Increase In Serum Adiponectin Concentration Research Articles

PO9-213 MYELOPEROXIDASE OXIDIZED-LDL AND TNF-ALPHA ACT IN SYNERGY IN THE TRIGGERING OF INFLAMMATORY RESPONSE

A variety of adipocytokines and peptides secreted from adipocytes have been considered to play a crucial role in obesity, insulin resistance, and type 2 diabetes. Recently, visfatin, a new adipocytokine, known as a pre-B cell colony-enhancing factor, has been isolated from visceral fat deposits. It has been shown to activate insulin receptors in a manner different from insulin. To understand the role of adipocytokines in improving insulin sensitivity via activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) and -γ (PPAR-γ), we examined the expression of visfatin, adiponectin, and TNF-α in visceral fat depots of Otsuka Long–Evans Tokushima fatty (OLETF) rats from early to advanced diabetic stage (from 28 to 40 weeks of age). Serum glucose and insulin concentrations significantly (P < 0.05) decreased in rosiglitazone or fenofibrate-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone significantly increased serum adiponectin concentration from 20 to 40 weeks of age (P < 0.05), whereas fenofibrate reduced TNF-α concentration. The expression of visfatin and adiponectin mRNA in visceral fat deposits was elevated by rosiglitazone or fenofibrate treatments when compared to untreated OLETF rats (P < 0.05), whereas, TNF-α mRNA was down-regulated by these drugs (P < 0.05). These results suggest that rosiglitazone and fenofibrate may prevent type 2 diabetes by regulating adipocytokines including visfatin, adiponectin, and TNF-α.

Increase in serum adiponectin concentration in patients with heart failure and cachexia: relationship with leptin, other cytokines, and B-type natriuretic peptide

Adiponectin is a fat-derived hormone involved in the regulation of metabolism. Adiponectin concentration is inversely related to body weight and, in animals, causes weight loss. We, therefore, measured adiponectin concentration in patients with heart failure (HF) and cachexia. Serum adiponectin concentrations were measured in three groups of patients with coronary artery disease (CAD): (i) HF, reduced left ventricular systolic function, and cachexia (n = 10); (ii) HF, reduced systolic function but no cachexia (n = 20); (iii) HF-controls-patients with CAD, no HF, and preserved systolic function (n = 10); and in a healthy control group (n = 7). Patients with HF and cachexia had higher concentrations of adiponectin [23.8 (10.2-37.2) microg/mL] than all other groups: HF-no cachexia 8.1 (0.5-16.6) microg/mL; CAD-controls 7.1 (0.4-13.5) microg/mL; and healthy controls 8.7 (2.5-16.8) microg/mL) (P < 0.05 for each comparison). Adiponectin correlated negatively with body mass index, percentage of body fat, waist circumference and insulin resistance, and positively with B-type natriuretic peptide (BNP) and tumour necrosis factor-alpha. Cachexia in HF is associated with an increase in adiponectin concentration. This may represent preservation of the physiological response to change in body fat but might also suggest that adiponectin plays a role in the pathogenesis of cachexia. The correlation between BNP and adiponectin also raises the possibility that the former might increase the secretion of the latter.

Peroxisome proliferated-activated receptor γ ligand, Pioglitazone, does not prevent hepatic fibrosis in mice

During hepatic fibrogenesis, quiescent hepatic stellate cells (HSCs) undergo phenotypic transformation into activated matrix-producing cells. This process is recapitulated in primary HSCs cultured on plastic. Based on studies in rats, peroxisome proliferator-activated receptor gamma (PPARgamma) has been suggested to play a key role in the control of HSC activation. Indeed, in rats, PPARgamma expression is depleted in activated HSCs. PPARgamma ligands inhibit HSC activation and prevent hepatic fibrosis in vivo. Here we evaluated the impact of PPARgamma agonists on hepatic fibrogenesis in mice both in vitro and in vivo. Primary HSCs from Balb/C mice were cultured with PPARgamma ligands Pioglitazone (PGZ) or 15-deoxy-Delta12,14 prostaglandin J2 (15d-PGJ2). PPARgamma mRNA expression was stable during culture-activation of HSCs. However, PPARgamma protein was only found in quiescent HSCs but not in fully activated cells. Exposure of HSCs to PPARgamma agonists maintained the expression of PPARgamma, and transactivated this transcription factor as demonstrated by gelshift assay and by induction of CD36, a PPARgamma-regulated gene. However, PPARgamma ligands did not alter the induction of Collagen-I mRNA or alpha-smooth muscle actin (alpha-SMA) in cultured HSCs. To test the effect of PPARgamma agonist PGZ in vivo, hepatic fibrosis was evaluated in Balb/C or C57BL6/J mice treated with CCl4 (three times a week for 4 weeks; or corn oil for controls), and fed a normal or a PGZ-supplemented diet (0.01% wt/wt). PGZ treatment was associated with increased serum adiponectin concentrations but did not decrease the severity of hepatic fibrosis induced by CCl4. Our data demonstrate that, although having anti-fibrotic properties in rats, PPARgamma agonists do not prevent activation of HSCs in vitro, nor hepatic fibrogenesis in vivo in mice.

Effect of Endurance Exercise Training on Serum Adiponectin Concentration

Adiponectin, a cytokine released by adipose tissue, has insulin-sensitizing and anti-atherosclerotic properties. PURPOSE: Since circulatory concentrations of adiponectin are typically lower in obese subjects, this study was performed to determine if endurance exercise training-induced reduction of adiposity resulted in increased serum adiponectin concentration in a sample of black and white men and women aged 17 to 65 years (n=667). METHODS: Serum adiponectin concentrations from before and after a 20-week endurance exercise program were analyzed via enzyme-linked immunoassay. RESULTS: After adjustment for age, serum adiponectin at baseline was not related to VO2max in any race/sex group (range: r=−0.153 in black men, r=−0.016 in white women, p>0.05). Unexpectedly, although mean subcutaneous and intra-abdominal fat area decreased, adiponectin decreased with exercise training (before vs. after: 7.45±0.18 vs. 6.39±0.17 ugmL1, p<0.001). Training-induced change in intra-abdominal fat area was not related to change in adiponectin (r=−0.009, p>0.05). Changes in fat mass and subcutaneous abdominal fat area were inversely related to serum adiponectin change (r=−0.107 and −0.098, respectively, p<0.05), i.e., a larger reduction in adiposity was associated with a slightly smaller decrease in adiponectin. These relationships were small and only significant in black women and white men. In addition, change in VO2max was not related to adiponectin change in any of the race/sex groups (overall r=−0.055, p>0.05). At baseline, adiponectin was related to fasting insulin concentration (r=−0.264, p<0.001) and insulin sensitivity derived from minimal modeling following an intravenous glucose tolerance test (r=+0.266, p<0.001). Although fasting insulin decreased and insulin sensitivity increased in response to exercise training, changes in neither of these vabiables were related to the decrease in adiponectin (r=−0.006 and −0.017, respectively, p>0.05). CONCLUSIONS: Although adiposity decreased slightly, twenty weeks of exercise training resulted in an unexpected decrease in serum adiponectin concentration. Relationships between changes in adiposity indices and adiponectin were very modest. Furthermore, since insulin sensitivity increased in spite of the decrease in adiponectin, adiponectin does not appear to play a major role in the improved insulin sensitivity found with exercise training. Funded by the American Heart Association (Mid-Atlantic Affiliate) and multiple grants from NIH-NHLBI.

Paradoxical rise in serum adiponectin concentration in the face of acid-induced insulin resistance 13-cis-retinoic

We previously reported that treatment of acne with 13-cis-retinoic acid causes insulin resistance and disturbances in lipid metabolism resembling those of the insulin-resistance syndrome. It is not known whether this is associated with alterations in the concentrations of serum adiponectin, an insulin-sensitising hormone secreted by adipocytes. Eleven men (age 24+/-2 years, BMI 22.1+/-0.9 kg/m(2)) received 13-cis-retinoic acid (Roaccutan) treatment for acne for an average of 5 months. The insulin sensitivity of the subjects and concentrations of serum adiponectin were measured before, during and 1 month after the treatment by a euglycaemic-hyperinsulinaemic clamp and ELISA, respectively. There was a reversible reduction in whole-body insulin sensitivity during therapy with 13-cis-retinoic acid. This was associated with a transient 34% increase in serum adiponectin concentration (from 5.3+/-0.9 to 7.1+/-1.2 mug/ml, p<0.05), with a return to pretreatment levels by 1 month after the end of therapy. In the pretreatment study, as well as in the study performed 1 month after the end of therapy, there was a small yet significant decrease in serum adiponectin concentration during a 4-h euglycaemic-hyperinsulinaemic clamp. This decrease was not observed in the clamp performed during treatment with 13-cis-retinoic acid. There is a paradoxical increase in fasting serum adiponectin concentration during the 13-cis-retinoic acid-induced reduction in insulin sensitivity.

Peroxisome Proliferator–Activated Receptor (PPAR)α Activation Increases Adiponectin Receptors and Reduces Obesity-Related Inflammation in Adipose Tissue

We examined the effects of activation of peroxisome proliferator-activated receptor (PPAR)alpha, PPARgamma, and both of them in combination in obese diabetic KKAy mice and investigated the mechanisms by which they improve insulin sensitivity. PPARalpha activation by its agonist, Wy-14,643, as well as PPARgamma activation by its agonist, rosiglitazone, markedly improved insulin sensitivity. Interestingly, dual activation of PPARalpha and -gamma by a combination of Wy-14,643 and rosiglitazone showed increased efficacy. Adipocyte size in Wy-14,643-treated KKAy mice was much smaller than that of vehicle- or rosiglitazone-treated mice, suggesting that activation of PPARalpha prevents adipocyte hypertrophy. Moreover, Wy-14,643 treatment reduced inflammation and the expression of macrophage-specific genes in white adipose tissue (WAT). Importantly, Wy-14,643 treatment upregulated expression of the adiponectin receptor (AdipoR)-1 and AdipoR2 in WAT, which was decreased in WAT of KKAy mice compared with that in nondiabetic control mice. Furthermore, Wy-14,643 directly increased expression of AdipoRs and decreased monocyte chemoattractant protein-1 expression in adipocytes and macrophages. Rosiglitazone increased serum adiponectin concentrations and the ratio of high molecular weight multimers of adiponectin to total adiponectin. A combination of rosiglitazone and Wy-14,643 increased both serum adiponectin concentrations and AdipoR expression in WAT. These data suggest that PPARalpha activation prevents inflammation in WAT and that dual activation of PPARalpha and -gamma enhances the action of adiponectin by increasing both adiponectin and AdipoRs, which can result in the amelioration of obesity-induced insulin resistance.

Reduced Adiposity in Bitter Melon (Momordica charantia)–Fed Rats Is Associated with Increased Lipid Oxidative Enzyme Activities and Uncoupling Protein Expression

To further explore the antiobesity effect of freeze-dried bitter melon (BM) juice, activities of mitochondrial lipid oxidative enzymes as well as the expression of uncoupling proteins and their transcription coactivator peroxisome proliferator-activated receptor-gamma coactivator-1 alpha (PGC-1alpha) were determined in diet-induced obese (DIO) rats. Rats were fed high-fat (HF) diets to induce obesity, and the effect of BM was assessed at doses of 0.75, 1.0, or 1.25% (wt:wt). In a dose-response experiment, BM-supplemented rats had lower energy efficiency (g weight gained/kJ consumed), visceral fat mass, serum glucose, and insulin resistance index, but higher plasma norepinephrine than unsupplemented rats (P < 0.05). Hepatic and skeletal muscle triglyceride concentrations were lower in supplemented HF diet-fed rats than in unsupplemented HF diet-fed rats (P < 0.05). An HF diet supplemented with BM elevated activities of hepatic and muscle mitochondrial carnitine palmitoyl transferase-I (CPT-I) and acyl-CoA dehydrogenase (AD) (P < 0.05). In another experiment, BM (1.0 g/100 g) lowered visceral fat mass but increased serum adiponectin concentration in HF diet-fed rats (P < 0.05). In the final study, rats were fed the HF diet with 0, 1.0 or 1.25% BM. Both groups of BM-supplemented rats had higher uncoupling protein 1 in brown adipose tissue (P < 0.05) and uncoupling protein 3 in red gastrocnemius muscle (P < 0.05), measured by Western blotting and RT-PCR, than the controls. The expression of the transcription coactivator PGC-1alpha in both tissues was also significantly elevated in the BM-supplemented rats (P < 0.05). The present results suggest that decreased adiposity in BM-supplemented rats may result from lower metabolic efficiency, a consequence of increased lipid oxidation and mitochondrial uncoupling.

Effect of PPAR-α and -γ agonist on the expression of visfatin, adiponectin, and TNF-α in visceral fat of OLETF rats

A variety of adipocytokines and peptides secreted from adipocytes have been considered to play a crucial role in obesity, insulin resistance, and type 2 diabetes. Recently, visfatin, a new adipocytokine, known as a pre-B cell colony-enhancing factor, has been isolated from visceral fat deposits. It has been shown to activate insulin receptors in a manner different from insulin. To understand the role of adipocytokines in improving insulin sensitivity via activation of the nuclear receptor peroxisome proliferator-activated receptor-α (PPAR-α) and -γ (PPAR-γ), we examined the expression of visfatin, adiponectin, and TNF-α in visceral fat depots of Otsuka Long–Evans Tokushima fatty (OLETF) rats from early to advanced diabetic stage (from 28 to 40 weeks of age). Serum glucose and insulin concentrations significantly ( P < 0.05) decreased in rosiglitazone or fenofibrate-treated OLETF rats compared to untreated OLETF rats. Rosiglitazone significantly increased serum adiponectin concentration from 20 to 40 weeks of age ( P < 0.05), whereas fenofibrate reduced TNF-α concentration. The expression of visfatin and adiponectin mRNA in visceral fat deposits was elevated by rosiglitazone or fenofibrate treatments when compared to untreated OLETF rats ( P < 0.05), whereas, TNF-α mRNA was down-regulated by these drugs ( P < 0.05). These results suggest that rosiglitazone and fenofibrate may prevent type 2 diabetes by regulating adipocytokines including visfatin, adiponectin, and TNF-α.

Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy

Highly active antiretroviral therapy (HAART) has improved the prognosis of human immunodeficiency virus (HIV)-infected patients but is associated with severe adverse events, such as lipodystrophy and insulin resistance. Rosiglitazone did not increase subcutaneous fat in patients with HAART-associated lipodystrophy (HAL) in a randomized, double-blind, placebo-controlled trial, although it attenuated insulin resistance and decreased liver fat content. The aim of this study was to examine effects of rosiglitazone on gene expression in subcutaneous adipose tissue in 30 patients with HAL. The mRNA concentrations in subcutaneous adipose tissue were measured using real-time PCR. Twenty-four-week treatment with rosiglitazone (8 mg/day) compared with placebo significantly increased the expression of adiponectin, peroxisome proliferator-activated receptor-gamma (PPARgamma), and PPARgamma coactivator 1 and decreased IL-6 expression. Expression of other genes involved in lipogenesis, fatty acid metabolism, or glucose transport, such as acyl-CoA synthase, adipocyte lipid-binding protein, CD45, fatty acid transport protein-1 and -4, GLUT1, GLUT4, keratinocyte lipid-binding protein, lipoprotein lipase, PPARdelta, and sterol regulatory element-binding protein-1c, remained unchanged. Rosiglitazone also significantly increased serum adiponectin concentration. The change in serum adiponectin concentration was inversely correlated with the change in fasting serum insulin concentration and liver fat content. In conclusion, rosiglitazone induced significant changes in gene expression in subcutaneous adipose tissue and ameliorated insulin resistance in patients with HAL. Increased expression of adiponectin might have mediated most of the favorable insulin-sensitizing effects of rosiglitazone in these patients.

Angiotensin II Receptor Blocker Prevents Increased Arterial Stiffness in Patients With Essential Hypertension

High pulse wave velocity (PWV) is related to cardiovascular risk in essential hypertension (EHT). It is reported that short-term treatment with an angiotensin II receptor blocker (ARB) decreases PWV, as well as blood pressure (BP), and increases the serum adiponectin, known as an adipocytokine, which has an anti-atherosclerotic effect. However, it is not known whether long-term treatment with ARB prevents the increase in PWV independently of the reduction of BP, and whether adiponectin is related to the chronic effect of ARB on PWV. In order to examine the short-term effect of ARB on PWV, 9 subjects with EHT had PWV measured before and after treatment with an ARB for 1 month. The treatment significantly reduced PWV and BP. For evaluation of the long-term effect of ARB therapy, 56 consecutive subjects with EHT who were already taking anti-hypertensive drugs other than an angiotensin-converting enzyme inhibitor had their PWV measured. We divided the EHT subjects into 2 groups: (1) the ARB group (EHT treated with an ARB for at least 6 months) and (2) the control group (EHT treated with anti-hypertensive drugs other than an ARB). Although there was no significant difference between the 2 groups in BP, age or body mass index, the PWV value in the ARB group was significantly lower than that in the control group. Moreover, the serum adiponectin concentration in the ARB group was significantly higher than that in the control group. Long-term treatment with ARB inhibits the progression of arterial stiffness independent of BP reduction. One of the mechanisms may be related to the increased serum adiponectin concentration after treatment with an ARB.