saturated fatty acids reduced HOMA-IR values [19].

Omega-3 fatty acids can prevent prediabetes and diabetes mellitus development because these PUFA are ligands for peroxisome proliferator receptor activator gamma (PPARγ) involved in insulin sensitivity and also, by constituting of the novel biologically active lipid mediators (resolvins and protectins), which also increase insulin sensitivity. The obesity-induced hepatic steatosis can be prevented by Omega-3 PUFA because they decrease endogenous lipid production by inhibiting the expression of the transcription factor, sterol response element

In accordance with the above molecular effects, beneficial effects of Omega-3 PUFA in obesity were demonstrated in clinical and experimental studies. It was shown that Omega-3 fatty acids prevent metabolic syndrome by reducing hepatic steatosis and visceral fat, by reducing serum

Omega-3 fatty acids, by inhibiting hepatic lipogenesis, reduce a jéun and postprandial triglyceridemia [44] and improve the quality of platelets membrane phospholipids. In extrahepatic tissues, the activation of lipoprotein lipase has also a great contribution to the hypotriglyceridemic effect of Omega-3 fatty acids. They have also an antiatherogenic effect by

Many clinical and experimental studies have demonstrated that omega-3 PUFA have lipidlowering effects. The improvement in lipid profile is due mainly to enhanced fatty acid beta-

During PUFA treatment, the gene expression of the lipogenesis enzyme sterol regulator element binding protein-1c (SREBP-1c) is decreased while the fatty acid oxidation in the liver is increased via the activation of peroxisome proliferator activated receptor-α (PPAR-

Dyslipidemia and insulin resistance are associated with non-alcoholic fatty liver disease (NAFLD). Diet rich in lipids and augmented lipolysis in adipose tissues increase the hepatic pool of fatty acids for the liver. Hyperglycaemia and hyperinsulinemia increase lipogenesis in

Omega-3 PUFA have beneficial effects in liver steatosis by decreasing triglyceridemia and by

By upregulating the genes involved in insulin sensitivity, namely glucose transporters (GLUT-2/GLUT-4), peroxisome proliferator activated receptor-γ (PPAR-γ), and insulin

Lipid intake should represent 25–35% of total energy intake. In USA, saturated FA represents 11% of total energy intake, PUFA 7%, and MUFA 12%. Excess consumption of fatty acids, above the intake recommended, lead to weight gain that is detrimental for body health [21].

When in the diet, saturated fatty acids and trans fatty acids are replaced by cis-MUFA and PUFA, plasma levels for total cholesterol and LDL-c are reduced, while HDL-c concentration remains unchanged. According to the value of the calculated atherogenic index (total choles‐ terol/HDL-c), this should mean a beneficial effect. Diets rich in cis-MUFA and PUFA may

receptor signaling (IRS-1/IRS-2) [41], Omega-3 PUFA increase insulin sensitivity.

oxidation and suppression of fatty acid synthesis in the liver [46, 47, 48, 49].

binding protein-1c, SREBP-1c [41].

64 Lipoproteins - From Bench to Bedside

α) [50, 51].

triglycerides, and improving insulin sensitivity [42, 43].

reducing the quantity of small and dense LDL [45].

the liver and contribute to hepatic steatosis [52, 53].

reducing the muscle intramyofibrillar triglycerides [51].

When replacing carbohydrate and saturated fat, MUFA consumption can be beneficial. MUFA has positive impact on surrogate markers, but the potential impact on disease outcome remains unclear. When MUFA replaces saturated fatty acids it reduces total cholesterol and when MUFA replaces carbohydrates it decreases triglycerides and increases HDL [21].

Nowadays, the recommendation is to replace solid fats with oils rich in MUFA and PUFA and the most recommended diet is the Mediterranean diet. A randomized controlled trial done on 7,000 patients demonstrated that Mediterranean diet beats low-fat diet. In the study, the two groups of subjects with Mediterranean diet that were supplemented with either olive oil (approximately 4 tablespoons/day) or nuts (average of 3 servings/day) versus the group with low-fat diet reduced the risk for major cardiovascular events [54].
