Postprandial lipemia and cardiovascular diseases : the beneficial role of strength exercise

Development of cardiovascular diseases (CVD) has been linked with changes to the lipid profile that can be observed during the postprandial period, a phenomenon known as postprandial lipemia (PL). Physical exercise is currently the number one non-pharmacological intervention employed for prevention and reduction of risk factors for the development of CVD. This in turn has created a growing interest in the effects of physical exercise on regulation and equilibrium of lipid metabolism. In this review we compare the results of studies that have investigated the beneficial effects of strength training on PL. We analyzed articles identified in the PubMed, Scopus and EBSCO databases published from 1975 to 2013 in international journals. Studies were selected for review if they covered at least two of four keywords. The results of these studies lead to the conclusion that strength training is effective for reduction of postprandial lipemia because it increases baseline energy expenditure. This type of training can be prescribed as an important element in strategies to treat chronic diseases, such as atherosclerosis.

24 hours after a single bout of strength exercise. 6his mobilization and utilization of body fat can be particularly useful for reducing PL. 11 The purpose of this review was therefore to compare results in the literature on the effects of strength exercises on plasma lipoproteins in the postprandial period and their relationship with risk of cardiovascular disease.

METHODS
This article is based on a review of current references on the subject identified in PubMed, Scopus and EBSCO databases and published in international journals between 1975 and 2013.The database searches employed terms such as, strength training, resistance training, postprandial lipemia, cardiovascular diseases, volume and intensity.Articles were selected for the review if they addressed a combination of at least two of the four keywords of interest: strength training, lipoproteins, atherosclerotic plaque or lipoprotein lipase activity.

FORMATION, FUNCTION AND USE OF LIPOPROTEINS
Several important functions have been attributed to lipoproteins, including dissolving and transporting lipids, which are generally hydrophobic substances, from aqueous plasma.The main target lipids are the fatty acids, cholesterol and triglycerides (TAG).Triglycerides are the body's most important form of energy storage, are deposited in adipose and muscle tissues and consist of three fatty acids and one glycerol molecule. 12Cholesterol is a member of the group of fats that are essential for life, since it is used in the production of hormones, bile acids and cell membranes.Only 30% of the cholesterol present in the body comes from the diet, the remainder is synthesized and may be accumulated in arterial walls when in excess. 13Hypercholesterolemia may be secondary to dietary or genetic causes, and in most cases is the result of an unbalanced diet rich in saturated fats and a lack of physical activity.
Blood cholesterol is transported by lipoproteins.Several types of lipoproteins are known and these can be grouped into two sets: (a) TAG-rich, larger and less dense lipoproteins, represented by chylomicrons of intestinal origin (responsible for transporting lipids absorbed by the intestine from the diet and enterohepatic circulation), and very low density lipoproteins (VLDL) of hepatic origin; and (b) cholesterol-rich low density lipoproteins (LDL) and high density lipoproteins (HDL).There are also a class of intermediate density lipoproteins (IDL) and

INTRODUCTION
Changes to the lipid profile that represent a risk factor for development of cardiovascular diseases (CVD) are commonly observed during atherosclerotic plaque formation and the subsequent inflammatory response. 1,2Postprandial lipemia (PL) is a phenomenon that is known to induce endothelial dysfunction by increasing the availability of free fatty acids (FFA) and is often seen in sedentary or overweight individuals.A high β-oxidation rate induces accumulation of electrons followed by an increase in free radical production (e.g.superoxide radicals), which deviates the course of nitric oxide (NO) utilization, decreasing availability of this potent vasodilator and mediator of defense against atherosclerosis.Endothelial function deteriorates in the same proportion as lipemia increases, as in an acute response to systemic changes, whether chronic or postprandial. 3he phenomenon is associated with increased secretion of pro-inflammatory cytokines, expression of adhesion molecules (ICAM, VCAM-1) and prooxidative activity.The endothelial damage observed during this process promotes recruitment of injury-responsive cells by stimulating infiltration of monocytes to the subendothelial space, which differentiate into macrophages (foam cells), which are well-known to exhibit the ability to accumulate large amounts of lipids originating from cytoplasm-generating products that induce tissue damage and reactive oxygen and nitrogen species.Hypertriglyceridemia is a therefore a factor that can stimulate atherogenic potential. 46][7] This has led to growing interest in research into the effects of exercise on lipid metabolism. 2 Notwithstanding, little is yet known about the preventative effects of strength exercises on development of CVD, through changes in important risk factors such as PL.Strength training apparently reduces total cholesterol concentrations in adults. 8However, strength exercise is still used as an additional alternative to aerobic training. 9t is believed that, in common with aerobic exercise, strength exercise can help to reduce PL in response to increased lipoprotein lipase (LPL) activity (which is, for example, a key enzyme in triglyceride hydrolysis). 10Strength training also increases insulin sensitivity, 6 reduces plasma concentrations of fasting triglycerides (TAG) and markedly increases baseline fat oxidation for up to  lipoprotein (a) [Lp (a)], which is the result of covalent bonding of LDL particles to apo (a). 10,13rom the four classes of lipoproteins listed above, those that are most often assayed in order to test for dyslipidemias and determine whether there is a propensity to CVD are total cholesterol (TC), TAG, HDL cholesterol (HDL-c) and LDL cholesterol (LDL-c). 14Reference values for diagnosing dyslipidemias in adults over the age of 20 are shown in Table 1. 15igure 1 illustrates the mechanisms of blood TAG clearance, after strength training, and the sources supplying fatty acids.In the fasting state, after strength training, most of the fatty acids used to synthesize VLDL-TAG are derived from nonesterified fatty acids (NEFA) in the blood which originate from adipose tissue (1).Some fatty acids can also be derived from hepatic TAG droplets, although the relative contribution of this source is still unknown (2).In the fed state, VLDL synthesis is temporarily inhibited (about 1 hour) by the action of insulin.Release of NEFA could contribute to release of fatty acids in the postprandial state, but concentrations are low during the postprandial period due to the antilipolytic effect of insulin in adipose tissues (3).Finally, lipid remnants of chylomicron could provide large amounts of fatty acids to the liver, which could be esterified once more to VLDL and then secreted.The contribution of this source of VLDL-TAG has not yet been measured in humans (4).The same is true of de novo intestinal lipogenesis, supplying new fatty acids that become available for chylomicron and TAG production, but this process has not yet been measured. 10n the scientific literature, understanding the two mechanisms of TAG release is of paramount importance.The first is mediated by breakdown of fatty acids and their removal from TAGs and the particle-rich lipoproteins that circulate in the blood.Blood TAG reduction has been observed to be proportional to LPL activity. 13The second method of clearance of plasma TAG takes place when a triacylglycerol particle is absorbed in the liver by its receptor. 13hen consumed in excess, TAG tends to deposit on the walls of arteries and form fat plaques (atheroma), which can impair blood flow, stimulate clot production and contribute to narrowing of blood vessels, especially if plasma HDL-c is at low concentrations. 16

POSTPRANDIAL LIPEMIA AS A RISK FACTOR FOR DEVELOPMENT OF CVD
Postprandial lipemia can be defined as increased lipoprotein and chylomicron in acute response to a high-lipids meal which then return to baseline levels over time.This methodology has allowed us to trace a relationship between the effect of lipids meals and CVD in normal-weight individuals of both sexes.Measurements of FFA such as NEFA and TAG are often used to reflect PL, since TAG increases in a rapid and significant manner in response to food intake. 2 Postprandial lipemia measurement opens a new perspective for studies that aim to compare intervention methodologies for treatment and prevention of the deleterious effects of dyslipidemia. 17ilversmit, 1 proposed that atherogenesis is closely associated with the phenomenon of postprandial hyperlipemia, since experiments with animals and humans have shown that endothelial cells can pick up chylomicron remnants and LDL-c.Clinical studies have shown that the magnitude of postprandial lipemia or even elevated levels of postprandial TAG can predict symptomatic or asymptomatic atherosclerosis, independently of fasting analysis.
Epidemiologic studies, clinical trials and current scientific literature show that increasing PL is directly linked to the progression of atherosclerotic plaques, either through deposition of lipoprotein debris on the arterial surface or in an indirect manner with predominance of lipoproteins such as chylomicrons, VLDL and LDL-c. 18ostprandial lipemia is characterized by a state of hypertriglyceridemic transition and reflects an integrated measure of individual ability to remove TAG, the fasting concentrations of which, in turn, have been shown to be related to the size of LDL-c particles.This response can be subject to increased fatty acid mobilization, synthesis of VLDL-c and delays in its removal, providing greater interaction between lipoproteins and contributing to the formation of small dense particles of LDL-c, which are highly atherogenic.Therefore, interventions to attenuate postprandial lipid response can be considered beneficial to cardiovascular health. 5,10

TRAINING AND PROGRESSION OF ATHEROSCLEROTIC PLAQUES
Atherosclerosis is a multifactorial inflammatory disease arising from endothelial injury, mainly acting on the intimal layer of arteries with medium and large calibers. 19,20Atherosclerotic plaque formation begins with vascular wall aggression that occurs due to various risk factors such as high plasma lipoprotein levels (LDL, IDL, VLDL and chylomicron remnants), systemic arterial hypertension, dyslipidemia, obesity and smoking.After hydrolysis, chylomicron remnants may become atherogenic, especially if they penetrate to the arterial tissue. 21therosclerosis is also characterized by the arterial wall thickening that is seen as an accumulation of fat and collagen fibers.Atherogenesis and thickened growth occurs gradually through a process that involves endothelial injury, 4 tissue proliferation, infiltration and accumulation of lipids derived from plasma and tissue necrosis.Macrophages are intense inflammatory cells with lipid metabolism and are determinants of the development of atherosclerosis because they accumulate large quantities of cholesterol inside themselves. 22They have scavenger receptors that are specific for oxidized LDL (oxLDL), which is strongly associated with increased PL in coronary disease because of secretion of inflammatory mediators harmful to the endothelium.Lipid accumulations also stimulate these cells' secretory and proliferative capacity to increase, in a positive feedback process.Changes in lipid profile promote increased vascular stress, activating transcription factors essential for many intracellular signals of inflammatory response that are responsible, among other things, for inducing expression of adhesion molecules (ICAM, VCAM) and consequent increased infiltration of the endothelial layer by macrophages. 2dhesion molecules and classic inflammatory markers are observed after high-fat food intake.Gill and Hardman 5 reported a strong relationship between elevated fast plasma TAG and high levels of interleukin-6 (IL-6) and tumor necrosis factor alpha (TNF-α) in untrained subjects, but did not attempt to relate their results to endothelial dysfunction. 5arly stages of endothelial lesions and of atherosclerotic plaque formation can be observed even in later fetal development. 19Abnormal levels of TC, TAG, HDL-c, LDL-c and Lp (a) are also directly associated with genesis and progression of atherosclerosis. 1 Scientific evidence shows that for a given reduction of LDL-c there is a proportional reduction in the risk of coronary events, which were not associated with lipid values or absolute baseline risk. 2 This means that the absolute benefit of the intervention is directly related to the initial absolute risk of occurrence of events arising from CVD, such as sudden death and myocardial infarction itself. 23ver the last three decades, the hypothesis about the effect lipoproteins have in patients with CVD has been confirmed, showing that decreases in LDL-c plasma levels induced by exercise and increased lipoprotein lipase activity lead to reductions in mortality in patients at high risk of developing CVD. 9,13,23,24

EFFECTS OF PHYSICAL EXERCISE ON LIPOPROTEIN LIPASE ACTIVITY
Physical activity, both aerobic and strength training or a mixture of the two, in combination with a controlled diet can effectively prevent and improve obesity, hyperlipidemia and CVD, due to its effect in increasing lipoprotein lipase (LPL) enzyme activity. 24The LPL enzyme is found in the capillaries of adipose tissue, the heart and skeletal muscle.It is known to aid in the removal of blood chylomicrons and in catalyzing TAG to free fatty acids and glycerol.Lipoprotein lipase may also have an anchoring function, attaching chylomicron remnants to the liver wall, where the re-esterification process occurs. 25In adipose tissues and skeletal muscle, LPL activity is regulated in a dependent manner (i.e.increased LPL activity in one type of tissue is closely associated with a decrease in the LPL activity of the other).Insulin release attenuates the LPL activity of skeletal muscle, but potentiates its activity in adipose tissues, which is important during fasting periods. 11,24The activity of LPL is elevated by exercise, especially in the recovery period after one bout of strength exercise.

EFFECTS OF STRENGTH TRAINING ON POSTPRANDIAL LIPEMIA
Aerobic exercise performed between 15 and 18 hours prior to ingestion of a high fat meal may attenuate PL response. 5The energy expended during aerobic exercise is an important factor in inducing PL reduction. 7Few studies have evaluated the influence of strength exercises on PL. 9,11,24,26,27 Notwithstanding, strength exercise is widely recommended by health associations to improve quality of life and weight management and for prevention of several diseases. 20o our knowledge, only five studies 9,11,24,26,27 have analyzed the influence of the main strength training variables such as volume (number of sets) on PL.Furthermore, these studies contradict each other, and when comparing different volumes only one study 24 reported an acute reduction in PL concentrations.In contrast, three studies 11,26,27 failed to observe any reduction in PL after a single session of strength exercises.
Only one study 11 examined the dose-response characteristics of three different volumes of strength exercises on PL (one, three and five sets of ten maximum repetitions, plus a control group that did not exercise), finding no significant difference between doses.However, experimental subjects consumed more energy and fat than the control group the night before the fat tolerance test.This may have increased the possibility that modifying the diet was a confounding factor masking the effect of strength training on glycemic response.It would therefore be interesting to examine the effect of different doses of strength training on PL without suppressing exercise-related events, including energy deficit and physiological, metabolic and hormonal disturbances.Moreover, the authors of that study 11 based their results on a mixed sample of men and women, but reported different PL responses between the sexes.
Singhal et al. 9 have evaluated the effect of different intensities of strength exercises in PL using moderate (60-65% of 1RM, p=0.052) and high intensities (85-90 % of 1RM, p=0.014).Indeed, it seems that multiple series at moderate intensity, 9 when compared with multiple series 21 at high intensity, 9 substantially reduce the total time and muscular recovery period followed by lower plasma concentrations of CRP, TNF-α and IL-6. 25otwithstanding, several studies indicate that multiple sets are superior to single series of exercise in terms of neuromuscular and morphological adaptations, although little is known about the metabolic and biochemical changes that occur in response to different volumes and intensities of strength training. 9n view of the contradictory results described above, the effects of strength training on PL requires further investigation.We did not find any studies that have investigated the effects of different volumes before and after strength training.Zafeiridis et al. 21nvestigated the effects of strength training on TAG response in the postprandial period and observed a reduction in PL with a six-hour protocol and a reduction in the total area under the TAG curve after conducting a session of strength training.The protocol included an energy intake of 0.76 or 1.40 MJ depending on exercise intensity.The same author recently completed a study that evaluated the effects of an aerobic exercise protocol and a strength exercise protocol in which they evaluated total estimated energy expenditure at 5.1 MJ and observed decreases of 12% and 18% respectively on the total elementary AUC of plasma PL.The evidence on this topic is still confused, since there is one study that disagrees with these results.Petitt et al. 24 observed a reduction in PL concentrations after a single session of strength exercises, with energy expenditure estimated at 1.7 MJ.The main results of the aforementioned studies are presented in Table 2.

STRENGTH TRAINING AND CARDIOVASCULAR DISEASE (CVD)
Strength training is known to be a strong inducer of changes in neuromuscular, morphological and metabolic conditions.Adaptations found during this period of strength training have been associated with a protective effect including reduced mortality and incidence of metabolic syndrome. 24Evidence from epidemiological studies shows that there is a relationship between reduced risk of coronary heart diseases and regular participation in strength training. 18,21affenbarger and Hale 28 investigated the effects of occupational activity on the development of CVD in dockers.Dockworkers who performed hard physical labor, such as lifting and loading of heavy loads, had a lower mortality rate for coronary heart disease when compared to dockers who did not perform strenuous physical tasks.In another study about the effect of strength training on cardiovascular responses, Tanasescu et al., 29 found that individuals who performed 30 minutes of strength exercises per week were at 23% lower risk of developing coronary heart disease than individuals who did not perform any weight training.However, the benefits of strength exercise on risk factors for development of cardiac diseases are not well established.
Cardiovascular diseases share a common pathophysiology involving atherosclerosis and thrombosis. 9,29Disorders of lipoprotein metabolism during the postprandial period can promote atherosclerosis due to accumulation of LDL-c and VLDL remnants in plasma after catabolism of these lipoproteins, which increases susceptibility to oxidation of these particles. 13therosclerosis is a disease that is not only characterized by lipid accumulation, but also by a chronic inflammatory process. 27C-reactive protein (CRP) is a classic marker of the inflammatory process associated with atherosclerosis that can also play an etiologic role in atherogenesis.Epidemiological research by Paffenbarger and Hale, 28 suggests that strength work is beneficial to health, and it is possible that the energy expenditure incurred in this effort provides some cardioprotective effects.It therefore remains important to determine how much strength exercise is beneficial to cardiovascular health, mainly for specific populations.

CONCLUSIONS
This review supports the hypothesis that resistance exercise has a direct relationship with changes in postprandial lipemia that are associated with cardiovascular disease.However, few studies have looked at the effects of this intervention on changes in the lipid profile after fasting or after a high-fat meal.
Strength training proved more effective than aerobic exercise for reducing PL concentrations by increasing resting energy expenditure without necessarily correlating with changes in body composition.Indeed, strength training appears to be a crucial tool for improving lipid parameters through greater efficiency of energy demand, and can therefore be considered an important non-pharmacological strategy for reducing risk factors for development of CVD.

Figure 1 .
Figure 1.Origin of triglycerides (TG) from exogenous and endogenous lipoproteins and the release mechanisms of triglyceriderich lipoproteins in plasma, baseline state and after strength training.(FA-fatty acid, LPL-lipoprotein lipase; NEFA-non-esterified fatty acids, VLDL-very low density lipoprotein).

Table 1 .
15ference values for diagnosis of dyslipidemia in adults over the age of 20 (adapted from Pearson et al.15).

Table 2 .
21thods and results of studies reporting the effects of strength exercise on PL (adapted from Zafeiridis et al.21).