Aerobic Exercise Training-Induced Decrease in Plasma Visfatin and Insulin Resistance in Obese Female Adolescents

Transcription

1 original research International Journal of Sport Nutrition and Exercise Metabolism, 2010, 20, Human Kinetics, Inc. Aerobic Exercise Training-Induced Decrease in Plasma Visfatin and Insulin Resistance in Obese Female Adolescents Kyu-Jin Lee, Yun-A. Shin, Kyoung-Young Lee, Tae-Won Jun, and Wook Song The purpose of this study was to assess differences in the levels of plasma visfatin among female adolescents and changes in plasma visfatin and insulin resistance in obese female adolescents after 12 wk of aerobic exercise training. Twenty normal-weight female students (body-mass index [BMI] <22.9 kg/m 2 and body fat 29.9) and 18 obese female students (BMI 25 kg/m 2 and body fat 30%) participated in this study. Eleven obese students were assigned to an exercise group and completed a 12-wk aerobic exercise-training program that included four 40- to 50-min sessions per wk with an energy expenditure of kcal/d. Seven obese students were assigned to a control group that received no exercise sessions or dietary restriction. The plasma visfatin levels of obese female adolescents were significantly higher (p <.05) than those of the normal-weight female adolescents. The plasma visfatin levels ( ± ng/ml to ± ng/ml, p <.01) and insulin resistance (p <.05) were significantly reduced after 12 wk of aerobic exercise. The results suggest that aerobic exercise resulting in an energy expenditure of 1,200 1,600 kcal/wk for 12 wk decreases plasma visfatin and insulin resistance in obese female adolescents. Keywords: obesity, metabolism, diabetes The prevalence of overweight and obesity in adolescents has recently been recognized worldwide as a critical health issue (Daley, Copeland, Wright, Roalfe, & Wales, 2006). In particular, obesity is a major inducer of insulin resistance and thus also represents a cause of metabolic complications. Obesity beginning in childhood often continues into adulthood and is a principal cause of high blood pressure, diabetes, and hyperlipidemia, thus increasing the likelihood of associated mortality. Excessive obesity, in particular the accumulation of abdominal visceral fat, causes a variety of diseases. These include hyperlipidemia, high blood pressure, Type II diabetes, and coronary heart disease (Iwashima et al., 2004). Fat tissues generate adipocytokines associated with inflammation and cell metabolism. Adipocytokines are known to adjust the homeostasis of blood pressure and fats via the central actions of leptin, the peripheral action of resistin, and the activity of adiponectin and visfatin in the liver and muscles (Trayhurn & Wood, 2004). Among these, visfatin, which is primarily generated in the visceral fat tissues of obese humans and mice, is a newly discovered adipocytokine. It has been reported previously that visfatin exerts insulin-mimetic effects and directly influences insulin receptors (Berndt et al., 2005; Fukuhara et al., 2005). Lee, Lee, Jun, and Song are with the Institute of Sports Science, Seoul National University, Seoul, Korea. Shin is with the Institute of Sports Science, Dankook University, Cheonan, Korea. Visfatin has been shown to be generated in a variety of tissues, including the visceral adipose tissues, skeletal muscle, liver, bone marrow, and lymphocytes. In particular, it functions as a pre-b-cell colony-enhancing factor that adjusts the generation of cytokine, an insulinresistance stimulator (Ognjanovic et al., 2001). Plasma visfatin levels in diabetic and obese individuals are increased (Chen et al., 2006; Krzyzanowska, Krugluger, et al., 2006) and play a pivotal role in obesity-related insulin resistance. Furthermore, plasma visfatin levels have been shown to be high among obese children, as well as obese adults (Haider, Holzer, et al., 2006; Haider, Schindler, et al., 2006). Growing evidence indicates that aerobic exercise induces the reduction of visceral fat; however, only a limited amount of research has been conducted thus far regarding the effects of exercise on visfatin. Recently, Frydelund-Larsen et al. (2007) demonstrated that exercise increased adipose-tissue visfatin mrna without affecting skeletal-muscle visfatin mrna. In particular, the effects of exercise on circulating adipocytokines are a matter of some controversy. More persuasive than the training effect is the effect induced by weight loss (Hara et al., 2005). Haider, Schindler, et al. (2006) previously showed that blood visfatin concentrations were reduced as a result of weight loss occurring after gastrectomy in very obese individuals. By way of contrast, Krzyzanowska, Friedrich, Walter, Hans, and Guntram (2006) previously published opposite findings, showing that there are diverse opinions regarding changes in plasma visfatin, as well as the weight loss induced by surgery. 275

2 276 Lee et al. Meanwhile, although it was noted in a few studies that exercise positively influenced plasma visfatin levels among Type I and Type II diabetes patients (Brema et al., 2008; Haider, Pleiner, et al., 2006) and obese women (Choi et al., 2007; Sheu et al., 2008), there are many limits to the application of the results of these studies, in which diabetic patients and obese women were targeted. Although there was recently a study analyzing plasma visfatin concentrations in nondiabetic obese children (Haider, Holzer, et al., 2006), currently no study has been reported on adolescents, at whose age early-onset Type II diabetes and metabolic syndrome are dramatically increasing. Evidence verifying the effects of exercise on adolescents is also lacking. Thus, this study was designed to verify the differences in blood visfatin concentrations depending on the presence of obesity among female adolescents. We also sought to evaluate the changes in insulin resistance, as well as plasma visfatin, among obese female adolescents as the result of 12 weeks of aerobic exercise. Participants Methods Participants (female high school students) were recruited in this study for an exercise intervention program for obese students in the city of Incheon, Korea. Twenty nonobese female adolescents (age ± 0.69 years, body-mass index [BMI] ± 1.72 kg/m 2 ) and 18 obese female adolescents (age ± 0.89 years, BMI ± 1.89 kg/m 2 ) participated in the study. Obesity was defined as a BMI greater than 25 and body fat in excess of 30%, in accordance with the Asia-Pacific standards (The Asia- Pacific Perspective, 2000). The criteria for participation in the study included no history of cardiovascular disease, no prior use of prescription medications, no history of smoking, and no regular exercise. Obese participants were randomly separated into two groups (aerobic-exercise training group n = 11, control group n = 7). Informed consent was obtained from all participants before the start of the study. The institutional review board of the Institute of Sports Science of Seoul National University approved this study, which followed the Helsinki Declaration. Participants heights were measured on a portable Stationmaster to an accuracy of ± 0.5 cm. Their weights were measured on an Inbody 3.0 system (Biospace, Korea) to the nearest 0.1 kg. VO 2max was measured before and after the training period using the Åstrand protocol with a cycle ergometer and a Vmax ST system (Sensor- Medics Corp., USA). Aerobic Exercise Training Aerobic exercise training was supervised by an experienced physical education instructor and conducted 4 days/week for 12 weeks. Each session consisted of 5 min of warming up, min of rope skipping (the energy expenditure was kcal per exercise session, calculated by measuring heart rate during exercise using the Polar system, Finland), and 5 min of cooling down. The rope-skipping program started at 40% of observed maximal heart rate and gradually increased to 60 80% of maximal heart rate. Blood-Sample Analysis Blood samples were collected before and after the training period at 48 hr after the last bout of exercise to exclude acute effects of exercise. Blood samples were drawn from the median cubital vein after an 11-hr overnight fast. Serum aliquots were stored at 80 C until analysis. Plasma total cholesterol, HDL cholesterol, and triglycerides were measured using an auto-analyzer (COBAS integra 800, Roche, Switzerland) with an enzymatic colorimetric method. Plasma glucose was measured with a radioimmunoassay kit (Linco, USA) with a glucose oxidase technique. Insulin was determined by radioimmunoassay (Gamma counter, Cobra II, USA). Plasma visfatin was assessed using a microplate reader (V-Max 220 VAC ELISA reader, Molecular Devices, USA) with a visfatin C-terminal EIA (Phoenix Pharmaceuticals Inc., Sweden). This enzyme immunoassay kit is designed to detect a specific peptide (visfatin) and its related peptides based on the principle of competitive enzyme immunoassay. Significant sensitivity of EIA was set at 2.53 ng/ ml in the range of 0.1 1,000 ng/ml. Before and after the intervention, insulin resistance in the fasting state was evaluated for all participants via the homeostasis model of insulin-resistance assessment (Matthews et al., 1985). Nutrition Analysis Dietary-intake-recording sheets were distributed to the participants for 1 week to conduct nutritional education and record dietary intake for a total of 3 days, including 2 days after conducting the education and 1 day on the weekend. Dietary intake was investigated using estimated food records. The date of dietary intake, day, food types consumed in each meal, the food materials, and the relevant amounts of foods were all required information on the sheets. Total energy expenditure and nutritional intakes including carbohydrate, protein, and fat were obtained before and after training. For the dietary-intake data analysis, we used a computer-aided nutrient-analysis program developed by the affiliated nutritional information center of the Korean Nutrition Society to determine the nutrient and total energy intake. Statistical Analysis The results were expressed as M ± SD using the SPSS/ PC statistics program (version 12.5 for Windows; SPSS, Inc., Chicago, IL). Student s t test was used to determine the significant differences within the group, and comparisons between groups were analyzed via independent t test. Pearson s correlation analysis was used to analyze bivariate relationships. Two-way ANOVA with repeated

3 Exercise Training, Visfatin, and Obese Adolescents 277 measures for time (pre- and postintervention) and group (obese and nonobese) was used to determine significant differences between group and training. Differences were considered statistically significant at p <.05. Results Participant characteristics are shown in Table 1. All obesity-related factors except total cholesterol were significantly different between obese and nonobese adolescents. In particular, obese students had higher plasma visfatin levels than the nonobese students ( ± ng/ml vs ± ng/ml, p =.015). Table 2 shows that plasma visfatin levels were associated with BMI, body fat, and waist circumference as determined by Pearson s correlation analysis. However, we could not observe any significant relationship among weight, total cholesterol, triglycerides, HDL cholesterol, glucose, insulin, the homeostasis model of insulinresistance assessment, VO 2max, and plasma visfatin levels in obese and nonobese adolescents. Changes in the physical characteristics and plasma lipids of the obese participants after 12 weeks of exercise training are shown in Table 3. Body weight, BMI, waist circumference, total cholesterol, and triglycerides all decreased significantly after 12 weeks of exercise training. Interaction effects between group and time in terms of body weight, BMI, body fat, and VO 2max were observed, but not for other factors. VO 2max of the control obese group was significantly decreased (23.98 ± 1.98 to ± 2.00) after the 12-week training period, whereas other physical characteristics and lipid profiles were unchanged. Changes in the levels of plasma visfatin, glucose, insulin resistance, and insulin in the obese adolescents after 12 weeks of exercise training are provided in Table 4. Visfatin, insulin, and insulin resistance were reduced significantly after 12 weeks of exercise training. Interaction effects between group and time with regard to visfatin, glucose, insulin, and insulin resistance were observed. The changes in nutrient intake as a result of exercise training are provided in Table 5. We noted no significant changes between the exercise group and the control group. Discussion In the current study, we showed that aerobic exercise training with weight loss can reduce plasma visfatin and insulin-resistance levels in obese female adolescents. Recently, insulin resistance, the common pathogenesis of obesity and Type II diabetes, has become the focus of a great many studies. Conventionally, fat tissues are described as active endocrine organs that generate adipocytokines (Havel, 2002; Pittas, Joseph, & Greenberg, 2004), and adipocytokines are generally thought to represent possible connection chains between obesity and insulin resistance (Koerner, Kratzsch, & Kiess, 2005). Adipocytokines are generally increased in the obese, either intervening with or exacerbating a variety of metabolic diseases including insulin resistance (Pittas et al., 2004). Visfatin, which is correlated significantly with insulin resistance, is usually higher among obese and diabetic individuals than those who are not obese (Chen et al., 2006; Haider, Schindler, et al., 2006; Krzyzanowska, Krugluger, et al., 2006), so a host of studies are currently under way concerning the physiological variables associated with obesity and diabetes. Plasma visfatin tends to be increased among individuals with diabetes and obesity (Chen et al., 2006; Haider, Schindler, et al., 2006; Krzyzanowska, Krugluger, et al., Table 1 Physical Characteristics and Physiological Variables in Obese and Nonobese Adolescents, M ± SD Obese (n = 18) Nonobese (n = 20) p Age (years) ± ± 0.69 Height (cm) ± ± 5.23 Weight (kg) ± ± Body-mass index (kg/m) ± ± Muscle (%) ± ± Body fat (%) ± ± Waist circumference (cm) ± ± Total cholesterol (mg/dl) ± ± Triglycerides (mg/dl) ± ± HDL cholesterol (mg/dl) ± ± Glucose (mg/dl) ± ± Insulin (μiu/ml) ± ± HOMA-IR 5.57 ± ± Visfatin (ng/ml) ± ± VO 2max (ml kg 1 min 1 ) ± ± Note. HOMA-IR = homeostasis model of assessment of insulin resistance.

4 278 Lee et al. Table 2 Correlation Between Plasma Visfatin and Physiological Variables Before Exercise Training in Obese and Nonobese Adolescents (N = 38) Correlation coefficient p Weight (kg) Body-mass index (kg/m) * Body fat (%) * Waist circumference (cm) * Total cholesterol (mg/dl) Triglycerides (mg/dl) HDL cholesterol (mg/dl) Glucose (mg/dl) Insulin (μiu/ml) HOMA-IR VO 2max (ml kg 1 min 1 ) Note. HOMA-IR = homeostasis model of assessment of insulin resistance. *Significantly different from before training in group (p <.05). 2006) and plays a role in insulin resistance associated with obesity. In a study targeting a variety of age groups, visfatin level demonstrated a positive relationship with BMI, an index by which obesity and body-fat percentage are measured (Berndt et al., 2005), and even among Type II diabetes patients, it showed a significant positive correlation with BMI and waist circumference (Chen et al., 2006). In a study conducted by Haider, Holzer, et al. (2006) involving children, the correlation between visfatin and BMI was not profound, but visfatin was more than twice as high in the obese children than in the normal-weight adolescents. The obese female adolescents who participated in the current study had significantly higher plasma visfatin levels than the nonobese participants. The same findings as in previous research were seen in this study the level of visfatin among obese adolescents was higher than that measured in the normalweight adolescents (Berndt et al., 2005; Chen et al., 2006; Haider, Holzer, et al., 2006). Furthermore, blood lipid profiles including triglycerides, HDL cholesterol, and the homeostasis model of insulin-resistance assessment in obese adolescents were significantly different than in nonobese participants in this study. Aerobic-exercise training positively influences diabetic and obese participants who show high risk factors in serum lipids and cardiovascular status by increasing insulin sensitivity (Lehmann, Kaplan, Bingisser, Bloch, & Spinas, 1997; Yokoyama et al., 2004). However, the effects of exercise training on adipocytokines varied depending on its intensity and duration, as well as alterations in body composition. In particular, the effects of exercise on circulating adipocytokines have been a source of considerable controversy. Plasma leptin was correlated with insulin concentrations and has been shown in some studies to be reduced by exercise (Ishii et al., 2001; Pasman, Westerterp-Plantenga, & Saris, 1998) and in some to be unaffected by it (Desgorces, Chennaoui, Gomez-Merinno, Drogou, & Guezennec, 2004; Noland et al., 2001). With regard to the negative correlation of adiponectin with body and/or visceral fat, some studies reported no change after a variety of exercise regimens (Hara et al., 2005; Hulver et al., 2002), some reported an increase (Hotta et al., 2000, Kriketos et al., 2004), and some reported a decrease (Yatagai et al., 2003), possibly because of different types, intensities, frequencies, and durations of exercise. However, the effect resulting from weight loss is far less controversial than the putative effects of exercise (Hara et al., 2005). In this study, the group of exercising obese individuals who underwent no changes in their dietary consumption demonstrated a significant increase in maximum oxygen uptake after long-term aerobic exercise. As such, in cases in which the effect of exercising was verified, the plasma visfatin concentration levels were reduced significantly. This is consistent with previous research findings that plasma visfatin concentrations were reduced as the result of long-term exercise among Type I diabetic patients (Haider, Pleiner, et al., 2006), Type II diabetic patients (Brema et al., 2008), and obese women (Choi et al., 2007; Sheu et al., 2008). Plasma visfatin tended to be reduced as the result of long-term exercise (Brema et al., 2008; Choi et al., 2007; Haider, Pleiner, et al., 2006; Sheu et al., 2008), unlike the contrasting results regarding changes in plasma visfatin as the result of artificial weight loss, including surgery conducted on excessively obese individuals (Haider, Schindler, et al., 2006; Krzyzanowska, Friedrich, et al., 2006). Until now, few studies have been conducted regarding the long-term effects of exercise on plasma visfatin among obese participants. In the current study, changes in plasma visfatin concentration in obese adolescents with relatively low risk of metabolic syndrome dramatically decreased (37.1%) after exercise training to the levels of nonobese participants, as compared with adults (7.8% decrease) reported in a previous study (Choi et al., 2007). This demonstrates that the effect of exercise on plasma visfatin levels in obese adolescents is presumably quite high. The mechanism controlling the generation of visfatin has yet to be determined, but some researchers (Haider, Schaller, et al., 2006) have sought answers regarding the relationship between changes in visfatin levels and changes in insulin and glucose levels, based on the high levels of correlation between visfatin and insulin resistance (Fukuhara et al., 2005). In this study, glucose level showed significant changes both before and after 12 weeks of aerobic exercise. However, because it was measured within an ordinary range (glucose mg/ dl), it proved difficult to attach any significance to the physiological changes. Nonetheless, owing principally to the positive changes in insulin levels occurring both before and after the 12-week-long aerobic exercise regimen, the insulin-resistance levels in the exercise group were improved greatly, and further investigation to elucidate the relationship between improved insulin

5 Table 3 Changes in Physical Characteristics and Plasma Lipids With Exercise Training, M ± SD Group Pretraining Posttraining Group Time Weight (kg) F = 8.16, p =.011 exercise (n = 11) ± ± 6.55** control (n = 7) ± ± 8.27 Body-mass index (kg/m) F = 9.093, p =.008 exercise ± ± 1.53** control ± ± 1.66 Muscle (%) F = 2.460, p =.136 exercise ± ± 2.12 control ± ± 2.25 Body fat (%) F = 5.631, p =.031 exercise ± ± 3.66 control ± ± 3.63 Waist circumference (cm) F = 2.894, p =.108 exercise ± ± 5.30* control ± ± 3.05 VO 2max (ml kg 1 min 1 ) F = 8.618, p =.010 exercise ± ± 4.02* control ± ± 2.00* Total cholesterol (mg/dl) F = 2.360, p =.144 exercise ± ± 16.74* control ± ± Triglycerides (mg/dl) F = 0.064, p =.803 exercise ± ± 26.78** control ± ± HDL cholesterol (mg/dl) F = 0.032, p =.860 exercise ± ± 6.09 control ± ± 8.27 *Significantly different from before training in group (p <.05). **Significantly different from before training in group (p <.01). Significant difference between group and training (p <.05). Table 4 Changes in Plasma Visfatin, Glucose, Insulin Resistance, and Insulin With Exercise Training, M ± SD Group Pretraining Posttraining Group Time Visfatin (ng/ml) F = 3.280, p =.049 exercise (n = 11) ± ± 67.30** control (n = 7) ± ± Glucose (mg/dl) F = 4.582, p =.048 exercise ± ± 3.88* control ± ± 4.12* Insulin (μiu/ml) F = 8.691, p =.009 exercise ± ± 3.42* control ± ± 4.10 HOMA-IR F = , p =.002 exercise 6.79 ± ± 1.30* control 4.02 ± ± 1.53 HOMA-IR = homeostasis model of assessment of insulin resistance. *Significantly different from before training in group (p <.05). **Significantly different from before training in group (p <.01). Significant difference between group and training (p <.05). 279

6 280 Lee et al. Table 5 Changes in Nutrient Intake With Exercise Training, M ± SD Group Pretraining Posttraining Group Time Energy (kcal) F = 0.199, p =.662 exercise (n = 11) 1,954.3 ± ,063.9 ± control (n = 7) 1,948.7 ± ,992.1 ± Carbohydrate (g) F = 0.383, p =.545 exercise ± ± 24.3 control ± ± 37.1 Protein (g) F = 0.002, p =.961 exercise 76.0 ± ± 10.6 control 73.8 ± ± 9.2 Fat (g) F = 0.013, p =.911 exercise 62.7 ± ± 12.6 control 60.3 ± ± 14.5 resistance and reduced plasma visfatin level with a large number of participants in the exercise intervention group is recommended. With the exception of the studies conducted by Choi et al. (2007) and Sheu et al. (2008), it is difficult to draw any definitive conclusion regarding changes in plasma visfatin levels for obese women because of the lack of preceding studies associated with changes in visfatin levels for obese women after long-term exercise. In addition, future study will be needed to determine whether the change in plasma visfatin levels is independent of the change in body composition associated with the exercisetraining intervention. In the current study, we determined that plasma visfatin and insulin-resistance levels were reduced after aerobic-exercise training coupled with weight loss. These results indicate that aerobic exercise may exert a significant effect on plasma visfatin and insulin resistance in obese female adolescents. Acknowledgments This work was supported by Korea Science and Engineering Foundation Grant KOSEF-R (W. Song). References The Asia-Pacific Perspective. (2000). Redefining obesity and its treatment. Sydney, Australia: Health Communications Australia. Berndt, J., Kloting, N., Kralisch, S., Kovacs, P., Fasshauer, M., Schon, M.R.,... Blüher, M. (2005). Plasma visfatin concentrations and fat depot-specific mrna expression in humans. Diabetes, 54, Brema, I., Hatunic, M., Finucane, F., Burns, N., Nolan, J.J., Haider, D.,... Ludvik, B. (2008). Plasma visfatin is reduced after aerobic exercise in early onset Type 2 diabetes mellitus. Diabetes, Obesity & Metabolism, 10(7), Chen, M.P., Chung, F.M., Chang, D.M., Tsai, J.C., Huang, H.F., Shin, S.J.,... Lee, Y-J. (2006). Elevated plasma level of visfatin/pre-b cell colony-enhancing factor in patients with Type 2 diabetes mellitus. The Journal of Clinical Endocrinology, 91, Choi, K.M., Kim, J.H., Cho, G.J., Baik, S.H., Park, H.S., & Kim, S.M. (2007). Effect of exercise training on plasma visfatin and eotaxin levels. European Journal of Endocrinology, 157(4), Daley, A.J., Copeland, R.J., Wright, N.P., Roalfe, A., & Wales, J.K. (2006). Exercise therapy as a treatment for psychopathologic conditions in obese and morbidly obese adolescents: A randomized, controlled trial. Pediatrics, 118, Desgorces, F.D., Chennaoui, M., Gomez-Merino, D., Drogou, C., & Guezennec, C.Y. (2004). Leptin response to acute prolonged exercise after training in rowers. European Journal of Applied Physiology, 91(5-6), Frydelund-Larsen, L., Akerstrom, T., Nielsen, S., Keller, P., Keller, C., & Pedersen, B.K. (2007). Visfatin mrna expression in human subcutaneous adipose tissue is regulated by exercise. American Journal of Physiology. Endocrinology and Metabolism, 292(1), E24 E31. Fukuhara, A., Matsuda, M., Nishizawa, M., Segawa, K., Tanaka, M., Kishimoto, K.,... Shimomura, I. (2005). Visfatin: A protein secreted by visceral fat that mimics the effects of insulin. Science, 307, Haider, D.G., Holzer, G., Schaller, G., Weghuber, D., Widhalm, K., Wagner, O.,... Wolzt, M. (2006). The adipokine visfatin is markedly elevated in obese children. Journal of Pediatric Gastroenterology and Nutrition, 43(4), Haider, D.G., Pleiner, J., Francesconi, M., Wiesinger, G.F., Muller, M., & Wolzt, M. (2006). Exercise training lowers plasma visfatin concentrations in patients with Type I diabetes. The Journal of Clinical Endocrinology and Metabolism, 91(11), Haider, D.G., Schaller, G., Kapiotis, S., Maier, C., Luger, A., & Wolzt, M. (2006). The release of the adipocytokine visfatin is regulated by glucose and insulin. Diabetologia, 49, Haider, D.G., Schindler, K., Schaller, G., Prager, G., Wolzt, M., & Ludvik, B. (2006). Increased plasma visfatin concentrations in morbidly obese subjects are reduced after gastric banding. The Journal of Clinical Endocrinology and Metabolism, 91,

7 Exercise Training, Visfatin, and Obese Adolescents 281 Hara, T., Fujiwara, H., Nakao, H., Mimura, T., Yoshikawa, T., & Fujimoto, S. (2005). Body composition is related to increase in plasma adiponectin levels rather than training in young obese men. European Journal of Applied Physiology, 94, Havel, P.J. (2002). Control of energy homeostasis and insulin action by adipocyte hormones: Leptin, acylation stimulating protein, and adiponectin. Current Opinion in Lipidology, 13, Hotta, K., Funahashi, T., Arita, Y., Takahashi, M., Matsuda, M., Okamoto, Y.,... Matsuzawa, Y. (2000). Plasma concentrations of a novel, adipose-specific protein, adiponectin, in Type 2 diabetic patients. Arteriosclerosis, Thrombosis, and Vascular Biology, 20(6), Hulver, M.W., Zheng, D., Tanner, C.J., Houmard, J.A., Kraus, W.E., Slentz, C.A.,... Dohm, G.L. (2002). Adiponectin is not altered with exercise training despite enhanced insulin action. American Journal of Physiology. Endocrinology and Metabolism, 283(4), E861 E865. Ishii, T., Yamakita, T., Yamagami, K., Yamamoto, T., Miyamoto, M., Kawasaki, K.,... Fujii, S. (2001). Effect of exercise training on serum leptin levels in Type 2 diabetic patients. Metabolism: Clinical and Experimental, 50(10), Iwashima, Y., Katsuya, T., Ishikawa, K., Ouchi, N., Ohishi, M., Sugimoto, K.,... Ogihara, T. (2004). Hypoadiponectinemia is an independent risk factor for hypertension. Hypertension, 43, Koerner, A., Kratzsch, J., & Kiess, W. (2005). Adipocytokines: Leptin the classical, resistin the controversial, adiponectin the promising, and more to come. Best Practice and Research Clinical Endocrinology and Metabolism, 53(2), Kriketos, A.D., Gan, S.K., Poynten, A.M., Furler, S.M., Chisholm, D.J., & Campbell, L.V. (2004). Exercise increases adiponectin levels and insulin sensitivity in humans. Diabetes Care, 27(2), Krzyzanowska, K., Friedrich, M., Walter, K., Hans, P.K., & Guntram, S. (2006). Increase in visfatin after weight loss induced by gastroplastic surgery. Obesity (Silver Spring, Md.), 14, Krzyzanowska, K., Krugluger, W., Mittermayer, F., Rahman, R., Haider, D., Shnawa, N., & Schernthaner, G. (2006). Increased visfatin concentrations in women with gestational diabetes. Clinical Science (London), 110, Lehmann, R., Kaplan, V., Bingisser, R., Bloch, K.E., & Spinas, G.A. (1997). Impact of physical activity on cardiovascular risk factors in IDDM. Diabetes Care, 20(10), Matthews, D.R., Hosker, J.P., Rudenski, A.S., Naylor, B.A., Treacher, D.F., & Turner, R.C. (1985). Homeostasis model assessment: Insulin resistance and beta-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia, 28, Noland, R.C., Baker, J.T., Boudreau, S.R., Kobe, R.W., Tanner, C.J., Hickner, R.C.,... Houmard, J.A. (2001). Effect of intense training on plasma leptin in male and female swimmers. Medicine and Science in Sports and Exercise, 33(2), Ognjanovic, S., Bao, S., Yamamoto, S.Y., Garibay-Tupas, J., Samal, B., & Bryant-Greenwood, G.D. (2001). Genomic organization of the gene coding for human pre-b-cell colony enhancing factor and expression in human fetal membranes. Journal of Molecular Endocrinology, 26, Pasman, W.J., Westerterp-Plantenga, M.S., & Saris, W.H. (1998). The effect of exercise training on leptin levels in obese males. The American Journal of Physiology, 274, E280 E286. Pittas, A.G., Joseph, N.A., & Greenberg, A.S. (2004). Adipocytokines and insulin resistance. The Journal of Clinical Endocrinology and Metabolism, 89(2), Sheu, W.H., Chang, T.M., Lee, W.J., Ou, H.C., Wu, C.M., Tseng, L.N.,... Lee, I.T. (2008). Effect of weight loss on proinflammatory state of mononuclear cells in obese women. Obesity (Silver Spring, Md.), 16(5), Trayhurn, P., & Wood, I.S. (2004). Adipocytokines: Inflammation and the pleiotropic role of white adipose tissue. The British Journal of Nutrition, 92, Yatagai, T., Nishida, Y., Nagasaka, S., Nakamura, T., Tokuyama, K., Shindo, M.,... Ishibashi, S. (2003). Relationship between exercise training induced increase in insulin sensitivity and adiponectinemia in healthy men. Endocrine Journal, 50(2), Yokoyama, H., Emoto, M., Araki, T., Fujiwara, S., Motoyama, K., Morioka, T.,... Nishizawa, Y. (2004). Effect of aerobic exercise on plasma adiponectin levels and insulin resistance in Type 2 diabetes. Diabetes Care, 27(7),