The factors involved in the processes of lipolysis, transport and oxidation of fatty acids are analyzed, paying special attention to those that limit the oxidation of fats: hormonal, nervous and circulatory factors, and the effects of exercise on them. Lipolysis of adipose tissue is heterogeneous, since the largest amount of fatty acids used during aerobic exercise derives from subcutaneous abdominal adipose tissue. Understanding these steps is important to clarify what type of exercises, how much and how they should be applied for the oxidation of fatty acids.
Key Words: lipolysis, catecholamine, insulin, oxidation.
INTRODUCTION
Fatty acids represent a very large source of energy reserves throughout the body. The oxidation of fatty acids during aerobic exercises allows you to prolong physical activities and delay the onset of glycogen depletion. However, although the fat stores are relatively large, the ability to oxidize fatty acids is limited, making carbohydrates the dominant substrate. The reason for limiting the use of fat stores may be due to the little information available about the role of fat during exercise, which affects the understanding of fat metabolism during physical activity. For this reason, the development of exercises must be supported by a solid conceptual framework,
This work proposes to incorporate fundamental contributions from Biology research to rule out the use of empirical practices without scientific support.
The methodology chosen was the bibliographic search in scientific journals, which allowed reaching conclusions of interest. The analysis was divided into three parts:
- Mobilization of fatty acids (FA) from adipose tissue.
- Transport of AG to the muscle.
- AG consumption by the muscle cell.
The first part deals with the stimulating and inhibitory factors of lipolysis and their relationship with exercise. The second part is dedicated to knowing how the transport of AG to the muscle is carried out and how it varies according to the intensities of the exercise. The third part addresses the factors involved in the consumption of fatty acids by the muscle cell. These factors must be enhanced with aerobic resistance training.
Also considered: Other aspects to take into account in lipid metabolism and exercise, such as: age, sex and hormones.
The main objective of this review is to provide Physical Education and Sports professionals with an overview of the knowledge of fat metabolism during exercise, paying special attention to the factors that limit fat oxidation and the effects of the exercise on them.
“From there, the openness to criticism and debate is totally welcome since only from it, the less probable can become a little more probable and the erroneous, which always exists in this type of knowledge, in a little less wrong ”(Di Santo Mario, 1997).
METHODOLOGY
Were analyzed:
- Mobilization of fatty acids (FA) from adipose tissue.
- Transport of AG to the muscle.
- AG consumption by the muscle cell.
- Mobilization of GA from adipose tissue
1.1. Stimulating factors of lipolysis
A- Catecholamines
They are activators of beta adrenergic receptors. According to Horowitz JF (2003), the regulation of lipolysis can vary depending on the adrenergic receptors located in different anatomical sites of the adipose tissue layer or stratum. The variability in the lipolytic rate in different layers of adipose tissue is related to regional differences in the density and function of beta adrenergic receptors (Horwitz, 2001):
- Fat cells from intra-abdominal adipose tissue (Visceral adipose tissue TAV).
- Subcutaneous fat of the abdomen (TASA).
- Subcutaneous gluteal and hamstring fat.
Intra-abdominal adipose tissue is the most lipolytically active deposit, and fat accumulation in this region is associated with a wide range of clinical complications (Pasman et al, 2002). The FA released from this adipose tissue are taken up by the liver and cause an increase in VLDL (Horwitz, 2001). Despite this increase in lipolytic activity, intra-abdominal fat does not contribute significantly to muscle energy production.
Most of the FA released into the systemic circulation are derived from subcutaneous adipose tissue (SAD), particularly from abdominal subcutaneous adipose tissue because they are more sensitive to beta agonist receptors than gluteal and femoral subcutaneous adipose tissue.
TGIMs (intramuscular triglycerides) are lipid “droplets” deposited within muscle cells. A large body of evidence suggests that TGIMs provide, at most, between 10 and 55% of total fat oxidation during exercise (Horowitz, 2003). We can also say that it is a quite controversial point in the bibliography, since:
- Horowitz & Klein (2000) found that total fat oxidation during moderate intensity endurance exercises was higher in abdominally obese than in lean women, due to increased oxidation of non-plasma AGs presumably derived from TGIM.
- Steffensen et al (2002) revealed that, despite the degree of training, women at rest had a higher TGIM content than men; Furthermore, regardless of training status, women used higher amounts of TGIM than men during prolonged exercise.
Another potential source of fuel for exercise is circulating triglycerides (TG), which are hydrolyzed by lipoprotein lipase (LPL), located in the capillary endothelium of skeletal muscles.
- Heterogeneous lipolytic activity in different layers of adipose tissue
Figure 1. Source: Modified graph from Horwitz, JF (2003)
Catecholamines activate the lipolytic cascade, by binding to different types of beta adrenoceptors located on the plasma membrane of adiposites. The role of the three different adiposite receptors in lipolytic regulation is not well understood. The affinity for catecholamines differs between the three adrenoceptors (Horowitz, 2001):
- Beta 2> beta1> beta 3 for epinephrine
- Beta 1> or = beta 2> beta 3 for norepinephrine
However, each Beta receptor differs in resistance to desensitization:
- Beta 3> beta 2> or = beta 1
This Beta 3 adrenoreceptor is mainly active in omental (visceral) adipose cells and is also present in mammary and subcutaneous fat in vivo.
In this regard, the heterogeneous distribution of the different types of beta receptors in various layers of adipose tissue seems to reflect an important role of these in the regional regulation of lipolysis.
A very important enzyme that is involved in the regulation of lipolysis in adipose tissue is the hormone sensitive lipase (HLS), a rate-limiting enzyme for the release of fatty acids from adipose tissue triglycerides into the circulation.
- Blood flow in adipose tissue (FSTA)
The increase in FSTA is coordinated with the increase in epinephrine produced by low to medium intensity endurance exercises (25 to 65% of VO2 max), which improves AG lipolysis. It was also discovered that there is a lack of coordination between FSTA and lipolytic activity when epinephrine concentrations are equal to or greater than 1.6nM. These concentrations cause a decrease in FSTA; however, the Ta of AGL and the Ta of Glycerol continue to increase (Horowitz et al, 1999).
However, it is interesting to note that the FFA Ta and the plasma FFA concentration increased abruptly when the exercise ended to 85% and, to a lesser extent, to 65% of VO2 max. This seems to indicate that the influx of FFA into plasma, after the end of the exercise, is not associated with increased lipolysis, which may reflect the entry into plasma of FFA “trapped” in adipose tissue during exercise, possibly due to to an inadequate blood flow in adipose tissue (Mora-Rodriguez and Coyle, 2000).
The decrease in FSTA during high intensity exercise produces a decrease in the transport of FFA within the circulation.
- Hormone sensitive lipase (LHS)
LHS is a rate limiting enzyme for the release of AG from adipose tissue TG into the bloodstream. Catecholamines and insulin are the hormones that regulate lipolysis in humans.
In the postprandial state, despite the great response to insulin after the meal, the normal suppression in the flow of AG is lower in obese abdominals compared to lean or obese people in the lower extremities of the body (Berger & Barnard, 1999) (Kim, Yeon et al, 2000). However, LHS is dependent on the size of the fat cell (Berger & Barnard, 1999). For this reason, a great mobilization of basal and postprandial GA enters into circulation in people with abdominal obesity, which seems to be a direct consequence of their excessive subcutaneous abdominal fat mass. This type of people who have great abdominal obesity also have a high basal lipolytic rate, and present a sharp increase in lipolysis during exercise, when compared to lean people,
1.2. Lipolysis inhibitory factors
Insulin
It is a catecholamine antagonist and an activator of alpha 2 adrenergic receptors that inhibit LHS activity and activate LPL.
The antilipolytic effects of insulin are greatest in fat cells of lower body subcutaneous adipose tissue, which appear to have a higher density of alpha 2 adrenergic receptors and fewer beta adrenergic receptors.
Although prolonged exercises cause an increase in plasma HG catecholamines, they also produce a concomitant reduction in insulin, which favors the release of AG. But the ingestion of carbohydrates before or during exercise, attenuates this response, raising glucose-insulin and significantly attenuating the catecholamine response to prolonged exercise. Furthermore, this ingestion increases the rate of carbohydrate oxidation (Horowitz et al, 1997).
Lactate
During low intensity exercises, lipids are the main source of energy. With increasing exercise intensity, the proportion of energy derived from lipid oxidation decreases. The factors responsible for this reduction in the mobilization of AGL are:
- Low availability of albumin in plasma to transport FFA.
- Low blood flow in adipose tissue.
Both favor restyrification over mobilization.
- High plasma lactate, which is a – presumed – adipose tissue mobilization inhibitor.
This last inhibitory factor has been put into doubt by an investigation by Trudeau et al (1999), who rejected the hypothesis that lactate could exert a direct inhibitory effect on lipolysis. The study was carried out with eight male subjects of average age 26, in good physical condition (59.87ml / kg / min. VO2 max). The result of the study suggests:
- Lactate applied locally to adipose cells in subcutaneous abdominal adipose tissue does not produce a decrease in the mobilization of fat from these deposits during exercise.
- However, given the specificity of this adipose tissue, this statement cannot be conclusive, since lactate can induce inhibition of lipolysis in other regions of fatty deposits. The suggested mechanisms by which lactate can inhibit lipolysis is the decrease in cAMP in adiposites; decreased adrenoceptor binding (Trudeau et al 1999).
Lipopreteinlipase (LPL)
LPL is a key regulator of fat accumulation in various fat areas. It was shown in men with a wide variation in body fat that triglycerides are taken up to a greater extent by TAV than by TASA. This suggests that other factors – such as LPL- may be important to regulate the uptake of TG in adipose tissue, such as Acylation Stimulating Protein (ASP), a strong stimulator of AGL restirification and TG synthesis in human adipose tissue. (Waychember, 2000).
The omental adipose tissue has, only in women, small adipose cells and less LPL activity than subcutaneous fatty adipose cells. Compared with men, lipid accumulation is higher in the femoral region of premenopausal women. In men, both LPL activity and LPL protein mRNA levels were higher in the abdomen than in gluteal fat cells; the opposite was observed in women (Wajchenberg, 2000).
1.3. Mobilization of AG from adipose tissue during endurance exercises
Durante ejercicios de baja intensidad, 25% del VO2 máximo, la lipólisis del tejido adiposo (medida como la tasa de aparición de glicerol en la circulación – Ta glicerol -) aumenta de 2 a 5 veces con respecto a los niveles de reposo (Mora-Rodriguez y Coyle, 2000). Durante el mismo tiempo, la tasa de reesterificación decrece, la que produce una mayor cantidad de AG liberados para ser oxidados en el músculo esquelético. Durante ejercicios prolongados de baja intensidad, la tasa lipolítica aumenta considerablemente después de 4 horas (10 veces mayor que en los niveles de reposo) (Horowitz, 2001).
Although the lipolytic rate remains relatively high with increasing exercise intensity, the release of GA into the circulation declines. The mechanisms responsible for this reduction in the mobilization of GA are unknown; however, because the concentrations increase dramatically immediately after intense exercise, it is believed that the reduction in the release of GA into the circulation may be the result of a restriction of blood flow in adipose tissue, caused by a blood vessel constriction caused by catecholamines (Mora-Rodriguez & Coyle, 2000).
- Transport of AG to the muscle
The transport of fatty acids to the muscle is carried out by means of albumin and the blood flow in adipose and muscle tissue.
The low availability of albumin in the blood, plus a reduced blood flow, favors the reesterification of AGL.
In a study carried out by Mora-Rodriguez and Coyle (2000), it was observed that the occurrence rate (AD) of AGL increased abruptly when the exercise ended, performed at 85% of VO2 maximum; to a lesser degree, when doing it at 65% of VO2 maximum; and it was low after doing it at 25% VO2 max. This appears to demonstrate the entry into plasma of FA “trapped” in adipose tissue during exercise. But, despite a higher lipolytic rate, the transport and oxidation of AG by the muscle is reduced, due to a reduction in FSTA.
- AG consumption by the muscle cell
The consumption of fatty acids by the muscle cell is limited by what we will call mitochondrial factors. Since fat oxidation occurs in the mitochondria, the higher mitochondrial density, characteristic of resistance training, produces an increase in fat oxidation and a reduction in glycolytic flux, both of muscle glycogen and of blood glucose.
During low intensity exercise, resistance-trained subjects have a higher balance between Td FFA and total fat oxidation than do untrained subjects, since the availability of FA does not limit fat oxidation. It is likely, then, that oxidation is limited by mitochondrial factors. Furthermore, the enzyme that regulates the entry of AG into the mitochondria – Carnitin Palmito transferase I, is considered a rate-limiting step in AG oxidation (Mora-Rodriguez and Coyle, 2000).
In people with abdominal obesity, a low availability of this enzyme has been found in the skeletal muscles, as well as a reduced activity of some key enzymes of mitochondrial oxidation (Howoritz, 2001).
According to Horowitz (2001), the entry of fatty acids into the muscle is much more complex, and involves a series of transporter proteins: protein-bound plasma membrane FA, translocase fatty acid (FAT / CD36) and FA transporter proteins .
Other considerations
Other aspects to take into account are: age and sex, differences between the sexes, hormones and their receptors in adipose tissue and fasting.
Age and Sex
The amount of visceral fat increases with age in both sexes, and this increase is present, both in subjects with normal weight (body mass index -BMI- 18.5 to 24.9 kg / m2), overweight (BMI 25 to 29.9) and in obese subjects (BMI greater than 30 kg / m2); furthermore, it is higher in men than in women (Wajchemberg, 2000).
It was found that in young, obese or lean women, the subcutaneous abdominal fat area was predominant over the visceral abdominal fat, which were measured by computed tomography (Wajchemberg, 2000). This fatty topography was observed in young and middle-aged women; while over 60 years of age, a shift towards an android-type fat distribution was observed. This fat redistribution is due to a relative and absolute increase in visceral fat deposits, particularly in obese women, which appears to be with an increase in androgenic activity in postmeospausal women.
In men, a close linear correlation between age and visceral fat volume was demonstrated, suggesting that visceral fat continually increases with age. This correlation was present in women but with a slight inclination in the premenopausal condition.
The accumulation of fat in visceral adipose tissue explains the difference in cardiovascular risk according to gender.
Differences between sexes
Differences in visceral fat mobilization were investigated in obese men and women, with the same BMI and age, who underwent elective surgeries (Wajchenberg, 2000). It was observed that the men had a large number of fat cells, but there were no lipolytic differences in specific beta 1 and beta 2 adrenoceptors, or in the antilipolytic effect of insulin. However, the lipolytic sensitivity of beta 3 adrenoceptor was 12 times higher in men than in women, and the sensitivity of alpha 2 adrenoceptor antilipolytic was 17 times lower in men than in women.
These results were conclusive regarding the role of catecholamines on the mobilization of FFA from visceral fat to the portal venous system, being greater in men than in women. This factor may contribute to the specific differences between the sexes, observed in metabolic disorders accompanied by obesity.
Friendlander et al (1998) suggest that training may produce better subcutaneous abdominal lipid mobilization in women than in men due to:
- Upregulation of beta adrenergic stimulation.
- Low alpha 2 adrenergic inhibitory regulation.
- Mobilization and oxidation of AG enhanced by an interaction of growth hormone and estrogens.
This study contrasts with the research presented by Romjin et al (2000), whose results indicated that metabolic substrates in endurance-trained women respond similarly to those of men.
In the study by Mittendorfer et al (2002), the effect of sex on lipid metabolism during moderate intensity endurance exercises was examined. Men and women with equal adiposity and aerobic condition were evaluated to rule out influences attributed to sex and its relationship with metabolic substrates. The researchers found that:
- The whole body lipolytic rate and the availability of plasma FFA were higher in women than in men.
- The whole-body oxidation rate of AG was similar in men and women.
- The source of FA used as fuel differs between sexes: compared to men, women oxidized greater plasma FFA derived from adipose tissue TG and less amount of FA derived from TGIM.
Leptin
It is a hormone produced by adiposity that regulates food intake and energy expenditure at the hypothalamus level. Apparently, the physiological role of leptin -when it rises due to an increase in adiposity- is to generate a signal that limits weight gain (Leptin, from the Greek, whose root slow means thin). The leptin-producing gene OB is secreted by adiposites and acts as a feedback signal with the CNS, particularly with the satiety center of the hypothalamus. OB gene expression and leptin levels in obese humans reflect total adiposity, suggesting that leptin is probably associated with endogenous insensitivity to it in obese humans.
The most important factors in the regulation of OB gene expression and leptin secretion are (Pasman et al, 1998; Thong et al, 2000):
- Training exercises: not only influence obesity, but also insulin resistance and body composition.
- Insulin (insulin resistance).
- Fat mass.
- Sex hormones.
Chronic changes in the energy balance, whether due to diet or exercise, can modulate the expression of the OB gene and, therefore, the secretion of leptin (Thong et al, 2000); the expression of the OB gene is higher in subcutaneous adipose tissue than in visceral adipose cells. A significant correlation between changes in insulin and in leptin was found in numerous studies, suggesting that variations in leptin levels may occur through insulin-dependent regulatory mechanisms (Pasman et al, 1998). Insulin sensitivity improved after exercise or caloric restriction-induced weight loss (Thong et al, 2000).
Hormones and their receptors in adipose tissue
There are several hormones that increase in plasma during prolonged exercise:
- HC levels increase.
- Insulin levels drop.
- Glucagon levels increase.
- Cortisol significantly increases depending on the duration of the exercises.
Hyperglycemia attenuates hormonal responses by activating alpha receptors located in the ventromedial-ventrolateral nuclei of the hypothalamus ((Horowitz, 2000).
Hormone receptors in adipose tissue (Wajchenberg, 2000)
- Glucocorticoid receptors: they have a high density in visceral adipose tissue (greater number of receptors in visceral adipose tissue than in subcutaneous adipose tissue).
- Androgen and estrogen receptors: adiposites have specific receptors for androgens with a higher density in visceral fat cells than in subcutaneous adipose tissue. In men, testosterone induces an increase in lipid mobilization, apparently being higher in visceral fat due to the high density of androgen receptors. In women, however, there is an association between visceral fat accumulation and hyperandrogenity, despite the documented effects of testosterone on lipid mobilization and the expected decrease in visceral fat. However, treatment with low estrogens regulates the density of these receptors, thereby protecting adipose tissue from androgenic effects.
- Growth hormone receptors: this hormone is clearly related to the regulation of visceral mass in humans.
- Thyroid hormone receptors: they have multiple catabolic effects on fat cells (interaction with the adrenergic system).
- Adenosine receptors: behaves as a potent antilipolytic and vasodilator agent; It can be considered as an autoccrine regulator of lipolysis and insulin sensitivity in adipose tissue.
Fasting
During fasting exercise, lipolysis exceeds fat oxidation primarily due to low insulin concentration. Lipolysis exceeds fat oxidation by 15-25%, at rest or during exercise when the subject is fasting (Horowitz, 2001).
Horowitz & Klein (2000) directly determined that lipolysis is markedly lower during a carbohydrate-rich meal. They also observed a 38% reduction in performance during fasting, when exerted at 70-86%, which could not be reversed by carbohydrate ingestion during exercise (Horowitz et al, 1997).
CONCLUSION
Fats are the main source of energy during exercise. Hormonal, nervous and circulatory factors are involved in the release of fatty acids from adipose tissue for oxidation in the muscle cell. The lipolysis of adipose tissue is heterogeneous, since the greatest amount of fatty acids used during aerobic exercise is derived from the subcutaneous abdominal adipose tissue. There is research that tries to explain the factors involved in the release, transport and consumption of fatty acids in the working muscle (Berger & Barnard, 1999; Horowitz et al, 1999; Horwitz, 2001; Horowitz, 2003; Mora-Rodriguez & Coyle , 2000).
Understanding these steps, which involve a number of factors, is important to clarify what type of exercises, how much, and how they should be applied for the oxidation of fatty acids.
Practical applications
Next, a series of exercises supported by a solid conceptual framework will be presented, which includes the contributions of research in the area of Biology cited in the preceding paragraphs.
- Walks During low intensity exercises, 25% of VO2 maximum, lipolysis of adipose tissue (measured as the rate of appearance of glycerol in the circulation – Ta glycerol) increases 2 to 5 times with respect to resting levels (Mora-Rodriguez & Coyle, 2000).
- Walking, low intensity fasting running. During fasting exercise, which is accompanied by low insulin levels, total lipolysis exceeds fat oxidation.
- Long-duration, low-intensity runs. The rate of reesterification decreases, which produces a greater amount of FA released to be oxidized in skeletal muscle; the lipolytic rate increases considerably, the blood flow in adipose and muscle tissue is increased, the sensitivity of adipose tissue to epinephrine improves (Horowitz, 1999).
- Alternate low intensity, short duration runs with long duration, low intensity runs. It was observed that FFA Ta and plasma FA concentration increased abruptly when the exercise ended at an intensity of 85% VO2 max.
