Adiponectin Expression In Adipose Tissue Research Articles

1382-P: Novel Mechanisms to Reconvert Glucocorticoids into Pro-Metabolic Agents through Adiponectin

Adiponectin is the most abundant adipokine in our circulation and regulates inter-tissue communication like the adipose-muscle axis. Pharmacological modulation of this crosstalk is beneficial in promoting exercise tolerance in metabolic stress conditions like obesity. Endogenous glucocorticoids regulate metabolic function and stress response, but chronic daily intake of exogenous glucocorticoids produces or exacerbates metabolic stress. However, in stark contrast to daily intake, we discovered that intermittent regimens of glucocorticoids, e.g. once-weekly, improves exercise tolerance. However, the mechanisms underlying the differential regimen-specific effects of glucocorticoids in obesity remain unknown. Here we investigated the mechanisms differentiating once-weekly versus once-daily regimens of the same glucocorticoid prednisone in obesity. In mice with diet-induced obesity, once-weekly prednisone stimulated total and high-molecular weight adiponectin levels, improving exercise tolerance and energy expenditure. These effects were dependent upon adiponectin and were blocked by genetic ablation of the adipokine. Upregulation of Adipoq occurred through the adipose-specific glucocorticoid receptor (GR) , as this effect was blocked in mice with inducible GR ablation in adipose tissue. In contrast, once-daily prednisone decreased adiponectin levels through upregulation of known repressors of adiponectin expression in adipose tissue. The drug regimens remodeled in opposite ways also transcriptome and function in skeletal muscle after onset of obesity. Particularly, once-weekly prednisone treatment increased the muscle metabolic response to adiponectin through the CAMKK2-AMPK cascade. Our study demonstrates that intermittent glucocorticoids produce healthful metabolic remodeling in diet-induced obesity through direct upregulation of adiponectin expression in adipose tissue and adiponectin-dependent signaling in skeletal muscle. Disclosure M.Wintzinger: Employee; Cincinnati Children's Hospital. K.Miz: None. M.Panta: None. H.Durumutla: None. A.Pragasam: None. M.Quattrocelli: None. Funding National Institutes of Health grant DK121875National Institutes of Health grant HL158531CCHMC Trustee AwardCCHMC Heart Institute Translational Grant

DNA aptamer raised against receptor for advanced glycation end products suppresses renal tubular damage and improves insulin resistance in diabetic mice.

Objective:Interaction of advanced glycation end products (AGEs) with the receptor RAGE plays a role in diabetic nephropathy. However, effects of RAGE-aptamer on tubular damage remain unknown. We examined whether RAGE-aptamer inhibited tubular damage in KKAy/Ta mice, obese type 2 diabetic mice with insulin resistance.Materials and Methods:Male 8-week-old KKAy/Ta mice received continuous intraperitoneal infusion of either control-aptamer or RAGE-aptamer for 8 weeks. Blood biochemistry and blood pressure, and urinary N-acetyl-β-D-glucosaminidase (NAG) activity and albumin excretion levels were monitored. Kidney and adipose tissue samples were obtained for immunohistochemical analyses.Results:Although RAGE-aptamer did not affect blood glucose, blood pressure, body weight, or serum creatinine values, it significantly inhibited the increase in urinary NAG activity and HOMA-IR in diabetic mice at 12 and 16 and at 16 weeks old, respectively. Furthermore, compared with control-aptamer-treated mice, renal carboxymethyllysine, RAGE, and NADPH oxidase-driven superoxide generation were significantly decreased in RAGE-aptamer-treated mice at 12 weeks old with subsequent amelioration of histological alterations in glomerular and interstitial area, while adipose tissue adiponectin expression was increased.Conclusion:Our present results suggest that RAGE-aptamer could inhibit tubular injury in obese type 2 diabetic mice partly by suppressing the AGE-RAGE-oxidative stress axis and improving insulin resistance.

Hepatic stearoyl CoA desaturase 1 deficiency increases glucose uptake in adipose tissue partially through the PGC-1α–FGF21 axis in mice

Increased carbohydrate consumption increases hepatic de novo lipogenesis, which has been linked to the development of chronic metabolic diseases, including obesity, hepatic steatosis, and insulin resistance. Stearoyl CoA desaturase 1 (SCD1) is a critical lipogenic enzyme that catalyzes the synthesis of two monounsaturated fatty acids, oleate and palmitoleate, from the saturated fatty acids stearate and palmitate, respectively. SCD1-deficient mouse models are protected against diet-induced adiposity, hepatic steatosis, and hyperglycemia. However, the mechanism of this protection by SCD1 deficiency is unclear. Using liver-specific SCD1 knockout (LKO) mice fed a high-carbohydrate, low-fat diet, we show that hepatic SCD1 deficiency increases systemic glucose uptake. Hepatic SCD1 deficiency enhanced glucose transporter type 1 (GLUT1) expression in the liver and also up-regulated GLUT4 and adiponectin expression in adipose tissue. The enhanced glucose uptake correlated with increased liver expression and elevated plasma levels of fibroblast growth factor 21 (FGF21), a hepatokine known to increase systemic insulin sensitivity and regulate whole-body lipid metabolism. Feeding LKO mice a triolein-supplemented but not tristearin-supplemented high-carbohydrate, low-fat diet reduced FGF21 expression and plasma levels. Consistently, SCD1 inhibition in primary hepatocytes induced FGF21 expression, which was repressed by treatment with oleate but not palmitoleate. Moreover, deletion of the transcriptional coactivator PPARγ coactivator 1α (PGC-1α) reduced hepatic and plasma FGF21 and white adipocyte tissue-specific GLUT4 expression and raised plasma glucose levels in LKO mice. These results suggest that hepatic oleate regulates glucose uptake in adipose tissue either directly or partially by modulating the hepatic PGC-1α-FGF21 axis.

Abstract P049: Circulating Adiponectin Levels and Risk of Type 2 Diabetes, Cardiovascular Disease, and All-Cause Mortality in US Women

Introduction: Adiponectin is an anti-inflammatory peptide hormone secreted by adipocytes and has been related with decreased risk of type 2 diabetes (T2D) and cardiovascular disease (CVD), but longitudinal data are limited and inconsistent. Hypothesis: Higher circulating adiponectin levels are associated with lower risk of T2D, CVD, and all-cause mortality in healthy women. Methods: Baseline adiponectin levels, measured by an immunoassay, were available on 15,131 women from the Nurses’ Health study I and II, who were part of 11 separate nested case-control studies and free of T2D, CVD, and cancer at study baseline. Associations of adiponectin levels with incident T2D, CVD (including coronary heart disease [CHD], stroke, and CVD death), and all-cause mortality were estimated using Cox regressions adjusted for study design characters, established risk factors and confounders including menopausal status, hormone therapy, and continuous body mass index. We also analyzed associations of 26 adiponectin expression-associated variants (in adipose tissue) with T2D, CVD, and all-cause mortality in the UK Biobank study. Results: During up to 22 years (289,408 person-years) of follow-up, 2,578 T2D cases, 1,827 CVD cases (including 745 CHD, 1,108 stroke and 428 CVD deaths), and 2,741 deaths occurred. In multivariable models, hazard ratios (95% confidence intervals) comparing the highest quartile of plasma adiponectin to the lowest were 0.17 (0.14-0.21; P trend <0.001) for T2D, 0.82 (0.69-0.96; P trend =0.005) for CVD, 0.66 (0.51-0.86; P trend <0.001) for CHD, 0.91 (0.73-1.12; P trend =0.34) for stroke, 0.69 (0.48-0.98; P trend =0.10) for CVD death, and 0.77 (0.66-0.90; P trend =0.005) for all-cause mortality. Genetic alleles associated with increased adiponectin expression in adipose tissue were associated with decreased risk of CVD, but no associations were observed for T2D and all-cause mortality. Conclusions: Higher adiponectin levels are associated with decreased risk of cardiometabolic diseases and all-cause mortality.

Shexiang Baoxin Pill Corrects Metabolic Disorders in a Rat Model of Metabolic Syndrome by Targeting Mitochondria.

Background: Metabolic syndrome (MS) is a global epidemic that has great socioeconomic and public health implications. This study reports observed effects of the Shexiang Baoxin Pill (SBP) in a rat model of MS and explores its underlying mechanisms of action.Methods: A diet-induced rat model of MS was established according to accepted methods, and the rats were randomly divided into two groups: a control group (0.9% NaCl, 100 mg/kg•d) and a SBP-treated group (SBP, 100 mg/kg•d). Systolic blood pressures, fasting blood glucose (FBS) levels, triglyceride (TG) levels, high-density lipoprotein cholesterol (HDL-C) levels, body weights, and abdominal perimeters were dynamically monitored and analyzed. Serum leptin, adiponectin, TNF-α, IL-6, and IL-10 levels were measured by ELISA. Leptin, adiponectin, TNF-α, IL-6, and IL-10 expression in adipose tissue, as well as AMP-activated protein kinase (AMPK) and peroxisome proliferator-activated receptor gamma coactivator 1-α (PGC-1α) expression in heart, liver, skeletal muscle, and adipose tissue was measured by western blot. Expression of the mitochondrial protein UCP2, Cytochrome b and ATPase was observed by immunofluorescent staining.Results: SBP significantly decreased serum TG, TC, LDL-C levels and increased HDL-C levels. SBP also optimized the leptin/adiponectin ratio by decreasing leptin expression and increasing adiponectin expression in adipose tissue. SBP antagonized inflammatory reactions by promoting IL-10 expression in adipose tissue while inhibiting TNF-α and IL-6 expression. SBP improved lipid metabolism by up-regulating the expression of AMPK and PGC-1α. Furthermore, SBP decreased the severity of MS and its complications by adjusting the expression of several mitochondrial proteins, including UCP2, Cytochrome b and ATPase.Conclusion: SBP exhibits prominent therapeutic effects in the setting of MS. Possible mechanisms of action may be related to its anti-inflammatory and anti-oxidative characteristics, as well as its effects on improving lipid metabolism and protecting mitochondrial function.

Gender-Associated Impact of Early Leucine Supplementation on Adult Predisposition to Obesity in Rats.

Early nutrition plays an important role in development and may constitute a relevant contributor to the onset of obesity in adulthood. The aim of this study was to evaluate the long-term impact of maternal leucine (Leu) supplementation during lactation on progeny in rats. A chow diet, supplemented with 2% Leu, was supplied during lactation (21 days) and, from weaning onwards, was replaced by a standard chow diet. Then, at adulthood (6 months of age), this was replaced with hypercaloric diets (either with high-fat (HF) or high-carbohydrate (HC) content), for two months, to induce obesity. Female offspring from Leu-supplemented dams showed higher increases in body weight and in body fat (62%) than their respective controls; whereas males were somehow protected (15% less fat than the corresponding controls). This profile in Leu-females was associated with altered neuronal architecture at the paraventricular nucleus (PVN), involving neuropeptide Y (NPY) fibers and impaired expression of neuropeptides and factors of the mTOR signaling pathway in the hypothalamus. Interestingly, leptin and adiponectin expression in adipose tissue at weaning and at the time before the onset of obesity could be defined as early biomarkers of metabolic disturbance, predisposing towards adult obesity under the appropriate environment.

The Beneficial Effect of Anthocyanidin-Rich Vitis vinifera L. Grape Skin Extract on Metabolic Changes Induced by High-Fat Diet in Mice Involves Antiinflammatory and Antioxidant Actions.

We hypothesized that a polyphenol-rich extract from Vitis vinifera L. grape skin (GSE) may exert beneficial effects on obesity and related metabolic disorders induced by a high-fat diet (HFD). C57/BL6 mice were fed a standard diet (10% fat, control, and GSE groups) or an HFD (60% fat, high fat (HF), and HF + GSE) with or without GSE (200 mg/kg/day) for 12 weeks. GSE prevented weight gain; dyslipidemia; insulin resistance; the alterations in plasma levels of leptin, adiponectin, and resistin; and the deregulation of leptin and adiponectin expression in adipose tissue. These beneficial effects of GSE may be related to a positive modulation of insulin signaling proteins (IR, pIRS, PI3K, pAKT), pAMPK/AMPK ratio, and GLUT4 expression in muscle and adipose tissue. In addition, GSE prevented the oxidative damage, evidenced by the restoration of antioxidant activity and decrease of malondialdehyde and carbonyl levels in muscle and adipose tissue. Finally, GSE showed an anti-inflammatory action, evidenced by the reduced plasma and adipose tissue inflammatory markers (TNF-α, IL-6). Our results suggest that GSE prevented the obesity and related metabolic disorders in HF-fed mice by regulating insulin sensitivity and GLUT4 expression as well as by preventing the oxidative stress and inflammation in skeletal muscle and adipose tissue. Copyright © 2017 John Wiley & Sons, Ltd.

Navel orange peel hydroethanolic extract, naringin and naringenin have anti-diabetic potentials in type 2 diabetic rats

The therapy of Type 2 Diabetes Mellitus (T2DM) stays a challenging issue. During the last decade, there has been an interest in the expansion of anti-diabetic drugs especially those of natural sources. Thus, the aim of this study was to assess the anti-hyperglycemic and the anti-hyperlipidemic effects as well as the anti-oxidant activities of navel orange hydroethanolic extract and its constituting flavonoids naringin and naringenin on nicotineamide (NA)/streptozotocin (STZ)-induced type 2 diabetic rats. To induce T2DM, 16h-fasted rats were intraperitoneally injected with STZ at dose of 50mg/kg body weight (b. w.), 15min after the intraperitoneal administration of NA (120mg/kg b. w.). The NA/STZ-induced type 2 diabetic rats were orally treated with navel orange peel hydroethanolic extract, naringin and narengenin at dose level of 100mg/kg b. w./day for 4 weeks. The treatments with navel orange peel hydroethanolic extract, naringin and narengenin potentially alleviated the lowered serum insulin and C-peptide levels, the depleted liver glycogen content, the elevated liver glucose-6-phosphatase and glycogen phosphorylase activities, the deteriorated serum lipid profile, and the suppressed liver antioxidant defense system of NA/STZ-induced type 2 diabetic rats. The treatments also enhanced the mRNA expression of insulin receptor β-subunit, GLUT4 and adiponectin in adipose tissue of STZ/NA-induced type 2 diabetic rats. In conclusion, the navel orange peel hydroethanolic extract, naringin and naringenin have potent anti-diabetic effects in NA/STZ-induced type 2 diabetic rats via their insulinotropic effects and insulin improving action which in turn may be mediated through enhancing insulin receptor, GLUT4 and adiponectin expression in adipose tissue.

Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension.

Perivascular adipose tissue (PVAT)-derived adiponectin (APN) is a secreted adipokine that protects against hypertension-related cardiovascular injury. However, the regulation of APN expression in hypertension remains to be explored. In this study, we demonstrated that down-regulation of APN was associated with complement activation in the PVAT of desoxycorticosterone acetate (DOCA)-salt hypertensive mice. Complement 3-deficient hypertensive mice were protected from ANP decrease in the PVAT. APN deficiency blockaded the protective effects of complement inhibition against hypertensive vascular injury. Mechanistically, complement 5a (C5a)-induced TNF-α secretion from macrophages is required for inhibiting APN expression in adipocytes. Macrophage depletion reversed C5a agonist peptide-induced TNF-α up-regulation and APN down-regulation in the PVAT of DOCA mice. Moreover, we detected increased macrophage infiltration and C5a expression associated with decreased APN expression in adipose tissue from patients with aldosterone-producing adenoma. These results identify a novel interaction between macrophages and adipocytes in the PVAT, where complement-mediated inhibition of APN acts as a potential risk factor for hypertensive vascular inflammation.-Ruan, C.-C., Ma, Y., Ge, Q., Li, Y., Zhu, L.-M., Zhang, Y., Kong, L.-R., Wu, Q-H., Li, F., Cheng, L., Zhao, A. Z., Zhu, D.-L., Gao, P.-J. Complement-mediated inhibition of adiponectin regulates perivascular inflammation and vascular injury in hypertension.

Lactobacillus paracasei subsp. paracasei NTU 101 ameliorates impaired glucose tolerance induced by a high-fat, high-fructose diet in Sprague-Dawley rats

We examined the protective effects of Lactobacillus paracasei subsp. paracasei NTU 101 lyophilized powder (NTU 101) on impaired glucose tolerance (IGT) induced by a high-fat, high-fructose diet. We found that NTU 101 significantly decreased fasting blood glucose, insulin levels, and homeostatic model assessment -insulin resistance scores and improved glucose tolerance. Moreover, NTU 101 increased Bifidobacterium spp. in faeces and restored tight junction protein expression in the colon, thereby reducing serum lipopolysaccharide (LPS) and inflammatory cytokine levels. NTU 101 also promoted glucose transporter expression in peripheral tissues and adiponectin expression in adipose tissue. NTU 101 may ameliorate IGT by improving intestinal microbiota, preserving gut integrity, and inhibiting LPS-induced inflammation, suggesting the potential clinical applications of this bacterium in the prevention of type 2 diabetes mellitus.

Indicators of iron status are correlated with adiponectin expression in adipose tissue of patients with morbid obesity

AimThe aim of this study was to assess interactions between glucose and iron homoeostasis in the adipose tissue (AT) of obese subjects. MethodsA total of 46 obese patients eligible for bariatric surgery were recruited into the study. Anthropometric and biochemical characteristics were assessed, and biopsies of subcutaneous (SCAT) and visceral adipose tissue (VAT) performed. The mRNA levels of genes involved in iron and glucose homoeostasis were measured in their AT and compared with a pool of control samples. ResultsGene expression of hepcidin (HAMP) was significantly increased in the SCAT and VAT of obese patients, while transferrin receptor (TFRC) expression was reduced, compared with non-obese controls, suggesting a higher iron load in obese patients. Also, mRNA levels of adiponectin (ADIPOQ) were decreased in both SCAT and VAT in obese patients, and correlated negatively with hepcidin expression, while adiponectin expression was positively correlated with TFRC expression in both SCAT and VAT. Interestingly, TFRC expression in VAT correlated negatively with several metabolic parameters, such as fasting blood glucose and LDL cholesterol. ConclusionIron content appears to be increased in the SCAT and VAT of obese patients, and negatively correlated with adiponectin expression, which could be contributing to insulin resistance and the metabolic complications of obesity.

The association of bone turnover markers with pro- and anti-inflammatory adipokines in patients with gestational diabetes.

The aim of the study was to assess differences in circulating osteocalcin (OC) and osteoprotegerin (OPG), as well as in their expression in subcutaneous adipose tissue (SAT), visceral adipose tissue (VAT) and placental tissue obtained from patients with gestational diabetes mellitus (GDM) and normal glucose tolerance (NGT). Serum levels of OC, OPG and soluble nuclear factor-kB ligand (sRANKL) were measured in 49 women with GDM and 30 subjects with NGT between weeks 24-32 of gestation, and three months after childbirth. OC and OPG mRNA expression was measured in 23 patients with GDM and 23 women with NGT at term, using quantitative real-time RT-PCR. The patients with GDM had decreased OC mRNA expression in SAT (p=0.015), lower adiponectin mRNA expression in VAT (p=0.039), and a lower circulating adiponectin level (p=0.04). Multiple regression analysis revealed that serum adiponectin was significantly associated with OC mRNA expression in SAT (b=0.49, p=0.03). Three months postpartum, the OPG/sRANKL ratio was markedly higher in the subjects with prior GDM (p=0.03) and correlated positively with HbA1c (R=0.33; p=0.04), fasting insulin (R=0.35; p=0.03) and HOMA-IR (R=0.34; p=0.04). In the patients with GDM decreased OC mRNA expression in SAT might be associated with a reduced stimulatory effect on adiponectin expression in adipose tissue. On the other hand, higher OPG/sRANKL ratio suggests a better protection against bone loss in the subjects with prior GDM.

Cyclocarya paliurus extract modulates adipokine expression and improves insulin sensitivity by inhibition of inflammation in mice

Ethnopharmacological relevanceCyclocarya paliurus Batal., a Chinese native plant, is the sole species in its genus and its leaves have been widely used as a remedy for diabetes in traditional folk medicine. The study was undertaken to evaluate the effects of Cyclocarya paliurus leaves extracts (CPE) on adipokine expression and insulin sensitivity in mice. Materials and methodsMice were stimulated with conditioned medium (prepared from activated macrophages, Mac-CM) to induce adipose dysfunction and insulin resistance. Then mice were treated with CPE (100, 200 and 500mg/kg, ig.) or metformin (200mg/kg, ig.), followed by glucose and insulin intolerance, adipokine expression, phosphorylation of insulin receptor substrate (IRS-1) and glucose consumption measurement. ResultsCPE, as well as metformin effectively promoted glucose disposal in oral glucose tolerance test in normal mice. Mac-CM challenge induced glucose and insulin intolerance, but CPE reversed these alternations with increased glycogen content in muscle and liver, well demonstrating its beneficial effects on glucose homeostasis. RT-qPCR analysis showed that CPE inhibited TNF-a, IL-6, MCP-1 and resistin overexpression and effectively enhanced adiponectin expression in adipose tissue when mice were exposed to Mac-CM stimulation. Inflammation impaired insulin signaling in muscle, whereas CPE inhibited inflammation-induced serine phosphorylation of IRS-1 and effectively restored the phosphorylation of both IRS-1 at tyrosine residues and downstream Akt phosphorylation in response to insulin. Moreover, independently of insulin, CPE promoted glucose consumption in adipocytes under normal and inflammatory conditions. ConclusionAbove-mentioned results demonstrated that CPE beneficially regulated adipokines expression and ameliorated insulin resistance through inhibition of inflammation in mice.

Aggravation of nonalcoholic steatohepatitis by moderate alcohol consumption is associated with decreased SIRT1 activity in rats.

Chronic alcohol intake decreases adiponectin and sirtuin 1 (SIRT1) expressions, both of which have been implicated in various biological processes including inflammation, apoptosis and metabolism. We have previously shown that moderate consumption of alcohol aggravates liver inflammation and apoptosis in rats with pre-existing nonalcoholic steatohepatitis (NASH). This study investigated whether moderate alcohol intake alters SIRT1 activity, adiponectin/Adiponectin receptor (AdipoR)-related signaling and lipid metabolism in a pre-existing NASH status. Sprague-Dawley rats were fed with a high-fat diet (71% energy from fat) for 6 weeks to induce NASH then subsequently divided into 2 sub-groups: fed either a modified high-fat diet (HFD, 55% energy from fat) or a modified high-fat alcoholic diet (HFA, 55% energy from fat and 16% energy from ethanol) for an additional 4 weeks. We observed in comparison to HFD group, HFA increased hepatic nuclear SIRT1 protein but decreased its deacetylase activity. SREBP-1c protein expression and FAS mRNA levels were significantly upregulated, while DGAT1/2 and CPT-I mRNA levels were downregulated in the livers of HFA compared to HFD. Although hepatic AdipoR1 decreased, HFA did not alter AdipoR2 and their downstream signaling. There were no significant changes in plasma adiponectin and free fatty acids (FFA), as well as adiponectin expression in adipose tissue between the two groups. The present study indicates that suppression in SIRT1 deacetylase activity contributes to alcohol-exacerbated hepatic inflammation and apoptosis in rats with pre-existing NASH. In addition, moderate alcohol intake did not modulate adiponectin/AdipoR signaling axis in this model.

Effects of Angiotensin II Type 1 receptor blocker and adiponectin on adipocyte dysfunction in stroke-prone spontaneously hypertensive rats

BackgroundHypoadiponectinemia in lipoatrophy may be related to worsening of hypertension in stroke-prone spontaneously hypertensive rats (SHRSP). One of the beneficial effects of candesartan (Angiotensin II Type 1 receptor blocker) for preventing hypertension may be increasing of adiponectin due to improvement of adipocyte dysfunction. In this study, we determined the effects of candesartan or adiponectin on pathophysiologic features and adipocyte dysfunction in SHRSP.MethodsCandesartan was administered to male SHRSP from 16 to 20 weeks of age (2 mg/kg/day). Adiponectin was cloned and intravenously administered to male SHRSP from 16 to 20 weeks of age. We examined biological parameters, as well as the expression and release of adipokines.ResultsThe SHRSP exhibited severe atrophy of visceral fat and progression of severe hypertension. The expression and release of leptin and adiponectin were impaired at 6 and 20 weeks of age. Candesartan suppressed the development of lipoatrophy and reduced the incidence of stroke at 20 weeks of age. Candesartan also enhanced the expression of adiponectin and leptin by inducing the overexpression of peroxisome proliferator activated receptor γ. Circulating level of leptin was significantly higher in candesartan group than in the control group, whereas adiponectin was similar in both groups. Intravenous administration of adiponectin resulted in enhancement of adiponectin expression in adipose tissue, but no remarkable effects were found in pathophysiology in SHRSP.ConclusionsOur results indicate that candesartan protects against hypertension and adipocyte dysfunction in SHRSP. The induction of leptin expression appeared to be important factor in the inhibition of stroke lesions, whereas adiponectin was not a major regulator of blood pressure in SHRSP with genetic hypertension. Further studies are needed to elucidate the role of the renin–angiotensin system in adipose tissue dysfunction in relation to hypertensive end-organ damage.

Regulation of adiponectin secretion and expression by insulin and β‐agonists in rat

AbstractThe adipocytokines, including adiponectin, are important factors in the regulation of insulin sensitivity and carbohydrate and lipid metabolism. It is proved that concentrations of adiponectin are decreased in obesity, an insulin resistant state. The current study is to address potential mechanisms regulating adiponectin secretion and expression in vivo. To observe the regulation of adiponectin by fasting‐refeeding and β‐agonists, male Wistar rats were fasted for 18 h and allowed to refeed with/without a β3‐adrenergic receptor agonist infused into refeeding rats. We also investigated the effects of insulin clamp on adiponectin secretion and expression, including euglycemic–hyperinsulinemic clamp and hyperglycemic–hyperinsulinemic clamp. Plasma adiponectin levels were determined by radioimmunoassay. Using real‐time PCR assays, we analyzed the expression of adiponectin genes in rat primary adipocytes. Refeeding of 18‐h fasted rats increased plasma adiponectin concentration (∼2‐fold) and adipose tissue adiponectin expression (∼3‐fold), and these effects were mimicked by hyperinsulinemia in the absence of refeeding and completely blocked by administration of β‐agonists during refeeding. We conclude that (i) adiponectin secretion and expression are acutely regulated in vivo by nutritional status; (ii) in vivo, insulin and β‐agonists act directly at the adipocyte to regulate adiponectin secretion and expression.

Correlation between severity of coronary artery atherosclerosis and epicardial adipose tissue adiponectin expression in patients with coronary artery disease

Objective To investigate the correlation between epicardial adipose tissue adiponectin expression in patients with coronary artery disease (CAD) and severity of coronary artery atherosclerosis.Methods Choose 52 cases in coronary artery disease group and valvular disease group of 54,took peripheral venous blood and epicardial adipose tissue.paitents were devied into three groups according to Gensini' s score.Adiponectin was measured with the use of enzyme linked immunosorbent assay ( ELISA ),reverse transcription-polymerase chain reaction (RT-PCR) was used to analysis adiponectin mRNA,Western blotting method was used to detect adiponectin protein expression.Results Serum adiponectin were valvular disease group ( 14.1 ± 4.2) mg/L,coronary heart disease group ( 9.3 ± 4.5 ) mg/L ( P ＜ 0.01 ).serum adiponectin of the three groups were ( 10.9 ± 5.5 ) mg/L ( n =16 ),( 8.4 ± 4.2 ) mg/L ( n =20 ),(6.2 ± 5.3 ) mg/L( n =18 ) ( P ＜ 0.05 ) ; RT-PCR and Western blotting analysis of adiponectin levels in epicardial adipose tissue showed a downward trend with increased Gensini' s score.Conclusion Epicardial adipose tissue levels of adiponectin was dreased in patient with CAD,low Epicardial adipose tissue levels of adiponectinwas related to the severity of coronary artery atherosclerosis. Key words: Coronary artery disease; Adiponectin; Epicardial adipose tissue

Adipose Tissue Inflammation and Adiponectin Resistance in Patients With Advanced Heart Failure

Background— Heart failure (HF) is characterized by inflammation, insulin resistance, and progressive catabolism. We hypothesized that patients with advanced HF also develop adipose tissue inflammation associated with impaired adipokine signaling and that hemodynamic correction through implantation of ventricular assist devices (VADs) would reverse adipocyte activation and correct adipokine signaling in advanced HF. Methods and Results— Circulating insulin, adiponectin, leptin, and resistin levels were measured in 36 patients with advanced HF before and after VAD implantation and 10 healthy control subjects. Serum adiponectin was higher in HF patients before VAD implantation compared with control subjects (13.3±4.9 versus 6.4±2.1 μg/mL, P =0.02). VAD implantation (mean, 129±99 days) reduced serum adiponectin (7.4±3.4 μg/mL, P <0.05) and improved insulin resistance (Homeostasis Assessment Model of insulin resistance: 6.3±5.8–3.6±2.9; P <0.05). Adiponectin expression in adipose tissue decreased after VAD implantation (−65%; P <0.03). Adiponectin receptor expression was suppressed in the failing myocardium compared with control subjects and increased after mechanical unloading. Histomorphometric analysis of adipose tissue specimens revealed reduced adipocyte size in patients with advanced HF compared with control subjects (1999±24 μm 2 versus 5583±142 μm 2 in control subjects; P <0.05), which increased after VAD placement. Of note, macrophage infiltration in adipose tissue was higher in advanced HF patients compared with control subjects (+25%; P <0.01), which normalized after VAD implantation. Conclusions— Adipose tissue inflammation and adiponectin resistance develop in advanced HF. Mechanical unloading of the failing myocardium reverses adipose tissue macrophage infiltration, inflammation, and adiponectin resistance in patients with advanced HF.

Regulation of adiponectin secretion by soy isoflavones has implication for endocrine function of the testis

Testicular Leydig cells are the predominant source of the male sex steroid hormone testosterone (T), which is required to maintain male fertility. There is now growing evidence that environmental stressors, including chemicals present in food, air and water, may affect energy balance. A relationship between energy balance and reproductive capacity has been proposed for a long time. In the present study, developmental exposures of male rats to soy isoflavones in the maternal diet from gestational day 12 to day 21 post-partum enhanced adiponectin expression in adipose tissue and increased serum adiponectin concentrations in adulthood. However, exposure to soy isoflavones caused a decrease in T production and expression of adiponectin and its receptor (adipoR2) in Leydig cells. In separate experiments, incubation of Leydig cells with recombinant adiponectin in the absence of isoflavones caused a decrease in T biosynthesis associated with diminished expression of the cholesterol transporter steroidogenic acute regulatory protein (StAR). Thus, chemical-induced alterations in serum adiponectin concentrations have implication for steroid hormone secretion. The results also imply that changes in adipose tissue metabolism occasioned by exposure to dietary estrogens, and perhaps other estrogenic agents, possibly contribute to deficiencies in reproductive capacity attributed to these compounds.

Adiponectin expression and metabolic markers in obesity and Type 2 diabetes

Adiponectin has emerged over the last decade as a key adipokine linking obesity, insulin resistance, and Type 2 diabetes. However, the molecular mechanisms controlling adiponectin expression in adipose tissue are not fully elucidated. Furthermore, increasing evidence indicates that peroxisome proliferator-activated receptor- γ (PPAR-γ) plays an important, and beneficial, role in modulating adiponectin expression. The aim of the present study was to assess the separate role of obesity and Type 2 diabetes in the relationship between endogenous PPAR-γ signaling and adiponectin expression in subcutaneous adipose tissue. Enzyme-linked immuno sor bent assay and real time quantitative PCR analysis were carried out in overweight, obese, and/or diabetic Tunisian patients who underwent an abdominal surgery. These results collectively indicate that circulating levels of adiponectin were decreased in all overweight, obese, and/or diabetic (p<0.001). However, the subcutaneous mRNA expression of adiponectin was reduced only in diabetics (p<0.01) but presents some discrepancies in obese individuals. Moreover, mRNA levels of adiponectin were positively correlated with levels of mRNA encoding PPARγ and its heterodimeric partner retinoid X receptor-α (RXR-α), in both obese and diabetic patients. Our study on Tunisian patients shows impaired regulation of circulating and mRNA adiponectin levels dependent of metabolic disorders in obesity and Type 2 diabetes. The data suggest that subcutaneous adipose tissue may play an important role in modulating adiponectin expression in diabetes and obesity. Moreover, adiponectin mRNA could be potentially regulated by endogenous PPARγ/RXRα-dependent pathways.