INTRODUCTION

Fat and carbohydrates provide the most important form of fuel for exercise and sport activities. During exercise, there are four major endogenous sources of energy: plasma glucose derived from liver glycogenolysis, free fatty acids (FFAs) released from adipose tissue lipolysis and from the hydrolysis of triacylglycerol (TG) in very low-density lipoproteins (VLDL-TG), and muscle glycogen and intramyocellular triacylglycerols (IMTGs) available within the skeletal muscle fibers. Fats and carbohydrates are oxidized simultaneously, but their relative utilization as fuel sources during physical activity is influenced by a variety of factors, including the type of exercise, exercise duration, and intensity. The index that establishes the training load is the V̇o_2max, which is the maximum amount of oxygen that can be used in the unit of time by an individual. At a low-to-moderate intensity, as well as during prolonged exercise, most of the energy requirements for skeletal muscle can be met from predominantly FA oxidation, with a small contribution from glucose oxidation. The total use of fats increases until the intensity of the exercise reaches ~60–65% V̇o_2max (1–3) and 74% of the maximum heart rate (1). The increase in exercise intensity causes a shift in the mobilization and use of the energy substrate. An increase in the relative contribution of carbohydrate oxidation to energy expenditure and a parallel decrease in the relative contribution of fat oxidation occur during the transition from moderate- to high-intensity exercise (12, 92). The source of FA also changes during exercise: at 25% of V̇o_2max, the oxidized fat derives from plasma FA (48, 62, 92); at 65% of V̇o_2max, the contribution of plasma FA decreases and the rate of IMTG oxidation increases and provides about half of the FA used for total fat oxidation (74, 92, 107). During mild- or moderate-intensity exercise, the increased request of FA is provided by increased lipolysis of adipose tissue TGs (62, 110). Such increase of adipose tissue TG lipolysis and, presumably, IMTG, is mediated by increased catecholamine response to exercise (6). Exercise training has implications in the improvement of glycemic control in patients with type 2 diabetes mellitus and insulin sensitivity and resistance (9, 42) and in the prevention of multiple sclerosis, lung diseases, Parkinson’s disease, and cardiovascular diseases (31, 82). Physical activity is associated with reduced cardiovascular morbidity and mortality (21, 35, 81) and is recommended for treatment of hyperlipidemia, which is known for being a risk of coronary heart disease (CHD) (17, 66). In fact, among the risk factors for CHD, along with hypertension, diabetes, smoking, and obesity, both low-density lipoprotein-cholesterol (LDL-C) and high-density lipoprotein-cholesterol (HDL-C) are also reported (Hajar, 2017). Lipoproteins, which are mixed micellar-like particles, include protein components called apolipoproteins (Apos). Apos have structural and regulatory roles, such as modifying receptor uptake and the activity of enzymes involved in lipoprotein metabolism (32). Given the additional advantages Apos possess [i.e., fasting samples are not required, the ratio of ApoB to ApoA1 (ApoB/ApoA1) is a better index of the adequacy of statin therapy than LDL-C, and the measurements of ApoB and ApoA1 are standardized, whereas LDL-C and HDL-C are not], there would appear to be considerable advantage to integrating Apos into clinical practice (97). Furthermore, the measurement of the ApoB and ApoB/ApoA1, which represents the balance between proatherogenic and antiatherogenic lipoproteins, is the best variable to quantitate coronary risk (93).

In this review, we report studies that have examined the relationship between exercise and commonly measured CHD biomarkers together with the effects of physical training on changes in plasma ApoB and ApoA1 as well as in light of various causes of heterogeneity, such as age, sex, lifestyle, obesity, and diabetes.

BLOOD LIPID TRANSPORT AND CARDIOVASCULAR RISK

Long-chain FA are absorbed in duodenum and transformed into TGs, that, together with cholesterol (C) and proteins, are assembled as chylomicrons for blood transport. Short- and medium-chain FA diffuse into the blood and are transported to the liver through the hepatic portal vein bound to albumin. TG and C are transported by four main classes of lipoproteins: very low-density lipoproteins (VLDLs) rich in TG, chylomicrons, low-density lipoproteins (LDLs) rich in C, and high-density lipoproteins (HDLs). Chylomicrons also deliver dietary C to the liver, whereas VLDLs are LDL precursors derived from their catabolism (7). HDLs are essential in plasma lipid transport, providing to the metabolism of chylomicrons and VLDL and removing the excess of unesterified C from these lipoproteins. Moreover, HDLs are involved in a process known as “reverse C transport,” taking care of the C transport from peripheral cells to the liver to favor its excretion and catabolism (77). HDL is formed by the aggregation of the various components of a lipoprotein: C, TG, apolipoproteins, and phospholipids. The concentration, composition, shape, and size of plasma HDL are determined by numerous proteins influencing biogenesis, remodeling, and catabolism (119). In particular, the liver and small intestine secrete the apolipoprotein ApoA1. The fusion of these components (nonesterified C, ApoA1, ApoC2, ApoE) forms an initial HDL, called HDL3 (77). The nonesterified HDL3-C is esterified by the enzyme lecithin-C acyltransferase; therefore, it is named HDL2 and contains predominantly esterified C and a small extent of TG (Fig. 1). These lipoproteins go to the liver, which breaks down the TG into monoacylglycerol and FFA and then endocytes them (77). VLDLs are assembled in the liver and directly released into the bloodstream. Within the hepatocyte, FAs are esterified to glycerol-3-phosphate and to C to generate TG or cholesteryl esters, respectively. Therefore, chylomicrons and VLDL are mainly deputed to the transport of TG taken with the diet and of hepatic origin, respectively, exploited as a source of energy to tissues or for storage in adipose tissue. Once in plasma, VLDLs interact with lipoprotein lipase (LPL). LPL is an enzyme present on the extracytosolic part of the cells in several tissues of the body, but in particular on the capillary endothelium, causing the hydrolysis of the TG and the consequent release of FFA. During fasting and fed state, VLDLs are the main source of circulating endogenous TG but not the principal source of potential energy during exercise; in fact, VLDLs are rapidly converted to intermediate-density lipoproteins (IDLs) and low-density lipoproteins (LDLs) that contain low levels of TG (5, 7, 13, 87) (Fig. 1). Epidemiologic studies have identified an important inverse relationship between plasma HDL content and the onset of CHD (4, 98).

Atherosclerosis is a disease caused by several factors and occurring in multiple stages; it is a cause of heart attack and stroke and consists of the initial endothelial cell injury followed by lipoprotein deposition, inflammatory reaction, and smooth muscle cell cap formation (69, 113). Oxidized LDLs (oxLDLs) in arterial walls, generated by reactive oxygen species and nitrogen species produced by endothelial cells (67) or by enzymes as leukocyte-derived myeloperoxidase (MPO) and vascular peroxidase-1 (VPO1) (113), are considered a significant cause of atherosclerosis pathogenesis. Moreover, macrophage “scavenger” receptors recognize oxLDLs promoting macrophage differentiation into foam cells leading to atherosclerosis (118). CD36, a scavenger receptor able to recognize modified LDL through multiple binding sites for FAs, is also associated with cardiovascular risk factors in young subjects (55, 86). In addition to CD36, other scavenger receptors are related to oxLDL recognition, such as SR-AI/II, SR-BI, macrosialin/CD68, LOX-1, and SREC (25). Treatments of hypercholesterolemic animals with potent antioxidant drugs showed a decrement in atherosclerotic process progression, proving that LDL oxidation may well be one of the atherosclerosis causes (105).

HDL has been underscored as a predictor of both prevalence and severity of atherosclerosis (98). HDLs remove C and fats from cells but also from atheroma of the arterial wall, allowing liver excretion or reutilization; for this reason, C contained within HDL (HDL-C) is sometimes labeled as “good C.” Finally, HDL blood concentrations above 60 mg/dL seem to have a protective effect against atherosclerosis and are related to the decrease in the incidence of CHD (4). It was demonstrated that ApoB is a more reliable indicator of circulating LDL particle number and cardiovascular risk than low-density lipoprotein-C (LDL-C). Because ApoA1 has antiatherogenic properties, ApoB/ApoA1 is associated with CHD risk (22, 117). ApoB exists in two isoforms, ApoB100 and ApoB48. Besides being predictive of atherosclerosis, the formation of HDL is a factor determining cardiac fitness. Adenosine triphosphate-binding cassette transporters (ABCA1, ABCG1, ABCG4, ABCG5, and ABCG8), ApoA1, and lecithin:cholesterol acyltransferase (LCAT) are involved in HDL biogenesis (84). The reverse C transport is mediated by peroxisome proliferator-activated receptor γ (PPARγ) and liver X receptors (LXRα/β) in a pathway that influences ABC carriers (52, 84). In particular, ABCA1 transfers C from macrophages to the specific lipid-poor C acceptor ApoA1. An excess of C enhances ABCA1 expression in macrophages (19). Hussein et al. (52) observed that a high level of glucose decreased LXR-dependent ABCA1 mRNA and protein levels, bringing to a defect in ABCA1-mediated efflux of ApoA1 to macrophages. A key enzyme with antiatherogenic property involved in reverse C transport is the lecithin:cholesterol acyltransferase (LCAT) that catalyzes the esterification of free C in plasma lipoproteins, therefore allowing HDL maturation (16, 80) (Fig. 1). In animal models, loss of LCAT activity enhanced the development of proatherogenic dyslipidemia and atherosclerotic lesion formation (27). In humans, however, the mutation of the LCAT gene has been related to both an increase (28, 50) and a decrease (15) in the carotid atherosclerosis process. Some studies also support the hypothesis that increased LCAT activity may be associated with increased formation of TG-rich lipoproteins leading to a reduction in LDL particle size (102, 114). This is of particular interest, as the different LDL subclasses have a different atherogenic capacity. Small and dense LDLs are more atherogenic than larger LDL subfractions because of their ability to cross the walls of the arteries, thus becoming a C resource capable of promoting the development of atherosclerotic plaque (54). The retention of atherogenic lipoproteins in the artery wall is a crucial event that can mark the beginning of the atherogenic process, according to the “response to retention” hypothesis (109). The accumulation of LDL in the arterial intima-media could be due to the interaction between ApoB-containing lipoprotein and proteoglycans. The affinity of ApoB-100 lipoproteins for arterial proteoglycans and glycosaminoglycans could be associated with clinical manifestations of atherosclerosis and exploited as biomarkers of CHD (51). Generally speaking, HDL is also of considerable importance in metabolic syndrome and insulin resistance. Gobato et al. (37) observed that various body composition indicators, metabolic syndrome, and HDL showed correlation with insulin resistance. In the clinical scenario, the TG-to-HDL ratio (TG/HDL) has been proved to have a high correlation with prevalence of insulin resistance and metabolic syndrome, one of the most prevalent risk factors for atherothrombotic disease in the nonobese and normoglycemic women (44). TG/HDL has also been proposed as a simple marker of insulin resistance (20, 46, 60, 76, 85, 89). The potential utility of TG/HDL to detect insulin resistance was first reported by McLaughlin in a Caucasian population (76). Similar results were found in different racial groups, such as Korean (58), non-Hispanic Black, and Mexican American (68). TG/HDL was also associated with insulin resistance in Chinese patients with newly diagnosed type 2 diabetes mellitus (91). However, this association may be ethnicity dependent inasmuch as studies showed that TG/HDL might not be a marker of insulin resistance for African populations (11, 59, 90, 100). Lowering the TG/HDL could assist in the prevention of diabetes for older adults because it was found that time-dependent TG/HDL ratios were positively associated with the risk of type 2 diabetes mellitus (120). Finally, dysfunctional HDL is one of the mechanisms of increased CHD risk in diabetes mellitus. This can be due to an alteration of components supporting HDL function in C efflux and LDL oxidation. The dampening of reverse C transport leads to increased risk of cardiovascular disease in diabetic patients (99).

THE RELATIONSHIP BETWEEN EXERCISE TRAINING, LIPID METABOLISM, AND CHD

A selection of articles included in the review are summarized in Table 1.

LIPOPROTEIN VARIATIONS DUE TO EXERCISE TRAINING

Plasmatic LDLs are thought to be atherogenic and the HDL antiatherogenic, with the ratio of non-HDL-C to HDL-C playing an important role in the risk and progression of CHD (116). The size of LDL particles can be influenced by genetic factors, diet, and also by lifestyle, such as physical activity (8, 18); thus, in primary prevention, physical activity could be a way to control CHD risk factors. The effects of the exercise are probably mediated by modifications in the activities of enzymes such as LCAT, lipoprotein lipase (LPL), and hepatic-triglyceride lipase (HTGL) implicated in the synthesis, transport, and catabolism of lipoproteins. Thus, exercise-induced lipid utilization is influenced by adipose tissue and intramuscular TG lipolysis, delivery of FA to the exercising muscle, regulation of FA transmembrane transport in muscle cells, and mitochondrial metabolism (56). Heath et al. (45) showed that when the effects of endurance exercise training on plasma lipoproteins were determined in 10 men (ages 46–62 yr), “antiatherogenic” benefits of exercise training were found. Training was at 50–85% of V̇o_2max, for 3–5 days/wk for 29 ± 7 wk. Training significantly increased HDL-C levels and the ratio of HDL-C to LDL-C (HDL-C/LDL-C) and decreased plasma C, LDL-C, and TG concentrations. Benefits seem to be due to the training program because they correlated well with changes in V̇o_2max (45). Also, in healthy persons as well as in patients with ischemic heart disease, diabetes, and renal failure, endurance activity with moderate intensity induced positive lipoprotein changes (43). Results from a first longitudinal study (38) investigating changes in lipid and lipoprotein levels in men and women after 16 wk of a strength-training program showed in women a decrement in C (−9.5%), LDL-C (−17.9%), and TG (−28.3%) concentrations. The ratios of total cholesterol (TC) to HDL-C (TC/HDL-C) and LDL-C to HDL-C (LDL-C/HDL-C) were also decreased (−14.3% and −20.3%, respectively). Among men, LDL-C decreased by 16.2%, whereas TC/HDL-C and LDL-C/HDL-C decreased by 21.6% and 28.9%, respectively. According to their lipid profiles, the women in the Goldberg study were of low coronary risk, of normal body weight, and younger with respect to subjects of another study, who were also at low coronary artery disease risk but middle-aged and obese (72). In the latter study, no changes in lipid profile of 16 sedentary obese women were seen after 12 wk of endurance training (72). Goldberg’s study showed no statistically significant change in HDL-C, but its trend was toward increased HDL-C levels, whereas Manning’s showed a decreasing trend (−8%), but it was not statistically significant. These conflicting findings may suggest that the effects of an endurance training program on TC, TG, LDL-C, and TC/HDL-C may depend on the length of the training period or to other uncontrollable factors. Interestingly, an analysis of many longitudinal studies indicated that women with elevated pre-exercise C concentrations responded most favorably to exercise training, thus suggesting its beneficial effects especially for women at risk for heart diseases (70). Taylor et al. (103) assessed multiple cardiovascular risk factors and observed that runners exhibited lower body mass index, C-reactive protein, TG, and non-HDL-C and higher HDL-C than controls (103). Greene et al. (39) analyzed serum lipid and lipoprotein levels after acute exercise (70% of V̇o_2max), followed by 12 wk of endurance exercise training in overweight and obese men and women. Training increased HDL-C (+9%) and HDL2b-C (+16%) concentrations in men. No change in HDL-C was found in women, but subfractions shifted from HDL3-C (−13%) to HDL2a-C (+25%) and HDL2b-C (+15%). Furthermore, in women LDL3-C concentration was lower after training (−6%). Finally, acute exercise decreased TC/HDL-C in overweight and obese men (39). Ratajczak et al. (88) studied the effects of 3-mo endurance and endurance–strength training programs, showing that both led to the improvement of lipid metabolism in 34 obese women. A significant decrement in TC (−6.2%) and an increment in HDL-C (+9.1%) after endurance training were found; in the group undergoing endurance–strength training, HDL-C increased (+8.5%) (88). Furthermore, Fontana et al. (34) showed that fat loss induced by increased energy expenditure due to exercise had different effects on CHD risk factors in 18 nonobese subjects. Specifically, exercise decreased LDL-C (−16.8%), whereas HDL-C increased, although not significantly. The TC/HDL-C decreased (−13.5%) significantly. Surprisingly, the plasma TG concentration was not decreased. In this group, a significant decrement in insulin resistance (homeostatic model assessment of insulin resistance score decreased by 33%) and a decrement (−17%), although not significant, in C-reactive protein were also observed. Yoshida et al. (115) demonstrated that exercise induced a significant reduction in LDL levels (−11%) after 8–16 wk, independently from moderate-intensity or high-intensity exercise programs. The group of participants suffered from moderate dyslipidemia, and this result may have come from the reduction of body weight. Similarly, Halverstadt et al. (40) reported that after 14 wk of moderate-intensity endurance exercise LDL levels slightly lowered (−0,5%), although this may have been due to a positive effect in controlling the diet and the quantity of fat ingested during the study. To confirm this, a study showed, independently from moderate- to high-intensity exercise, significant changes in LDL in the group with dietary modifications compared with the group that performed exercise alone. Therefore, to obtain important favorable effects, it is recommended to combine the exercise with lifestyle changes (79). Weiss et al. (2016) conducted a randomized intervention trial on overweight sedentary men and women to evaluate the benefits after caloric restriction, endurance exercise training, or the combination of both. Beneficial effects against CHD risk in all three cases were substantial: decreases of systolic and diastolic blood pressure, total C (−5 to −12%), non-HDL-C (−8 to −15%), TG (−4 to −31%), and glucose (−2 to −5%); no changes were observed for HDL-C, C-reactive protein, carotid–femoral pulse wave velocity, and carotid augmentation index. However, the effects were not additive when weight loss is matched. The study by Kłapcińska et al. (61) showed that TG and the ratios of LDL to HDL (LDL/HDL), TC to HDL (TC/HDL), and TG to HDL (TG/HDL), together with plasmatic atherogenic burden, decreased significantly after the first 12 and 24 h of running (TG −60%; LDL/HDL −26%; TC/HDL −24%; TG/HDL −75%), levels that persisted for 48 h after the run, and a progressive increase in the level of HDL-C (+13 to +26%) during the run with a return to the baseline 48 h after. Although the serum concentration of HDL-C positively correlated with the distance covered during the run, TG, TC, LDL-C, TC/HDL-C, LDL-C/HDL-C, and the ratio of TG to HDL-C (TG/HDL-C) were negatively correlated. Decrement in TC/HDL-C, LDL-C/HDL-C, and TG/HDL-C and in the atherogenic index found during the run showed opposite trends during recovery (61). In another study (112), the changes in lipid metabolism in ultramarathon runners were analyzed. The TG, LDL-C, and TC/HDL-C were lower immediately after the run (TG −30%; LDL-C −8%; TC/HDL-C −8%); then, TG level and the ratio of TC to LDL-C returned to baseline 2 days after the race, and LDL-C values returned to baseline 9 days after the race. C was significantly lower only on the second day after the competition (−15%). Finally, HDL-C increased immediately after the race (+5%) and was found to have decreased 2 and 9 days after the race (112). It has also been seen that regular physical activity increases LDL-C particle sizes (108) reducing the atherogenicity, although a study by Elosua et al. (29) showed that aerobic exercise in healthy sedentary individuals had no effect on LDL particle diameter. The study by Holme et al. (49) included an exercise program extended for longer periods, relative to other studies, in overweight healthy men; it was found that the exercise program significantly influenced LDL levels (49). Therefore, to induce changes in blood lipoproteins in general and LDL in particular, Kraus et al. (63) studied the effects of a moderate-intensity exercise regimen in 111 sedentary overweight participants with mild-to-moderate dyslipidemia, randomized into 3 groups of aerobic exercises. It was found that the beneficial effects on the lipoprotein profile were not related to exercise intensity but to the amount of activity (63). Butcher et al. (14) showed that low-intensity exercise modulates lipid metabolism together with the transcription factors PPARγ and LXRα responsible for controlling reverse C transport. PPARγ, LXRα, and transporters ABCA1 and ABCG1 expression also enhanced after low-density exercise (14). Ghanbari-Niaki et al. (36) investigated ABCA1 expression, plasma lipids, and lipoprotein levels in response to a single session of circuit-resistance exercise in 20 female students and randomly assigned to control, 40%, 60%, and 80% of the individual one-repetition maximum groups. It was found that a single session of circuit-resistance exercise increased lymphocyte ABAC1 mRNA expression in all given exercise intensities and decreased VLDL-C (−12.5%). Conversely, changes in plasma HDL-C, LDL-C, and TC concentrations were not significant (36). Congruent results were also obtained in animal models by Rahmati-Ahmadabad et al. (83) that investigated the effects of high-intensity interval training on reverse C transport in 20 adult male Wistar rats. A significant increase of ABCA1 mRNA in liver and intestine after training and an increase of ABCG1 and LXR in liver but not in intestine, together with an increase in plasma LCAT and HDL, were detected. Furthermore, they showed that both high-intensity interval training (18 min) and moderate-intensity continuous training (1 h) significantly improved heart ABCA1, ABCG1, ABCG4, ABCG5, ABCG8, LXR-α, and PPARγ gene expression as well as plasma ApoA1, LCAT, lipids, and lipoproteins in rats subjected to high-fat diet (84).

The exercise, starting from moderate occupational energy expenditure, seems to have an important effect on Apos, lowering concentration of serum TG and increasing HDL in a healthy female population in China (71).

ApoS VARIATIONS DUE TO EXERCISE TRAINING

ApoB and ApoB/ApoA1, correlated to atherogenic and antiatherogenic lipoproteins, respectively, have been used as surrogate markers of the risk of CHD related to lipoproteins (75). Various studies have been published concerning not only the lipoproteins, but also the Apos present in the blood of subjects engaged in various training programs in an attempt to highlight their relationship with the risk of CHD. Rather than measuring C/lipoproteins levels, Apos assessment seems more relevant to evaluate the exercise training effects. More physically active people seem to have lower TG and VLDL concentrations and higher HDL particles, thanks to the greater concentrations of HDL2 and ApoA1 subfractions (43). Hoang et al. (47) found that more physically active men had higher concentrations of plasma ApoA1 (+10.8%) and preβ1-HDL (+92%) together with higher leukocyte ABCA1 expression (+61%). In a study published in 1991, Blumenthal et al. (10) showed the effects of aerobic exercise on lipid levels in pre- and postmenopausal women (average age 50 yr). Women were randomly assigned 12 wk of aerobic exercise (walking and jogging) or nonaerobic strength exercise (Nautilus circuit training). In all women, a slight reduction in HDL-C (−3%) and TC (−3%) and an increment of ApoA1 (+6%) and the ratio of ApoA1 to ApoB were observed. It was found that the aerobic group tended to express lower levels of ApoA2 (−10.6%) and consequently a higher ratio of ApoA1 to ApoA2 (+8%). Pre- and postmenopausal women modified their aerobic capacity and lipid levels with physical exercise; the short-term effects of aerobic and nonaerobic exercise on lipid profiles were similar in both groups (10). In a study of Kumagai et al. (64), 10 premenopausal obese women (32–49 yr), who had never smoked or regularly drunk alcohol, underwent training at an intensity of lactate threshold for 6 mo (3 times per week for 60 min using a cycle ergometer). After training, a significative reduction in body weight (−4.1 kg), an increase in V̇o_2max (+3.4 mL·kg⁻¹·min⁻¹), a significant increase in HDL-C (+8%) and HDL3-C (+6%), and a decrease in ApoB (−5%) and TC/HDL-C (−7%) were found. Conversely, TC, TG, HDL2-C, and ApoA1 levels did not change (64). Some endurance training studies in men showed that the ApoA1 level increased because of aerobic training (23, 57). Others did not find changes in ApoA1 levels (53) even after 1 yr of aerobic training (24, 111). These discrepancies may well be due to exercise session duration, regardless of intensity, and recruited subjects’ basal training status. In fact, no differences in ApoA1, ApoA2, and ApoB or in HDL-C and even its subfractions HDL2-C and HDL3-C were observed in 10 well-trained runners performing treadmill exercise on a high-intensity session (75% of V̇o_2max) for 60 min and a low-intensity session (50% of V̇o_2max) for 90 min (24). It is also possible that the lack of significance in some studies may be due to the smallness of the samples, which would have underestimated the influence of exercise on plasma lipoprotein levels. Indeed, a 1-yr open randomized study of a total of 188 middle-aged men (45 on a diet, 48 on exercise, 58 on a diet plus exercise and, finally, 37 on control) showed that exercise decreases ApoB concentration (−7.4%) and ApoB/ApoA1 (−10.8%) compared with nonexercise control group; consequently, LDL-C/HDL-C decreases (−13.8%) (49). In a study performed on 14 patients affected by CHD, results indicated that an 8-mo training program composed of two strength and two aerobic training sessions induces favorable metabolic adaptations: TC and TG levels decreased (−9.4% and −18.6%, respectively) and ApoA1 levels increased (+11.2%). Such adaptations protect patients with CHD; however, after 3 mo of resting, the health effects were reversed, underlining the importance of exercise in everyday life (104). Because lipid shift to HDL is essential for reverse C transport and has atheroprotective functions, Vaisberg et al. (106) investigated the transfer to HDL of the four main lipids in the circulation (esterified C, nonesterified C, TG, and phospholipids) caused by a high-intensity exercise. In vitro shift to HDL of the four lipids, together with plasmatic Apos and cytokine levels, was therefore assessed in 28 sedentary individuals and in 14 marathon runners before, immediately after, and 72 h after a marathon. In runners and sedentary individuals, LDL-C, ApoB, and TG concentrations did not change, whereas HDL-C and ApoA1 concentrations were higher in marathon runners (+42% and +13%, respectively). In marathon runners, ApoB and TG levels increased immediately after the marathon (+12% and +62%, respectively). Lipid shifts to HDL of phospholipids, TG, and nonesterified C were higher in marathon runners. Such lipid shifts decreased immediately after the marathon and returned to baseline values 72 h later. Also, IL-6 and TNF-α secretions were only momentarily stimulated by high-intensity exercise (106). Additionally, in runners, a broad reduction in ApoB levels and an increase in the ratio of LDL to ApoB were observed, directly proportional to the distance traveled, suggesting an acute positive change in the phenotype of LDL molecules (30, 65, 73, 78, 95).

In various studies, many occasional factors such as smoking, total fat loss, adherence to exercise, diseases, and supervised exercise specialist were not taken into account. Some of these factors can influence lipoproteins, mainly LDL (41, 94, 96, 101). Also, the individual characteristics of body composition and metabolic health at baseline may explain interindividual variation in HDL-C concentrations in response to training. Interestingly, a study by Diniz et al. (26) in postmenopausal women showed that the positive responders to training had 11% less HDL-C at baseline than negative responders (26). Furthermore, it is conceivable that the results may have been influenced by the fact that the people included in the studies came from various socioeconomic, cultural, and educational backgrounds. Nevertheless, these studies provide a perspective on the presence of correlations between low- to moderate-intensity exercise and changes in plasma lipoprotein levels. Despite some conflicting results, regular aerobic exercise of moderate intensity should be recommended to sedentary individuals to prevent the risks of cardiovascular disease.

CONCLUSIONS

In humans, CHD is the leading cause of morbidity and mortality. Among the traditional risk factors for CHD, along with hypertension, diabetes, smoking, and obesity, high LDL-C and low HDL-C are also included. Several studies confirmed the beneficial effects of endurance training on serum lipid profile with general TG decrement associated with significant reduction in TC and LDL-C and a significant rise in HDL-C. Furthermore, a minimum exercise threshold (65–80% V̇o_2max) can produce effects on serum lipids, despite these changes being minimal. The major positive change is in regard to HDL-C and TG, which increased and decreased, respectively (33). Changes in lipid metabolism caused by moderate exercise training are shown in Fig. 1. Furthermore, after an aerobic exercise an increase of ApoA1 has also been described, whereas an ApoB decrement after endurance exercise is often reported. Thus, ApoB/ApoA1 could be a better risk predictor of CHD than LDL/HDL. People subjected to good resistance training meet enzymatic and hormonal changes having a notable role in the mobilization of the sources of energy during prolonged exercise. Changes in lipid metabolism caused by moderate exercise training have healthy effects on cardiovascular system, but the mechanisms at the base of the protective effects of exercise still remain to be fully understood.

GRANTS

This study was supported by Italian Ministry of Education, University and Research Grant FFABR_ANVUR_20/2018.

DISCLOSURES

No conflicts of interest, financial or otherwise, are declared by the authors.

AUTHOR CONTRIBUTIONS

A.M. and S.M. conceived and designed research; A.M. prepared figures; A.M. and E.S. drafted manuscript; A.M. and S.M. edited and revised manuscript; A.M., E.S., and S.M. approved final version of manuscript.