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Initial information on the newly discovered hormone leptin suggests a primary role in energy balance and body weight maintenance. Recent published information suggests that leptin has an impact on several physiological systems, including neuroendocrine and immune function, as well as being involved in growth and development. Although the role of leptin in these areas is only partially understood at best, even less is known about the effect of exercise on plasma leptin concentrations. Further, if exercise has an impact on leptin concentration, how then does exercise affect overall leptin function? This article considers leptin function and the impact that exercise has on blood leptin concentrations, and suggests future directions for research on exercise and leptin.
Leptin, a hormone synthesized primarily by adipose tissue and secreted into the circulatory system, is a purported satiety factor with receptors in the hypothalamus. Human leptin is a relatively small protein (16 kDa) which shares a high degree of homology with other species such as mice (84%) and rats (83%). Although rare in humans, leptin mutations in mice result in leptin deficiency and lead to early onset obesity, hyperphagia, and hypothalamic hypogonadism. Unlike leptin deficient mice, humans deficient in leptin do not suffer from hyperinsulinaemia, hyperglycaemia, hypercorticism, or hypothermia. Although regulation of leptin synthesis and release is poorly understood, a distinct circadian pattern for plasma leptin concentrations has been observed and is similar to that of prolactin and thyroid stimulating hormone.1 Conflicting evidence implicates insulin as a stimulator for leptin release and/or synthesis; however, plasma leptin concentrations may change independently of plasma insulin change. To date, two interventions consistently lower plasma leptin concentrations: dietary energy restriction and a single exercise session. In contrast, tumour necrosis factor α, which is present during immune response to foreign bodies, stimulates leptin release into the circulation.
Although many different factors are involved in leptin regulation, recent evidence suggests that it is stored in vesicles within adipose tissue, and this may complicate any association between plasma leptin concentrations and leptin synthesis regulation. For example, β-3 receptor blockade in adipose tissue decreases leptin mRNA concentrations in adipose tissue when compared with non-blocked control groups, despite unaltered plasma leptin concentrations.2 Interestingly, plasma leptin concentrations are consistently associated with adiposity in a negative feed back loop (possibly to regulate food intake).
Leptin acts through a membrane bound receptor (Ob-R) identified in hypothalamic and haemopoietic cells. A homodimer, the Ob-R receptor is a member of the class I cytokine receptor family which includes interleukin-6. In the hypothalamus, leptin activated Ob-R receptors are thought to regulate eating behaviour, cortisol release, immune function, and other growth factors—for example, elevated leptin concentration signals adequate nutrition and permits growth and sexual development while maintaining eating behaviour. In haemopoietic cells, however, activated leptin receptors stimulate platelet aggregation possibly leading to accelerated vascular disease.3 Ob-R mutations are rare in humans, but lead to the same disorders as found in leptin deficient patients.
Studies examining the effects of a single exercise session and plasma leptin have found conflicting results. Dirlewanger et al4 found no changes in plasma leptin in response to moderate exercise performed during a three day period. Energy intake was kept isoenergetic at either 1.3 times basal metabolic rate or increased to meet the energy expenditure induced by the exercise. Perusse et al5 measured plasma leptin before, after 10–12 minutes of 50 W cycle ergometry, and immediately after reaching maximal exertion. No differences in plasma leptin were found when compared with the baseline value.
In contrast, Essig et al6 found a 30% reduction in leptin 48 hours after exercise that required about 6270 kJ (1500 kcal) of energy expenditure. Using the same subjects and experimental design, no differences were found at any time points after an exercise session requiring 3344 kJ (800 kcal) of energy expenditure. Tuominen et al7 also found a 34% decrease in serum leptin 44 hours after a two hour exercise period performed at 75% vo2max. Hilton and Loucks8 examined calorie restriction, exercise, and exercise with calorie restriction. Exercise with calorie restriction was the only treatment that produced a decrease in plasma leptin concentrations 24 hours after exercise. Thong et al9 found somewhat similar results by inducing weight loss through diet restriction only, exercise only, or exercise without weight loss. The diet only and exercise only protocols both resulted in significant reductions in body weight (7.5 kg) and in plasma leptin (about 5 ng/ml), yet the exercise without weight loss intervention produced no change in plasma leptin concentration.
Longitudinal exercise training studies have also reported conflicting results. Kraemer et al10 did not find any changes in leptin in obese women after a nine week aerobics class (estimated energy expended was 1256 kJ per session). Subjects maintained their normal diets throughout the study. Even though physical fitness improved, subject energy expenditure in conjunction with no reduction in energy intake may not have been enough of a stimulus to reduce plasma leptin. Conversely, Gutin et al11 found decreased plasma leptin in overweight children participating in a four month structured exercise and play programme.
Although existing published information is inconclusive, the results from studies evaluating a single exercise session indicate that leptin concentrations can be reduced in the days after exercise if the exercise session meets an energy expenditure threshold. Results from longitudinal exercise training studies are less clear. If plasma leptin concentrations are to be altered, an undefined threshold for total energy deficit as a result of either exercise training or reduced calorie intake probably exists.
Considering that obesity is a primary health concern and that many people who loose weight regain part if not all of that weight and that leptin in animal models is involved in regulating eating behaviour, understanding the impact of various lifestyle interventions such as exercise on plasma leptin concentrations and the regulation of leptin release and/or synthesis is an important public health concern. Future exercise research studies should focus on the following areas.
Are adverse health consequences associated with elevated plasma leptin concentrations? If so, are the adverse consequences a direct result of leptin concentrations or the result of adiposity or lifestyle behaviour?
What are the benefits of lowering plasma leptin concentrations through exercise and/or diet if they are involved in the negative feedback loop regulating eating behaviour?
Does a single exercise session alter plasma leptin concentrations directly or are altered plasma leptin concentrations a result of a change in the balance of energy intake and expenditure? Currently, the evidence suggests that the energy balance is more important. However, positive energy balance states have not been tested with or without exercise.
What is the mechanism(s) for exercise altered regulation of leptin synthesis and release?
What impact does both a single exercise session and habitual exercise participation have on leptin synthesis and/or release, and how does an altered plasma leptin concentration impact on leptin receptor density (Ob-R receptors in the hypothalamus)?
In conclusion, leptin is known to be involved in physical and sexual maturity; however, we do not know whether elevated leptin concentration is a symptom or underlying factor in obesity, nor do we understand how exercise regulates plasma leptin concentrations.
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