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PubMed2005

The influence of adiponectin gene polymorphism on the rosiglitazone response in patients with type 2 diabetes.

OBJECTIVE: The aim of this study was to examine the effects of rosiglitazone on adiponectin and plasma glucose levels in relation with common adiponectin gene (ACDC) polymorphisms. RESEARCH DESIGN AND METHODS: A total of 166 patients with type 2 diabetes were treated with rosiglitazone (4 mg/day) for 12 weeks without changing any of their previous medications. In all, single nucleotide polymorphism (SNP)45 and SNP276 of ACDC were examined. RESULTS: Regarding SNP45, there was a smaller reduction in the fasting plasma glucose (FPG) level and the HbA(1c) value in the carriers of the GG genotype than in the carriers of the other genotypes (P = 0.031 and 0.013, respectively). There was a smaller increase in the serum adiponectin concentration for the GG genotype than for the other genotypes (P = 0.003). Regarding SNP276, there was less reduction in the FPG level for the GG genotype than for the other genotypes (P = 0.001). In the haplotype analysis, the reductions in the FPG and HbA(1c) levels were smaller for the GG homozygote haplotype than for the other haplotypes (P = 0.001 and 0.001, respectively). The increase in the plasma adiponectin concentration for the GG homozygote haplotype was smaller than that of the other haplotypes (P = 0.003). CONCLUSIONS: These data suggest that genetic variations in the adiponectin gene can affect the rosiglitazone treatment response of the circulating adiponectin level and blood glucose control in type 2 diabetic patients.

Adiponectin↗
PubMed2005

Is adiponectin level a predictor of nonalcoholic fatty liver disease in nondiabetic male patients?

AIM: Adiponectin is a hepatic insulin sensitizer and also an inhibitor of tumor necrosis factor. We studied its levels in nondiabetic patients with nonalcoholic fatty liver disease (NAFLD) and compared with control group. METHODS: Thirty-five patients who had elevated serum aminotransferase levels with bright liver and 34 healthy volunteers without liver disease were evaluated. Age, gender and body mass index (BMI) were recorded. Fasting plasma glucose, insulin, adiponectin, proinsulin and lipid profile were measured. A standard oral glucose tolerance test (OGTT) with insulin response was performed and the index of insulin resistance was calculated according to the homeostasis model assessment (HOMA) method. RESULTS: According to the OGTT results, none of the participants had diabetes. Serum adiponectin levels were statistically significantly lower in patients with NAFLD than in control group (8.14+/-3.4 microg/mL vs 12.4+/-9.4 microg/mL, respectively, P<0.01). A statistically significant correlation was found between adiponectin and BMI (r : -0.33, P<0.01), HOMA (r : -0.26, P<0.05), proinsulin (r : -0.32, P<0.01), AST (r : -0.25, P<0.05), ALT (r : -0.26, P<0.05) or GGT (r : -0.22, P<0.05). In multiple regression analysis models, adiponectin levels were the only predictor of NAFLD in males, whereas in female group it was the BMI. CONCLUSION: Low adiponectin level might be a predictor of NAFLD especially in male nondiabetics.

Adiponectin↗
PubMed2006

Roles of adipocyte derived hormone adiponectin and resistin in insulin resistance of type 2 diabetes.

AIM: To detect plasma levels of new adipocyte derived hormone adiponectin and resistin in type 2 diabetes patients and to explore their potential roles in insulin resistance in type 2 diabetes. METHODS: According to the body mass index (BMI), 60 type 2 diabetes patients were divided into two groups, one group was non-obese diabetes patients with BMI<25Kg/M(2) (30 cases) and the other group was obese diabetes patients with BMI>25Kg/M(2) (30 cases). There were 28 healthy persons in the control group. ELISA technique was employed to determine the plasma adiponectin and resistin concentrations. The fasting blood glucose, insulin and blood lipid were detected respectively by electrocheminescence immunoassay and immunoturbidimetric assay. Insulin resistance index and insulin sensitive index were calculated by the homeostasis model assessment (HOMO). RESULTS: The levels of plasma adiponectin were decreased significantly in diabetes group compared to that in control group (non-obese: 8.58+/-0.86, obese: 6.22+/-1.34 vs 10.53+/-1.47 P<0.05); moreover, adiponectin concentration in obese diabetes group was significantly decreased compared to that in non-obese diabetes group (6.22+/-1.34 vs 8.58+/-0.86, P<0.05). The levels of plasma resistin were increased significantly in diabetes group compared to that in control group (obese: 18.64+/-4.65, non-obese: 24.05+/-9.07 vs 14.16+/-5.25, P<0.05, P<0.05); furthermore, the levels of resistin in obese diabetes group were increased significantly compared to that in non-obese diabetes group (P<0.05). Plasma adiponectin was correlated negatively with BMI, blood glucose, insulin resistance index and triglyceride (respectively, r=-0.55, P<0.01; r=-0.51, P<0.05; r=-0.52, P<0.05ûr=-0.39, P<0.05), while it was positively correlated with insulin sensitive index (r=0.45, P<0.05). Conversely, plasma resistin correlated positively with BMI, blood glucose, triglyceride and insulin resistance index (respectively, r=0.40, P<0.05; r=0.52, P<0.05; r=0.46, P<0.01; r=0.27, P<0.05), and negatively correlated with insulin sensitive index (r=-0.32, P<0.05). CONCLUSION: Plasma adiponectin and resistin are associated with the disorder of metabolism of glucose and lipid in diabetes. The relationship between these hormone and insulin sensitivity suggests that they may take part in the development of insulin resistance of type 2 diabetes.

Adiponectin↗
PubMed2003

Adiponectin and resistin--new hormones of white adipose tissue.

Adiponectin and resistin are recently described secretory products of adipose tissue. Adiponectin is secreted by fat cells and circulates in the blood. Plasma adiponectin concentration is reduced in obese animals and humans and in patients with type 2 diabetes mellitus. Adiponectin stimulates fatty acids oxidation, decreases plasma triglycerides, and improves glucose metabolism by increasing insulin sensitivity. In addition, adiponectin inhibits the inflammatory process and possibly atherogenesis by suppressing the migration of monocytes/macrophages and their transformation into foam cells. Plasma adiponectin is lower in patients with ischemic heart disease than in body mass index-matched healthy individuals. Hypoadiponectinemia may contribute to insulin resistance and accelerated atherogenesis associated with obesity. Resistin/FIZZ3 is a member of the newly discovered cysteine-reach secretory protein family, referred to as 'resistin-like molecules' (RELM) or 'found in inflammatory zone' (FIZZ), together with FIZZ1/RELMalpha and FIZZ2/RELMbeta. Each of these has unique tissue distribution. Both resistin and FIZZ1/RELMalpha are expressed in adipose tissue. Initial studies in rodents suggested that resistin is upregulated in obesity and may be involved in the development of insulin resistance. Later studies failed to confirm this hypothesis and demonstrated reduced resistin expression in adipose tissue of obese animals. In human adipose tissue resistin is detectable at a very low level, and there is no relationship between resistin expression and obesity. Although the role of resistin in linking human obesity with type 2 diabetes is thus questionable, this protein is detected in peripheral blood monocytes,

Adiponectin↗
PubMed2003

Cloning and expression of adiponectin and its globular domain, and measurement of the biological activity in vivo.

3T3-L1-adipocytes produce the adipocyte complement related protein of 30 kD (ACRP30), which is exclusively expressed in differentiated adipocytes. Decreased expression of ACRP30 correlates with insulin resistance in mouse models of altered insulin sensitivity. Adiponectin, the human homologue of ACRP30, circulates in human plasma at high levels. Plasma adiponectin levels have been reported to be decreased in some insulin-resistant states, such as obesity and type II diabetes mellitus. Here, full-length adiponectin and its C-terminal globular head domain (gAdiponectin) were expressed in Escherichia coli and gAdiponectin was used to immunize a rabbit to obtain polyclonal antiserum with titer of 10,000. Adiponectin was detected in human plasma with the use of gAdiponectin anti-serum by Western blot analysis, which was also detected by gACRP30 anti-serum. Injection in alloxan-treated rats with purified recombinant fusion adiponectin or gAdiponectin transiently abolished hyperglycemia. So adiponectin and gAdiponectin might have activity as a glucose lowering agent and potentially as a therapeutic for metabolic disease. All these results suggested that the recombinant protein had biological activity, and provided a useful tool in further studies.

3T3-L1 Cells↗
PubMed2003

[Adiponectin: a new adipocytokine].

Adipose tissue is not simply a store of excess energy, but also secretes a variety of proteins into circulating blood that influence systemic metabolism. These include tumor necrosis factor (TNF-alpha), plasminogen activator inhibitor type 1 (PAI-1), leptin, resistine and adiponectin. These are collectively known as adipocytokines. Adiponectin (also referred to as AdipoQ, Acrp 30, apM1 or GBP28) is a novel adipose-specific protein. A recent genome study mapped a susceptibility locus for type 2 diabetes and the metabolic syndrome on chromosome 3q27, where the adiponectin gene is located. Adiponectin is a peculiar adipocytokine because in contrast to the markedly increased levels of many others, as leptin or TNF-alpha, its level is reduced in obesity and type 2 diabetes. The administration of thiazolidinediones, which are synthetic PPARs-gamma ligands, significantly increases the plasma adiponectin concentrations, an effect that could improve insulin sensitivity. Thus, the administration of adiponectin may provide a novel treatment modality for insulin resistance and type 2 diabetes.

Adiponectin↗
PubMed2004

Serum adiponectin level in patients with obstructive sleep apnea hypopnea syndrome.

BACKGROUND: Adiponectin, secreted by adipocytes, has been found to be associated with diabetes, obesity and some cardiovascular diseases. Obstructive sleep apnea hypopnea syndrome (OSAHS) is also closely related to obesity and easily complicated with diabetes and some cardiovascular diseases. This study was carried out to explore the change of serum adiponectin level in patients with OSAHS. METHODS: Polysomnography was performed in 71 patients with OSAHS (OSAHS group) and 26 simple obese controls (control group). The two groups had no significant difference in age and body mass index (BMI). Radioimmunoassy was used to test serum adiponectin level. RESULTS: Serum adiponectin level was significantly lower in OSAHS group [(5.03 +/- 1.01) mg/L] than that in the control group [(7.09 +/- 1.29) mg/L, P < 0.05]. The differences between two groups were independent of gender. In OSAHS groups, serum adiponectin levels were negatively correlated with apnea hypopnea index (AHI) (r = -0.78, P < 0.01), BMI (r = -0.13, P < 0.05), waist circumference (r = -0.36, P < 0.01), and neck circumference (r = -0.42, P < 0.01), but positively correlated with the minimal pulse oxyhemoglobin saturation (r = 0.48, P < 0.01). CONCLUSION: OSAHS may contribute to the decrease of serum adiponectin level independent of obesity.

Adiponectin↗
PubMed2004

[Adiponectin gene polymorphism and protein dysfunction in the development of insulin resistance].

Adiponectin, an adipocyte-secreted protein encoded by the ACDC gene (also known as APM1), has been shown to play an important role in the regulation of fatty acid and glucose metabolism in liver and muscle, where it modulates insulin sensitivity. Adiponectin enhances fatty acid oxidation in liver and muscle, thus reducing triglyceride content in these tissues. Moreover, it stimulates glucose utilization in muscle and inhibits glucose production by the liver, consequently decreasing blood glucose levels. Plasma adiponectin levels are positively correlated with insulin sensitivity in humans. Circulating adiponectin forms a wide range of multimers. Mutations in the ACDC gene result in an impaired multimerization and/or impaired secretion of adiponectin from adipocytes, both linked to the development of insulin resistance and type II diabetes. This review focuses on the molecular mechanisms underlying hypoadiponectinemia associated with the diabetic phenotype. We further discuss the more recent findings that implicate adiponectin multimer formation as an important feature of the biological function of this adipocyte-derived hormone.

Adiponectin↗
PubMed2006

[Effects of soy isoflavone on gene expression of adiponectin in insulin-resistance rats induced by high-fat and high-sugar diet].

OBJECTIVE: To study the effects and mechanisms of soy isoflavone (SIF) on improving insulin resistance (IR) status in IR rats induced by high-fat and high-sugar diet. METHODS: IR rats induced by high-fat and high-sugar diet were assigned into four groups and gavaged with SIF at doses of 0 (model control group), 50, 150 and 450 mg/kg bw for 4 weeks, respectively. Insulin, glucose, adiponectin in serum and adiponectin mRNA in perirened adipocyte were detected. RESULTS: Compared with model control group, body weight and fat pad weight were lower, and serum adiponectin and adiponectin mRNA expression were higher in the 450 mg/kg bw group, insulin and insulin-resistance index were lower in the 150 mg/kg bw group and 450 mg/kg bw. There is no differences in plasma glucose levels among groups. There is an negative correlation between insulin-resistance index and serum adiponectin level (Y = 24.802 - 2.856X, r = - 0.881, n = 47, P < 0.01). CONCLUSION: These results suggest that soy isoflavone may decrease adipose deposition, increase serum adiponectin level, and ameliorate insulin sensitivity.

Adiponectin↗
PubMed2006

[Metformin hydrochloride ameliorates adiponectin levels and insulin sensitivity in adolescents with metabolic syndrome].

OBJECTIVES: Metabolic syndrome (MS) in adolescents was reported to be closely associated with cardiovascular diseases in adulthood. However, no unified treatment measure for MS in adolescents is currently available. The aim of this study was to measure the changes of serum adiponectin levels, insulin sensitivity and other biochemical markers after metformin therapy in adolescents with MS, which might provide some information for set up a unified therapeutic measure for MS in adolescents. METHODS: In this study, 348 moderately or severely obese adolescents and 24 non-obese healthy adolescents matched in age and sex were enrolled. The obese group included 208 males and 140 females aged from 7 to 16 years (11.5 +/- 2.1 years). Oral glucose tolerance test and biochemical markers measurement were done to all these subjects. Whole body insulin sensitivity index (WBISI), homeostasis model assessment-insulin resistance (HOMA-IR) and fasting serum adiponectin were compared among 36 adolescents with MS (who had two or three abnormalities of hyperglycosemia, hypertension or dyslipidemia), 61 simple obese subjects without abnormality of biochemical markers and 24 healthy controls. Moreover, the changes of WBISI, HOMA-IR and adiponectin levels in 20 cases with MS after metformin therapy for 3 months were measured. RESULTS: (1) HOMA-IR in control group (1.3), simple obese group (2.3) and MS group (4.9) increased by turns (F = 54.08, P < 0.001). WBISI and serum adiponectin in control group, simple obese group and MS group decreased by turns with significant difference [89.6, 22.8 and 10.7, F = 30.06; (7.1 +/- 2.6), (5.9 +/- 1.9), (2.8 +/- 0.9) mg/L, F = 64.93; P < 0.01 for all]. (2) HOMA-IR after metformin therapy decreased [5.7 (1.9-12.4) vs. 2.9 (0.9-7.4), t = 5.05, P < 0.01]; while the serum adiponectin levels increased with significant differences [(3.0 +/- 0.9) mg/L vs. (6.1 +/- 1.9) mg/L, t = 6.19, P < 0.01]. Systolic blood pressure [(132.4 +/- 7.5) mm Hg vs. (116.6 +/- 9.1) mm Hg, t = 8.36, P < 0.01], 2-hour glucose [(8.2 +/- 2.9) mmol/L vs. (5.3 +/- 1.0) mmol/L, t = 3.96, P < 0.01], triglyceride [(2.8 +/- 1.2) mmol/L vs. (1.3 +/- 0.9) mmol/L, t = 4.22, P < 0.01], total cholesterol [(4.9 +/- 0.6) mmol/L vs. (4.0 +/- 0.6) mmol/L, t = 4.72, P < 0.01], alanine aminotransferase [80.5 (29.0-286.0) U/L vs. 56.0 (23.0-163.0) U/L, t = 3.80, P < 0.01]. CONCLUSION: Insulin sensitivity in adolescents with MS was lower than that of simple obese group. Metformin can improve or ameliorate adiponectin levels, insulin sensitivity and some clinical markers.

Adiponectin↗
PubMed2006

[Effects of globular adiponectin, glucose and free fatty acid on AMPK and ACC phosphorylation in INS-1 beta cells].

OBJECTIVE: To investigate effects of glucose and free fatty acid at different concentrations on phosphorylation of adenosine-5'-monophosphate activated protein kinase(AMPK) and acetyl CoA carboxylase (ACC) in INS-1 cells, and effects of globular adiponectin on phosphorylation of AMPK and ACC. METHODS: INS-1 cells were cultured and treated with 5 mmol/L glucose or 0.25 mmol/L free fatty acids, and time courses and dose responses of different dosages of glucose and fatty acid on phosphorylation of AMPK and ACC were measured. We measured the effects of the pharmacological AMPK activator AICAR (5-aminoimidazole-4-carboxamide-riboside) and globular adiponectin on phosphorylation of AMPK and ACC. RESULTS: Glucose and fatty acid at different concentrations inhibited the phosphorylation of AMPK and ACC at the end of 60 min, but AICAR increased the phosphorylation of AMPK and ACC significantly, while 2.5 mg/L globular adiponectin increased the phosphorylation of AMPK and ACC by 23% (P<0.05) and 50% (P<0.05) respectively, at baseline. In the presence of 5 mmol/L glucose, globular adiponectin increased AMPK and ACC phosphorylation by 1.4-fold (P<0.05) and 3-fold (P<0.01), respectively. In the presence of 0.25 mmol/L free fatty acid, globular adiponectin increased AMPK and ACC phosphorylation 3-fold (P<0.05) and 5-fold (P<0.01) respectively. CONCLUSION: In cultured islet cells, glucose and free fatty acid at various concentrations inhibit the phosphorylation of AMPK and ACC, but AICAR and globular adiponectin 2.5 mg/L increase the phosphorylation level. This may constitute a mechanism to increase fatty acid oxidation and decrease triglyceride accumulation in islet beta-cells.

AMP-Activated Protein Kinases↗
PubMed2004

Antiretroviral drugs with adverse effects on adipocyte lipid metabolism and survival alter the expression and secretion of proinflammatory cytokines and adiponectin in vitro.

OBJECTIVE: The lipodystrophy syndrome is a major adverse effect of highly active antiretroviral therapy (HAART), associated with altered circulating levels and adipose tissue mRNA expression of proinflammatory cytokines interleukin-6 (IL-6) and tumour necrosis factor (TNF)alpha, and adiponectin. Proinflammatory cytokines and adiponectin, which are secreted by adipose tissue, regulate fat metabolism, insulin sensitivity and adipose cell apoptosis. We examined the direct effects of individual antiretrovirals on lipid metabolism and cytokine and adiponectin production by cultured adipocytes. METHODS: Differentiating 3T3-F442A cells and differentiated 3T3-L1 adipocytes were treated for 12 or 4 days, respectively, with protease inhibitors (PIs) indinavir, nelfinavir, amprenavir, lopinavir and ritonavir, or nucleoside reverse transcriptase inhibitors (NRTIs) stavudine and zidovudine, at near-Cmax concentrations. Lipid metabolism was estimated by Oil Red O staining of intracellular lipids, mRNA expression of fatty acid synthase and adipocyte lipid binding protein 2, and insulin activation of lipogenesis. Apoptosis was estimated by flow cytometry. The expression and secretion of proinflammatory cytokines (IL-6, TNFalpha and IL-1beta) and adiponectin were evaluated by real-time reverse transcription PCR and ELISA. RESULTS: Chronic treatment of 3T3-F442A differentiating adipocytes and differentiated 3T3-L1 adipocytes with PIs and NRTIs reduced lipid accumulation, mRNA expression of lipid markers and insulin-induced lipogenesis. IL-6, TNFalpha, IL-1beta and adiponectin expression and secretion were markedly altered in differentiating 3T3-F442A adipocytes. PIs had either no effect on differentiated 3T3-L1 adipocytes (TNFalpha expression and sucretion) or their effect was less marked than in 3T3-F442A cells. Indinavir and amprenavir did not alter cytokine secretion and expression by mature adipocytes. The effects of stavudine and zidovudine on differentiating and mature adipocytes were similar, despite the difference in treatment procedure. The drugs with the strongest effect on TNFalpha expression also increased adipocyte apoptosis, in contrast to the drugs that only moderately increased TNFalpha expression. CONCLUSIONS: These results suggest that increased cytokine and decreased adiponectin secretion and expression induced by some PIs and NRTIs may contribute to the adipose tissue loss (via apoptosis and lipid leakage) and insulin resistance associated with the lipodystrophy syndrome.

3T3-L1 Cells↗
PubMed2004

Adiponectin receptors gene expression and insulin sensitivity in non-diabetic Mexican Americans with or without a family history of Type 2 diabetes.

AIMS/HYPOTHESIS: The recent discovery of two adiponectin receptors (AdipoR1 and AdipoR2) will improve our understanding of the molecular mechanisms underlying the insulin-sensitising effect of adiponectin. The aim of this study was to determine for the first time whether skeletal muscle AdipoR1 and/or AdipoR2 gene expression levels are associated with insulin resistance. METHODS: Using RT-PCR and northern analysis we measured AdipoR1 and AdipoR2 gene expression in skeletal muscle from healthy Mexican Americans with normal glucose tolerance who had (n=8) or did not have (n=10) a family history of Type 2 diabetes. RESULTS: Gene expression profiling indicated that the AdipoR1 and AdipoR2 isoforms are highly expressed in human skeletal muscle, unlike in mice where AdipoR2 expression was highest in the liver, and AdipoR1 was highest in skeletal muscle. In the study subjects, the expression levels of AdipoR1 (p=0.004) and AdipoR2 (p=0.04), as well as plasma adiponectin concentration (p=0.03) were lower in people with a family history of Type 2 diabetes than in those with no family history of the disease. Importantly, the expression levels of both receptors correlated positively with insulin sensitivity (r=0.64, p=0.004 and r=0.47, p=0.048 respectively). CONCLUSIONS/INTERPRETATION: Collectively, these data indicate that both isoforms of the adiponectin receptor play a role in the insulin-sensitising effect of adiponectin.

Adiponectin↗
PubMed2006

The regulation of adiponectin receptors in human prostate cancer cell lines.

Obesity is a risk factor for prostate cancer, and plasma levels of the adipokine, adiponectin, are low in the former but high in the latter. Adiponectin has been shown to modulate cell proliferation and apoptosis, suggesting that adiponectin and its receptors (Adipo-R1, Adipo-R2) may provide a molecular association between obesity and prostate carcinogenesis. We show for the first time, the protein distribution of Adipo-R1 and Adipo-R2 in LNCaP and PC3 cells, and in human prostate tissue. Using real-time RT-PCR we provide novel data demonstrating the differential regulation of Adipo-R1 and Adipo-R2 mRNA expression by testosterone, 5-alpha dihydrotestosterone, beta-estradiol, tumour necrosis factor-alpha, leptin, and adiponectin in LNCaP and PC3 cells. Our findings suggest that adiponectin and its receptors may contribute to the molecular association between obesity and prostate cancer through a complex interaction with other hormones and cytokines that also play important roles in the pathophysiology of obesity and prostate cancer.

Adiponectin↗
PubMed2006

Adiponectin protects human neuroblastoma SH-SY5Y cells against acetaldehyde-induced cytotoxicity.

Acetaldehyde, an inhibitor of mitochondrial function, has been widely used as a neurotoxin because it elicits a severe Parkinson's disease-like syndrome with elevation of the intracellular reactive oxygen species (ROS) level and apoptosis. Adiponectin, secreted from adipose tissue, mediates systemic insulin sensitivity with liver and muscle as target organs. In this study, we investigated the protective effects of adiponectin on acetaldehyde-induced apoptosis in human neuroblastoma SH-SY5Y cells and attempted to examine its mechanism. Acetaldehyde-induced apoptosis was moderately reversed by adiponectin treatment. Our results suggest that the protective effects of adiponectin on acetaldehyde-induced apoptosis may be ascribed to ability to induce the expression of anti-oxidant enzymes and to regulate Bcl-2 and Bax expression. These data indicate that adiponectin may provide a useful therapeutic strategy for the prevention of progressive neurodegenerative disease such as Parkinson's disease.

Acetaldehyde↗
PubMed2006

Adiponectin receptors in human adipose tissue: effects of obesity, weight loss, and fat depots.

OBJECTIVE: To investigate the presence and regulatory properties of the adiponectin receptors, AdipoR1 and AdipoR2, in human adipose tissue (AT) and in isolated human adipocytes. RESEARCH METHODS AND PROCEDURES: The effect of obesity, weight loss, and gender on expression of AdipoR1 and AdipoR2 was investigated in subcutaneous AT. The influence of fat distribution on these receptors was investigated in paired samples of subcutaneous and omental AT. Gene expression of these receptors was quantified by reverse transcriptase-polymerase chain reaction. RESULTS: AdipoR1 mRNA levels were approximately 10-fold higher than adipoR2 in both AT fragments and in isolated adipocytes. AdipoR1 expression was lower in AT from obese subjects (p < 0.05) compared with that from normal-weight subjects, and AdipoR1 displayed a negative correlation with BMI (r = -0.53, p < 0.01). In obese subjects, weight loss (approximately 12 kg) increased AdipoR1 expression by 80% in AT (p < 0.01). Concerning regional differences, AdipoR1 showed significantly lower expression in omental AT than in subcutaneous AT (p < 0.01). No gender difference was observed in the expression of these receptors. In human preadipocyte cultures, AdipoR1 expression was not induced during the differentiation process, whereas AdipoR2 was induced by 5-fold (p < 0.05). DISCUSSION: AdipoR1 is highly expressed in human AT, indicating that adiponectin may have biological effects in AT in an autocrine/paracrine manner. AdipoR1 expression in AT is reduced in obese subjects and is increased after weight loss. Thus, it can be suggested that adiponectin might have reduced biological effects in AT due to low levels of adiponectin receptors in obese subjects and in omental adipocytes, which may further aggravate the negative metabolic effect of low levels of adiponectin characterizing the obese state.

Adipocytes↗
PubMed2006

Up-regulation of adiponectin, its isoforms and receptors in end-stage kidney disease.

BACKGROUND: Despite the favourable effects of adiponectin on the vasculature and insulin resistance (IR), levels are increased in patients with end-stage kidney disease (ESKD), in whom both IR and atherosclerosis are prevalent. METHODS: To investigate this paradox, we examined the distribution of adiponectin isoforms, the expression of adiponectin receptor (AdipoR) mRNA on peripheral blood mononuclear cells (PBMC) in 41 patients with ESKD on haemodialysis and 41 matched controls, and its function by adenosine monophosphate-activated protein kinase (AMPK) phosphorylation of AdipoR on PBMC. We also compared the expression of AdipoR on PBMC with that on muscle and subcutaneous and visceral fat in 10 patients undergoing elective cholecystectomy. RESULTS: The proportion of the high molecular weight (HMW) isoform of adiponectin was increased in the dialysis group (P = 0.001), even though these patients were significantly insulin resistant compared with controls (P = 0.006). AdipoR1 and AdipoR2 on PBMC were also increased in patients with ESKD (P < 0.05 and P = 0.007, respectively), but levels did not correlate with IR, the HMW isoform or other anthropometric measurements. There was a strong correlation between AdipoR1 and AdipoR2 on PBMC in ESKD and in subcutaneous and visceral fat in controls. However, there was no relationship between AdipoR in PBMC, muscle or visceral fat. Phosphorylation of AMPK by recombinant adiponectin showed that AdipoR on PBMC, from controls and ESKD patients, were equally functional. CONCLUSIONS: IR in ESKD is not explained by the change in isoformic distribution, or by AdipoR down-regulation or dysfunction. Rather, this receptor-ligand axis is up-regulated and may be a beneficial response to the inflammatory milieu of ESKD.

AMP-Activated Protein Kinases↗
PubMed2005

Impaired activation of AMP-kinase and fatty acid oxidation by globular adiponectin in cultured human skeletal muscle of obese type 2 diabetics.

Adiponectin is an adipocyte-derived hormone associated with antidiabetic actions. In rodent skeletal muscle, globular adiponectin (gAD) activates AMP-kinase (AMPK) and stimulates fatty acid oxidation effects mediated through the adiponectin receptors, AdipoR1 and AdipoR2. In the present study, we examined the mRNA expression of adiponectin receptors and the effects of gAD on AMPK activity and fatty acid oxidation in skeletal muscle myotubes from lean, obese, and obese type 2 diabetic subjects. Myotubes from all groups expressed approximately 4.5-fold more AdipoR1 mRNA than AdipoR2, and obese subjects tended to have higher AdipoR1 expression (P = 0.052). In lean myotubes, gAD activates AMPKalpha1 and -alpha2 by increasing Thr172 phosphorylation, an effect associated with increased acetyl-coenzyme A carboxylase (ACCbeta) Ser221 phosphorylation and enhanced rates of fatty acid oxidation, effects similar to those observed after pharmacological AMPK activation by 5-aminoimidazole-4-carboxamide riboside. In obese myotubes, the activation of AMPK signaling by gAD at low concentrations (0.1 mug/ml) was blunted, but higher concentrations (0.5 mug/ml) stimulated AMPKalpha1 and -alpha2 activities, AMPK and ACCbeta phosphorylation, and fatty acid oxidation. In obese type 2 diabetic myotubes, high concentrations of gAD stimulated AMPKalpha1 activity and AMPK phosphorylation; however, ACCbeta phosphorylation and fatty acid oxidation were unaffected. Reduced activation of AMPK signaling and fatty acid oxidation in obese and obese diabetic myotubes was not associated with reduced protein expression of AMPKalpha and ACCbeta or the expression and activity of the upstream AMPK kinase, LKB1. These data suggest that reduced activation of AMPK by gAD in obese and obese type 2 diabetic subjects is not caused by reduced adiponectin receptor expression but that aspects downstream of the receptor may inhibit AMPK signaling.

Adenylate Kinase↗