JPFSM: Short Review Article
The effects of exercise on adipokines
-Focus on circulating adiponectin level in human studies-
Department of Health and Sports Sciences, Kyoto Pharmaceutical University, 5 Nakauchi-cho, Misasagi, Yamashina-ku, Kyoto 607-8414, Japan
Waseda Institute for Sport Sciences, 2-579-15 Mikajima, Tokorozawa, Saitama 359-1192, Japan Received: June 12, 2012 / Accepted: August 3, 2012
Abstract
Adipose tissue is an important site for energy storage and energy homeostasis. Inaddition, it has been recognized as an endocrine organ that produces and secretes a number of bioactive peptides or proteins called “adipokines”. These molecules are directly and indirectly involved in the pathogenesis of metabolic disorders, such as obesity, type 2 diabetes, cardiovas- cular diseases, and metabolic syndrome. Until now, a number of adipokines (e.g. adiponectin, leptin, tumor necrosis factor-α interleukin-6, and retinol-binding protein-4) have been identified and their functions have been elucidated. Among these, adiponectin is known to be involved in improvement in insulin sensitivity and endothelial function, and promotion of fat oxidation.
Aerobic exercise also has the same effects. The benefits of aerobic exercise could be induced through changes in adiponectin levels. In this short-review, focus is given to the effects of aero- bic exercise on circulating adiponectin levels in humans.
Keywords : adiponectin, adiponectin oligomers, aerobic exercise
Structure and function of adiponectin
Adiponectin was first identified in 1995, and is also referred to as Acrp30
1), AdipoQ
2), apM1
3)or GBP28
4). Adiponectin comprises of 244 amino acids, and is mainly composed of a carboxyl-terminal globular domain and an amino-terminal collagen domain
5). Adiponectin exists in blood as a proteolytic cleavage fragment of the globular C-terminal domain (globular adiponectin) as well as a full-length form (full-length adiponectin). Globular adi- ponectin mainly exists as a trimer, whereas full-length adiponectin occurs as a low-molecular weight (LMW) trimer, a middle-molecular weight (MMW) hexamer, and high-molecular weight (HMW) 12- to 18-mer adiponec- tin
6,7). In particular, HMW adiponectin is believed to be the most biologically active form of the 3 oligomers
7). AdipoR1 and AdipoR2 receptors have been identified as adiponectin receptors; AdipoR1 is highly expressed in skeletal muscle, whereas adipoR2 is expressed in the liver
8).
Adiponectin levels are low in obese humans
9), and lower adiponectin levels are associated with a higher in- cidence of diabetes
10). Furthermore, adiponectin levels are inversely correlated with insulin resistance
9). Hypoadi- ponectinemia is independently associated with metabolic syndrome
11); it is also reportedly associated with cardio- vascular disease
12)and hypertention
13). HMW adiponectin
levels and the ratio of HMW to total adiponectin levels are associated with metabolic syndrome
14), insulin resis- tance
15)and cardiovascular diseases
16)to a greater extent than total adiponectin levels.
Adiponectin has direct and indirect functions that are primarily related to the promotion of insulin sensitivity and endothelial function, and the inhibition of inflamma- tory mediators. It also inhibits hepatic glucose produc- tion
17,18)and stimulates glucose uptake and fat oxidation in skeletal muscle and other tissues
18). Furthermore, it directly increases nitric oxide
19), reduces the expression of adhesion molecules in endothelial cells
20), and elicits anti- inflammatory properties by decreasing cytokine produc- tion
21).
The effects of aerobic exercise on circulating total adi- ponectin and adiponectin oligomer levels
As mentioned above, adiponectin improves insulin sen- sitivity and endothelial function, and stimulates fat oxida- tion. Aerobic exercise increases insulin sensitivity
22), en- hances vascular endothelial function
23), and accelerates fat oxidation
24). It is hypothesized that the benefits of aerobic exercise are induced through changes in adiponectin lev- els.
1. The effects of acute aerobic exercise
It seems quite probable that the change in circulating total adiponectin levels is minor in response to acute Correspondence: [email protected]
Shigeharu Numao
aerobic exercise. Strenuous intermittent exercise at 60%
(10 min), 75% (10 min), 90% (5 min), and 100% maximal oxygen consumption (V
・o
2max) (5 min) did not change total adiponectin levels
25). A two-hour cycling exercise at 50% V
・o
2max under normal, fasting conditions, and after the pharmacological inhibition of adipose tissue lipolysis, also did not change total adiponectin levels during and af- ter the exercise
26). Moreover, Højbjerre et al.
27)investigated the change in circulating total adiponectin levels during and after 60-min acute aerobic exercise at 55%V
・o
2max in lean and obese males. Despite the increase and decrease in interstitial adiponectin levels and adiponectin mRNA in subcutaneous abdominal adipose tissue respectively, circulating total adiponectin levels did not change during and after the exercise. In contrast, Jurimae et al.
28)reported that circulating total adiponectin levels decreased slightly immediately after rowing exercise; however, the levels re- turned to baseline at 30 min after the exercise. To our best knowledge, however, no study has reported an increase in circulating total adiponectin levels in response to acute aerobic exercise.
HMW adiponectin represents the most biologically ac- tive form of the 3 adiponectin oligomers
7). Therefore, we investigated the continuous change in total and HMW adi- ponectin levels during moderate-exercise (50% V
・o
2peak, 60 min) and after the exercise (30 min) in healthy young males. HMW and total adiponectin levels during and after the exercise were not significantly different from those during a 90-min rest period
29). In addition, we recently reported the effects of exercise intensity on adiponectin oligomer levels in abdominally obese men
30). Nine un- trained abdominally obese men performed 60-min mod- erate-intensity (50%V
・o
2max) and high-intensity aerobic exercise (70%V
・o
2peak). Unexpectedly, total adiponectin levels decreased only during the high-intensity aerobic exercise. Furthermore, HMW adiponectin levels remained unchanged in both trials, whereas MMW + LMW adi- ponectin levels decreased, and the ratio of HMW to total adiponectin levels increased during the high-intensity aer- obic exercise (Fig. 1). The decrease in total and MMW+
LMW adiponectin levels correlated with a change in epi- nephrine levels. These findings suggest that high-intensity acute aerobic exercise modulates adiponectin by changing adiponectin oligomer levels; and a change in epinephrine levels during exercise is associated with alterations in circulating adiponectin levels. In addition, a reduction in MMW and/or LMW adiponectin levels may lead to reduced competition between adiponectin oligomers for binding to the adiponectin receptor; and fluctuations in the levels of MMW and/or LMW adiponectin levels in- directly reinforce the function of HMW adiponectin
31). However, since data on the effects of acute exercise on adiponectin oligomer levels is limited, further studies are needed.
2. Chronic aerobic exercise training
Data on the effects of chronic aerobic exercise training on circulating total adiponectin is inconsistent. Circulat- ing total adiponectin levels did not change in the popula- tion with type2 diabetes
32)and obesity
33)during a 12-week aerobic exercise intervention. In other long-term (6 to 12 month) aerobic exercise training studies, circulating total adiponectin levels did not change in an overweight/obese population
34)or metabolic disorders population
35)during the intervention. In contrast, Weiss et al.
36)reported that circulating total adiponectin levels increased (~17%) dur- Fig. 1
3.4 3.6 3.8 4.0 4.2 4.4 4.6 4.8 5.0
rest 30 60
Time (min)
Adiponectin(ug/ml)
* *
0.6 0.8 1.0 1.2 1.4 1.6
HMW adiponectin(ug/ml)
rest 30 60
Time (min)
2.4 2.6 2.8 3.0 3.2 3.4 3.6 3.8
MLMW adiponectin(ug/ml)
rest 30 60
Time (min)
* *
A
B
C
Moderate-intensity High-intensity
Moderate-intensity High-intensity
Moderate-intensity High-intensity
Fig. 1 Changes in total (A), high-molecular weight (HMW) (B) and middle- plus low-molecular weight (MLWM) (C) adiponectin levels during moderate-intensity aerobic ex- ercise and high-intensity aerobic exercise. *A significant difference between rest and 60 min of high-intensity aerobic exercise (P < 0.05). Values are means ± SE.30)
ing a 12-month aerobic exercise intervention in a normal/
overweight population. Moreover, another study found that a 16-week aerobic exercise intervention increased circulating total adiponectin levels (~5-7%)
37). This dis- crepancy in results between studies can be explained, at least, by the amount of weight loss. The former studies observed a slight weight loss (~1-3.5%), whereas the latter studies observed substantial weight loss (~5-9%).
Therefore, chronic aerobic exercise training itself may have only a minor impact on circulating total adiponectin levels. Aerobic exercise training, accompanied by weight loss, may be effective for achieving an increase in total adiponectin levels. Nevertheless, Balducci et al.
38)report- ed that, despite weight remaining unchanged, 6-month aerobic exercise training increased total adiponectin levels (36%) in patients with type 2 diabetes. In that study, participants performed aerobic exercise at 70-80%
V
・o
2peak intensity, which was relatively higher than that reported in other studies with no change in total adiponec- tin levels
32-35). Therefore, it is possible that high-intensity aerobic exercise training may have a potential effect on improvements in circulating total adiponectin levels.
Few studies have reported the effects of aerobic exer- cise training on adiponectin oligomer levels. O’Leary et al.
31)investigated changes in adiponectin oligomer levels in older insulin-resistant adults during 12 weeks of exer- cise alone or exercise with caloric restrictions. Total adi- ponectin and adiponectin oligomer levels did not change, but the ratio of HMW to total adiponectin levels increased during both interventions. The changes in the ratio of HMW to total adiponectin levels positively correlated with the changes in insulin sensitivity. In a recent study
39), a 7-day aerobic exercise training routine increased HMW adiponectin levels in parallel with an improvement in insulin sensitivity. We observed that 12 weeks of aerobic exercise improved insulin sensitivity, but did not increase HMW adiponectin in obese males (unpublished data).
Additional studies are required to determine whether aer- obic exercise training alters adiponectin oligomer levels.
Conclusion
Aerobic exercise can have a minor effect on circulating adiponectin levels in humans. Aerobic exercise may con- tribute to an improvement in metabolic disorders by mod- ulation of interstitial adiponectin levels
27)and number of adiponectin receptors
40), but not by circulating total adipo- nectin levels. However, it is quite likely that intensity and duration of aerobic exercise affect circulating adiponectin levels. Further studies are expected to clarify whether aerobic exercise alters adiponectin oligomer levels and can help for elucidating exercise-induced improvements in metabolic disorders.
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