Role of Adipocytokines on the Pathogenesis of Atherosclerosis in Visceral Obesity.

Funahashi, Tohru; Nakamura, Tadashi; Shimomura, Iichiro; Maeda, Kazuhisa; Kuriyama, Hiroshi; Takahashi, Masahiko; Arita, Yukuio; Kihara, Shinji; Matsuzawa, Yūji

doi:10.2169/internalmedicine.38.202

Cited by 312 publications

(197 citation statements)

References 15 publications

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“…2,3 In its molecular basis, it has been postulated that secreted bioactive substances derived from white adipose tissues, adipocytokines, would play a role in the development of insulin resistance, dyslipidemia, hypertension, and vascular diseases. 4 In such secreted proteins or peptides, white adipose tissues are known to secrete angiogenic peptides including vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF). Originally, VEGF was identified as an endothelial and vascular smooth muscle cells-derived hormone which stimulates local angiogenesis in response to hypoxia.…”

Section: Introductionmentioning

confidence: 99%

Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education

et al. 2003

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OBJECTIVE:To investigate whether the changes in vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) concentrations before and after weight reduction in Japanese overweight men are associated with changes in body mass index (BMI), visceral, subcutaneous fat, VO 2 and work rate (WR) at ventilatory threshold (VT). DESIGN: Cross-sectional and longitudinal clinical intervention study with exercise education. SUBJECTS: In total, 30 Japanese overweight men (BMI, 29.072.2 kg/m 2 ) and 31 normal-weight men (BMI, 22.571.6 kg/m 2 ) at baseline were enrolled: 30 overweight men (BMI, 29.072.2 kg/m 2 ) were further enrolled into a 6-month exercise program. MEASUREMENTS: Fat distribution evaluated by visceral fat (V) and subcutaneous fat (S) areas measured with computed tomography scanning at umbilical levels, angiogenic peptides including VEGF and bFGF, exercise tests at baseline and after 6 months. RESULTS: In normal-weight and overweight subjects at baseline, VEGF positively correlated with S area (r ¼ 0.350, P ¼ 0.007) but not with V area. In contrast, bFGF negatively correlated with BMI (r ¼ À0.619, Po0.001), S (r ¼ À0.457, Po0.001) and V areas (r ¼ À0.466, Po0.001). By intervention with exercise education, 30 overweight subjects showed reduction in BMI (29.072.2 to 28.072.0, Po0.001), V and S areas, increase in VO 2 and WR at VT, increase in bFGF (9.2175.82-21.277.04 ng/ ml, Po0.001), and no change in VEGF (1.4570.72-1.8870.52 ng/ml, P ¼ 0.016). The stepwise multiple regression analysis revealed that DBMI (b ¼ À6.052) and DVO 2 (b ¼ 2.806) were independently related to DbFGF (Po0.001) and all other variables including DS area, and DV area, and DWR did not enter the equation at significant levels. CONCLUSION: The present study indicated a negative correlation between serum bFGF levels and BMI at baseline as well as an association of DBMI and DVO 2 with DbFGF after exercise intervention. The exercise-induced elevation of bFGF may be beneficial in the prevention of the atherosclerosis in overweight subjects.

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Section: Introductionmentioning

confidence: 99%

Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education

et al. 2003

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“…Adipose tissue was believed to be a fat-storage organ, but it is now acknowledged to be an active participant in energy homeostasis and other physiological functions. Adipose tissue is known to express and secrete a variety of novel adipocytokines that have been implicated in the development of insulin resistance and atherosclerosis (3,4). Dysregulation of adipocytokine production is directly involved in the pathophysiology of the metabolic syndrome, and normalization or elevation of plasma concentrations of some adipocytokines reverses the phenotype of the metabolic syndrome (5,6).…”

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confidence: 99%

Changes of Adiponectin Oligomer Composition by Moderate Weight Reduction

et al. 2005

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Adiponectin affects lipid metabolism and insulin sensitivity. However, adiponectin circulates in three different oligomers that may also have distinct biological functions. We aimed to analyze the role of these oligomers in obesity and lipid metabolism after weight reduction. A total of 17 obese volunteers (15 women and 2 men) participated in a weight reduction program. Individuals were characterized before and after 6 months of a balanced diet. Adiponectin was determined by enzyme-linked immunosorbent assay, and oligomers were detected by nondenaturating Western blot. BMI decreased (35.1 ؎ 1.2 to 32.8 ؎ 1.1 kg/m 2 , P < 0.001), which was associated with an improved metabolite profile. Total adiponectin increased from 5.3 ؎ 0.5 to 6.1 ؎ 0.6 g/ml (P ‫؍‬ 0.076). High (HMW) and medium molecular weight (MMW) adiponectin oligomers significantly increased during weight reduction (HMW: 0.37 ؎ 0.07 to 0.4 ؎ 0.08 g/ml, P ‫؍‬ 0.042; MMW: 2.3 ؎ 0.2 to 2.9 ؎ 0.3 g/ml, P ‫؍‬ 0.007), while low molecular weight (LMW) did not significantly change. Body weight inversely correlated with HMW (r ‫؍‬ ؊0.695, P ‫؍‬ 0.002) and positively with LMW (r ‫؍‬ 0.579, P ‫؍‬ 0.015). Interestingly, HDL cholesterol and HMW were strongly correlated (r ‫؍‬ 0.665, P ‫؍‬ 0.007). Indeed, HMW and free fatty acids before weight reduction predicted ϳ60% of HDL changes during intervention. In conclusion, weight reduction results in a relative increase of HMW/MMW adiponectin and a reduction of LMW adiponectin. Total adiponectin and especially HMW adiponectin are related to circulating HDL cholesterol. Diabetes 54: 2712-2719, 2005

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“…The degree of hypoadiponectinemia is more closely related to the degree of insulin resistance and hyperinsulinemia than to the degree of adiposity (20). Low baseline adiponectin levels predict the development of subsequent diabetes in humans (21), and this reduction is suggested to play a role in the pathogenesis of cardiovascular disease associated with obesity (22,23). It is suggested that adiponectin is a potent insulin enhancer linking adipose tissue and whole-body glucose metabolism (24).…”

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confidence: 99%

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity

Yildiz

Suchard

Wong

et al. 2004

Proc. Natl. Acad. Sci. U.S.A.

322

219

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Ghrelin plays a key role in the regulation of growth hormone secretion and energy homeostasis. Adiponectin is exclusively secreted by adipose tissue and is abundantly present in the circulation, with important effects on metabolism. We studied five lean and five obese young men [ages: 24.2 ؎ 1.0 (lean) and 21.8 ؎ 1.6 (obese) years (difference not significant); body mass indexes: 35.0 ؎ 1.3 and 23.0 ؎ 0.3 kg͞m 2 (P ‫؍‬ 0.01)], sampled blood every 7 min over 24 h, and measured ghrelin, adiponectin, and leptin in 2,070 samples for a total of 6,210 data points. Circulating 24-h ghrelin showed significant ultradian fluctuations and an orderly pattern of release in lean and obese subjects with similar pulsatility characteristics. Plasma adiponectin concentrations were significantly lower in the obese group, with lower pulse height. In contrast to leptin, which is secreted in an orderly manner, the 24-h patterns of adiponectin were not significantly different from random in both the lean and obese groups. We show here that adipocytes can simultaneously secrete certain hormones, such as leptin, in patterns that are orderly, whereas other hormones, such as adiponectin, are secreted in patterns that appear to be random. The cross-approximate entropy statistic revealed pattern synchrony among ghrelin-leptin, ghrelin-adiponectin, and leptinadiponectin hormone time series in the lean and obese subjects. Plasma ghrelin concentrations showed a nocturnal rise that exceeded the meal-associated increases in lean subjects, and this newly identified nocturnal rise was blunted in the obese. We suggest that the blunting of the nocturnal rise of ghrelin is a biological feature of human obesity.

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Role of Adipocytokines on the Pathogenesis of Atherosclerosis in Visceral Obesity.

Cited by 312 publications

References 15 publications

Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education

Serum bFGF levels are reduced in Japanese overweight men and restored by a 6-month exercise education

Changes of Adiponectin Oligomer Composition by Moderate Weight Reduction

Alterations in the dynamics of circulating ghrelin, adiponectin, and leptin in human obesity

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