Molecular Pathways Mediating Immunosuppression in Response to Prolonged Intensive Physical Training, Low-Energy Availability, and Intensive Weight Loss

Abstract

Exercise and exercise-induced weight loss have a beneficial effect on overall health, including positive effects on molecular pathways associated with immune function, especially in overweight individuals. The main aim of our study was to assess how energy deprivation (i.e., “semi-starvation”) leading to substantial fat mass loss affects the immune system and immunosuppression in previously normal weight individuals. Thus, to address this hypothesis, we applied a high-throughput systems biology approach to better characterize potential key pathways associated with immune system modulation during intensive weight loss and subsequent weight regain. We examined 42 healthy female physique athletes (age 27.5 ± 4.0 years, body mass index 23.4 ± 1.7 kg/m 2 ) volunteered into either a diet group ( n = 25) or a control group ( n = 17). For the diet group, the energy intake was reduced and exercise levels were increased to induce loss of fat mass that was subsequently regained during a recovery period. The control group was instructed to maintain their typical lifestyle, exercise levels, and energy intake at a constant level. For quantification of systems biology markers, fasting blood samples were drawn at three time points: baseline ( PRE ), at the end of the weight loss period ( MID 21.1 ± 3.1 weeks after PRE ), and at the end of the weight regain period ( POST 18.4 ± 2.9 weeks after MID ). In contrast to the control group, the diet group showed significant (false discovery rate <0.05) alteration of all measured immune function parameters—white blood cells (WBCs), immunoglobulin G glycome, leukocyte transcriptome, and cytokine profile. Integrative omics suggested effects on multiple levels of immune system as dysregulated hematopoiesis, suppressed immune cell proliferation, attenuated systemic inflammation, and loss of immune cell function by reduced antibody and chemokine secretion was implied after intense weight loss. During the weight regain period, the majority of the measured immune system parameters returned back to the baseline. In summary, this study elucidated a number of molecular pathways presumably explaining immunosuppression in individuals going through prolonged periods of intense training with low-energy availability. Our findings also reinforce the perception that the way in which weight loss is achieved (i.e., dietary restriction, exercise, or both) has a distinct effect on how the immune system is modulated.

Physical health and symptoms of relative energy deficiency in female fitness athletes

“…The most successful athletes were more experienced in competitions, consumed more carbohydrates and total energy, and were leaner at competition time, compared to the less successful ones. Low total fat mass is associated with low energy availability and high risk of several symptoms of RED‐s, and the tendency of a clinically reduced RMR with the more successful FA in the current sample may indicate such a scenario. The findings from this subgroup analysis may highlight important practice for success in this sport, but do also bring up concern for health among the most successful athletes.…”

Reasons for and Consequences of Low Energy Availability in Female and Male Athletes: Social Environment, Adaptations, and Prevention

“…Supporting of the RED-S definition, which includes impairments of immunity, is the association between LEA and upper respiratory tract infection (URTI) risk in female athletes [110]. In addition, Sarin et al described immunosuppression after energy restriction in immune cells such as T cells and B cells [111]. Furthermore, interleukin-6 (IL-6) expression mediating inflammation is reduced by sufficient energy intake before exercise in order to spare muscular glycogen [112].…”

“…Similarly, haematological constraints, such as abnormal bruising, anaemia, low haemoglobin, iron, or ferritin, are 1.6 times more likely in female athletes at risk for LEA [115]. A dysfunctional haematopoiesis may be present in female athletes with LEA, since prolonged energy restriction and intense exercise are associated with lower erythrocyte and platelet counts, while the number of white blood cells increases [111].…”

Mitochondrial bioenergetic pathways in blood leukocyte transcriptome decrease after intensive weight loss but are rescued following weight regain in female physique athletes

“…| DISCUSSIONThe current integrated high-throughput omics study, utilizing a unique group of female physique athletes who voluntarily performed high volumes of exercise together with a prolonged period of low energy availability,10,12,13 represents an…”