Peripheral signals of energy homeostasis as possible markers of training stress in athletes: a review


Journal Title (Medline/Pubmed accepted abbreviation): Metab Clin Exp
Year: 2011
Volume: 60
Number:3
Page numbers:335-350
doi (if applicable): 10.1016/j.metabol.2010.02.009

Summary of the article:
Athletes often implement intense training regimens that include high amounts of physical stress on the body. Some stress is “good”, in that it activates protein turnover and specific hormonal pathways such as growth hormone (GH). However, it is possible for athletes to overtrain, causing the rate of protein breakdown to exceed that of protein synthesis. Signals reporting status of energy stores and muscular stress from exercise are received and integrated in the hypothalamus, which in turn sends its own signals to regulate other hormonal pathways. The measurement of hormones such as GH and insulin-like growth factor (IGF-1), which are controlled by the hypothalamus, have been employed to measure training status (not intense enough → too intense). It has been proposed that the input signals to the hypothalamus (for example peptide hormones that report energy availability, cytokines to report on stress, or other peripheral signals) may be able to be measured directly to report on the physical status of an athlete. It is thought that these metrics may be able to more accurately represent an athlete’s physical stress condition from day to day, whereas GH and IGF-1 fluctuate significantly throughout the day. Used together, both sets of measures may more accurately inform the athlete of his or her physical condition as well as the effects (either positive or negative) that training is providing.

Leptin. Leptin is a protein that is secreted by adipose tissue and the amount of lipid stored influences leptin secretion. When energy intake is restricted, leptin levels decrease and, via signal integration by the hypothalamus, neuropeptide-Y levels increase, thereby increasing appetite. Exercise has been shown to reduce leptin levels in athletes, perhaps due to the increased energy demands and/or reduced amount of energy availability. Observations made with intensely training rowers suggest that leptin levels may fall more rapidly during exercise when the body is overtrained, thus making leptin a potential reporter hormone to identify overtraining in an athlete.

Adiponectin. Adiponectin is a hormone that regulates glucose and lipid metabolism. Circulating adiponectin levels are inversely associated with body fat stores; the less fat (energy) available, the higher the adiponectin levels. In general, acute exercise increases adiponectin levels after exercise. It has been shown that adiponectin responses to exercise are influenced by athleticism; higher-performing rowers showed higher exercise-induced adiponectin levels. This response is believed to imply that these athletes were in a healthier, fully-recovered physical condition. Athletes who were believed to not be fully recovered displayed lower exercise-induced adiponectin levels.

Ghrelin.Ghrelin is secreted by cells in the gastrointestinal tract also in response to low energy availability. The hypothalamus responds by eliciting a feeling of hunger. However, most studies have shown that exercise, resulting in negative energy balance, does not increase total ghrelin levels. However, a few studies that implemented intense training procedures were able to show an increase in ghrelin levels. One possible explanation of these phenomena is that exercise induces a reduction in appetite immediately after exercise, and ghrelin levels could coincide with this response. In general, ghrelin levels do not appear to be sensitive enough to accurately report energy availability or recovery status in athletes.

Inflammatory cytokines. Exercise initiates an inflammatory response that is communicated to other cells via proteins called cytokines. Controlled amounts of inflammatory response can promote cellular repair and protein synthesis, but overtraining can cause a prolonged increase in inflammatory cytokines that can lead to systemic and/or chronic inflammation. Cytokines involved in the response to exercise include interleukin-6 (IL-6) and tumor necrosis factor α (TNF-α), which are produced within the muscle tissue and act locally, and interleukin 1β (IL-1β), which is thought to be released systematically in response to more intense exercise. It has been demonstrated that carbohydrate availability has a direct impact on cytokine release; carbohydrate ingestion is believed to attenuate the cytokine response to exercise and, moreover, higher glycogen stores appear to attenuate increases in IL-6 after exercise. There is not enough data to confirm that carbohydrates per se are imperative to cytokine attenuation, it may be simply a positive energy balance that regulates their release. Chronically elevated levels of inflammatory cytokines or increased sensitivity to exercise-induced cytokines may explain “underperformance syndrome” in some athletes. Because overtraining and/or lack of adequate recovery can lead to elevated levels of cytokines, inflammatory cytokines may provide a good metric for determination of overtraining.

Interaction between metabolic hormones. Leptin, adiponectin, and many other metabolic hormones have receptors in the hypothalamus. The hypothalamus receives and integrates all of the signals from the body, sometimes opposing, and generates an appropriate response. It is thought that many hormonal responses are linked, including adiponectin with insulin and/or inflammatory cytokines and that exercise may change the dynamic interactions between these hormones. Unfortunately, this research is still in its infancy and additional research is warranted before these associations are elucidated.


Interpretation of findings/Key practice applications:

Athletes, because of their higher energy demands and increased physical stress, are in a different hormonal balance than sedentary individuals. Fluctuations in some of these hormones, such as leptin, adiponectin, and some of the inflammatory cytokines, are sometimes able to be predicted. Therefore, when these hormonal patterns are out of balance, athletes, their coaches, or their trainers may be able to identify overtraining or overreaching and alter the athlete’s training plan accordingly. Due to the lack of understanding of these hormonal processes and their implications for training at this time, it would not yet be appropriate to implement these practices in training. However, this type of assessment has potential in the future.

Limitations:

Due to ethical concerns regarding designing studies with exercise protocols severe enough to promote overtraining, athletes that have been studied were not necessarily “overtrained”, making it hard to identify markers of overtraining. Most athletes in the reviewed studies were training very intensely as part of the study protocol, but were elite athletes whose bodies were accustomed to the intensity. There are many, many hormones, some, undoubtedly, that we have not even discovered yet, that respond to exercise. The hypothalamus already receives and integrates all of these signals and, at this point, it may be easier to rely on the signals generated from the hypothalamus or pituitary (such as levels of GH) to assess overall body status, rather than trying to reach our own conclusions from only a few of the hypothalamic inputs. Blood samples may not be a practical way for athletes to assess overtraining on a regular basis. There may be noninvasive measures (measurement of saliva samples, jump height, running speed, or activities specific to the athletes’ training) that could determine physical condition.
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