Leptin and exercise: new directions

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 eVect of exercise on plasma leptin concentrations. Further, if exercise has an impact on leptin concentration, how then does exercise aVect 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 suVer 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. 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 á, which is present during immune response to foreign bodies, stimulates leptin release into the circulation. Although many diVerent 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, â-3 receptor blockade in adipose tissue decreases leptin mRNA concentrations in adipose tissue when compared with nonblocked control groups, despite unaltered plasma leptin concentrations. 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. Ob-R mutations are rare in humans, but lead to the same disorders as found in leptin deficient patients. Studies examining the eVects of a single exercise session and plasma leptin have found conflicting results. Dirlewanger et al 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 al measured plasma leptin before, after 10–12 minutes of 50 W cycle ergometry, and immediately after reaching maximal exertion. No diVerences in plasma leptin were found when compared with the baseline value. In contrast, Essig et al 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 diVerences were found at any time points after an exercise session requiring 3344 kJ (800 kcal) of energy expenditure. Tuominen et al also found a 34% decrease in serum leptin 44 hours after a two hour exercise period performed at 75% V~O2MAX. Hilton and Loucks 8