Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of HumansWith Type 2 Diabetes

Statnick, Michael A.; Beavers, Lisa S.; Conner, Laura J.; Corominola, Helena; Johnson, Dwayne; Hammond, Craig; Rafaeloff-Phail, Ronit; Seng, Thomas; Suter, Todd M.; Sluka, James P.; Ravussin, Éric; Gadski, Robert A.; José, F.

doi:10.1155/edr.2000.81

Cited by 200 publications

(145 citation statements)

References 16 publications

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“…10,11 However, the data in type 2 diabetic patients are conflicting. 19,34,39,40 Our results, while confirming lower expression and plasma concentrations in association with obesity, do not show an independent effect of hyperglycemia, in agreement with Koistinen et al 40 On the other hand, our diabetic subjects were all severely obese, so that expression and circulating levels may have bottomed out (a 'floor effect'). Therefore, we cannot completely rule out that hyperglycemia in non-obese (or less obese) subjects may be associated with suppressed ApN.…”

Section: Discussionsupporting

confidence: 90%

“…12,13 Plasma ApN levels have been found to be significantly reduced in subjects with obesity, insulin resistance or DM2; [14][15][16][17] the mechanisms of this reduction are incompletely understood. A reduction in adiponectin gene (APM1) expression and secretion in adipose tissue from obese and diabetic subjects has been reported in some, 7,[18][19][20][21][22] but not all studies. 23 Moreover, the role of omental vs subcutaneous adipose tissue (SAT) in ApN release and the relationship between the protein and its receptors in adipose tissue have not been fully investigated.…”

Section: Introductionmentioning

confidence: 99%

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Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state

et al. 2007

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Objective: To investigate whether adiponectin receptor genes (AdipoR1 and AdipoR2) expression in human subcutaneous (SAT) and visceral (VAT) adipose tissue in severely obese patients with or without diabetes is related to adiponectin gene (APM1) expression and in vivo metabolic parameters. Design: Cross-sectional, clinical research study. Subjects: Total RNA was extracted from SAT and VAT tissue obtained during surgery from 13 lean controls, 30 obese diabetic patients, 19 obese glucose-intolerant patients and 54 obese subjects with normal glucose tolerance. Measurements: Tissue expression of APM1, AdipoR1 and AdipoR2, tissue concentration of adiponectin (ApN), and metabolic variables. Results: APM1 expression was higher in SAT than VAT (1.0670.76 vs 0.6970.52, Po0.0001) as was AdipoR1 (1.1770.70 vs 0.6670.38, Po0.0001) and AdipoR2 (7.0276.19 vs 0.7570.64, Po0.0001). In SAT, APM1 and AdipoR1 expression tended to be lower -by 0.3870.22 and 0.3570.22, respectively -and AdipoR2 expression was markedly depressed -by 4.8271.93 -in association with obesity, whereas presence of diabetes had no additional effect. In VAT, APM1 and AdipoR1 expressions were also reduced -by 0.3670.16 and 0.3070.11, respectively -in association with obesity. Within both SAT and VAT, expression levels of APM1, AdipoR1 and AdipoR2 were all positively interrelated. Tissue ApN concentrations in SAT were similar across groups, whereas ApN levels in VAT were substantially lower in association with obesity (by an average of 63712 ng/mg total protein, Po0.0001). In multivariate models adjusting for sex, age and obesity, serum triglyceride concentrations were reciprocally related to APM1 (r ¼ À0.27, Po0.02), AdipoR1 (r ¼ À0.37, Po0.002 and AdipoR2 expression (r ¼ À0.37, Po0.002) in VAT. Likewise, plasma insulin concentrations were inversely related only to APM1 in VAT (r ¼ À0.25, Po0.03). Conclusions: Severe obesity is associated with suppressed expression of both ApN and its receptors in both SAT and VAT, the expression levels in VAT are specifically linked with hyperinsulinemia and dyslipidemia.

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Section: Discussionsupporting

confidence: 90%

Section: Introductionmentioning

confidence: 99%

Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state

et al. 2007

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“…30 In obese type 2 diabetic subjects, both visceral and subcutaneous APM1 mRNA levels have been reported to be reduced. 31 Taken together, results suggest that there is no difference in APM1 mRNA expression between subcutaneous and visceral adipose tissue in obese subjects, possibly due to the reduction of subcutaneous and perhaps also visceral APM1 mRNA levels, that accompany the obese state.…”

Section: Discussionmentioning

confidence: 73%

“…Males [4] 139.578.2 Females [26] 115.2711.1 Fat % [31] 60.079.1 HOMA index [23] 4.074.2 Fasting glucose (mmol/l) [32] 4.970.6 Fasting insulin (mU/l) [24] 19.5716.8 Leptin (mg/l)…”

Section: Discussionmentioning

confidence: 99%

A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects

et al. 2005

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Objective: Reduced serum adiponectin levels have been found in obesity and type 2 diabetes and variations in the adiponectin gene (APM1) have been associated with type 2 diabetes and features of the metabolic syndrome in different populations. Study Design: Here, we investigated the expression of APM1 in adipose tissue and studied the relationship between variation in APM1 expression, the APM1 G276T polymorphism, the common PPARG Pro12Ala polymorphism and clinical features of 36 morbidly obese (body mass index (BMI) 41.574.9 kg/m 2 ) nondiabetic subjects. Results: APM1 mRNA expression in visceral fat was correlated with serum adiponectin levels (r ¼ 0.54, P ¼ 0.012). In visceral, but not in subcutaneous, adipose tissue APM1 mRNA level was 38% higher among carriers of the APM1 G276T T allele

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“…There is also a negative correlation with the occurrence of Type II (non-insulin-dependent) diabetes mellitus [10,11,12,13]. Moreover, patients with Type II diabetes and coronary heart disease have lower apM-1 plasma concentrations than diabetic patients without coronary heart disease [11].…”

mentioning

confidence: 99%

Identification of regulatory elements in the human adipose most abundant gene transcript-1 (apM-1) promoter: role of SP1/SP3 and TNF-? as regulatory pathways

et al. 2003

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Aims/hypothesis. The human adipocyte-specific apM-1 (adipose most abundant gene transcript-1) gene encodes for a secretory protein of the adipose tissue that seems to play a role in the pathogenesis of obesityrelated insulin resistance and its expression is inhibited by TNF-α. Our aim was to characterize the tissuespecific regulation of the recently cloned apM-1 promoter and the mechanisms of TNF-α-induced downregulation of the apM-1 gene. Methods. We characterised the apM-1 gene by electrophoretic mobility shift assays (EMSA) and luciferase reporter gene assays (LRA). Results. Although several putative binding sites for transcription factors known to be involved in adipogenesis such as C/EBP and PPARγ are present in the promoter, we could not detect any binding of these nuclear proteins from differentiated adipocytes. However, a proximal SP1 binding site specifically binds both, recombinant SP1 protein and SP1 derived from adipocyte nuclear extracts. Since the expression of SP1 during adipocyte differentiation has not yet been analysed, we could show by using EMSA, that binding activity of SP1 is increased during adipocyte differentiation. The stimulatory activity of SP1 was confirmed in LRA by cotransfection experiments in S2 Schneider cells lacking endogenous SP factors. An inhibitory activity of SP3 on the stimulatory effect of SP1 could be confirmed in LRA by contransfection experiments in adipocytes. Nuclear extracts from adipocytes incubated with TNF-α showed a reduced binding activity of SP1. Conclusion/interpretation. SP1 is expressed and its binding activity is enhanced during adipocyte differentiation. SP1 has stimulatory effects, SP3 has inhibitory effects on apM-1 promoter activity, mediated by a proximal SP1 binding site. The mechanism of TNF-α-induced inhibition of apM-1 gene expression is, at least in part, due to a decrease of transcriptional SP1 binding activity caused by TNF-α and thus provides a new mechanism of TNF-α-dependent signalling. [Diabetologia (2002[Diabetologia ( ) 45:1425[Diabetologia ( -1433 Keywords apM-1, adipocyte, promoter, SP1, SP3, TNF-α, transcription, differentiation, diabetes, obesity. The adipose tissue has been considered as a special type of connective tissue, that stores energy in the form of triglycerides and releases energy in the form of non-esterified fatty acids whenever needed. However, increasing evidence suggests that the adipose tissue produces and secretes several highly active molecules. During the last 5 years it has become widely accepted that adipocytes do function as endocrine cells by secreting a variety of highly active molecules. These so-called adipocytokines [1] are secreted from the adipose tissue into the blood stream.

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Decreased Expression Of apM1 in Omental and Subcutaneous Adipose Tissue of HumansWith Type 2 Diabetes

Cited by 200 publications

References 16 publications

Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state

Pattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic state

A polymorphism in the adiponectin gene influences adiponectin expression levels in visceral fat in obese subjects

Identification of regulatory elements in the human adipose most abundant gene transcript-1 (apM-1) promoter: role of SP1/SP3 and TNF-? as regulatory pathways

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