Original Article

Obesity Research (2005) 13, 662669; doi: 10.1038/oby.2005.74

Regulation of Adiponectin Expression in Human Adipocytes: Effects of Adiposity, Glucocorticoids, and Tumor Necrosis Factor **
Mikako Degawa-Yamauchi*, Katherine A. Moss*, Jason E. Bovenkerk*, Sudha S. Shankar*, Charles L. Morrison, Christopher J. Lelliott, Antonio Vidal-Puig, RoseMarie Jones and Robert V. Considine* 1. Division of Endocrinology and Metabolism, Department of Medicine, Indiana University School of Medicine; Indianapolis, Indiana 2. Department of Surgery, Indiana University School of Medicine; Indianapolis, Indiana 3. St. Vincent Bariatric Services, Carmel, Indiana 4. Department of Clinical Biochemistry, Addenbrook's Hospital, Cambridge, United Kingdom Correspondence: Robert V. Considine, Indiana University School of Medicine, 541 North Clinical Drive, Clinical Building 455, Indianapolis, IN 46202-5111. E-mail: rconsidi@iupui.edu
** *

The costs of publication of this article were defrayed, in part, by the payment of page charges. This article must, therefore, be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact. Received 9 July 2004; Accepted 14 January 2005. Top of page

Abstract
Objective: Adiponectin mRNA expression in isolated subcutaneous and omental adipocytes was examined across a wide range of adiposity to determine whether adiponectin synthesis is impaired in these adipose tissue depots in obese humans. Tumor necrosis factor (TNF) and dexamethasone were tested for inhibitory effects on adiponectin release from human adipocytes in vitro. Research Methods and Procedures: Adipocytes were isolated by collagenase digestion of abdominal adipose tissue obtained from subjects undergoing surgical procedures or outpatient needle biopsy. Adiponectin and leptin mRNA were quantitated by real-time reverse

transcriptase-polymerase chain reaction. Adiponectin and leptin secretion from isolated adipocytes treated with dexamethasone or TNF were determined by radioimmunoassay. Results: There was a significant negative correlation between adiponectin gene expression and BMI in subcutaneous adipocytes from 32 women (r = 0.420; p = 0.02). Adiponectin mRNA was also significantly correlated with serum adiponectin (r = 0.44; p = 0.03; n = 25). There was no correlation between adiponectin mRNA expression and BMI in omental adipocytes from 29 women. Leptin mRNA was significantly and positively correlated (r = 0.484; p = 0.01) with BMI in the same omental adipocyte mRNA preparations. In subcutaneous adipocytes from lean subjects, TNF inhibited adiponectin release by 7.4 1.2% (n = 9, p < 0.05) but had no effect on adiponectin release from subcutaneous or omental adipocytes from obese subjects. Dexamethasone significantly inhibited adiponectin release with 24 hours of treatment. Discussion: The data suggest that reduced adiponectin synthesis in subcutaneous adipocytes contributes to lower serum adiponectin levels in obesity and that glucocorticoids regulate adiponectin gene expression in human adipocytes. TNF does not seem to directly inhibit adiponectin synthesis in human adipocytes. Keywords: adiponectin, tumor necrosis factor , human adipocytes Top of page

Introduction
Adipose tissue is an endocrine organ producing many hormones and cytokines (1,2,3,4). The serum concentration of adipose tissue secretory products is generally increased in obese humans because of the combination of a greater number of adipocytes and, for some factors such as leptin, increased secretion from the larger adipocytes present in obese individuals (5). Elevated serum levels of adipose tissue secretory products have been linked to the development of insulin resistance, diabetes, and cardiovascular disease. In contrast, serum levels of the adipose tissue hormone adiponectin are significantly reduced in obese adults (6,7,8) and children (9,10), and this reduction seems to be linked to subsequent development of insulin resistance and diabetes (11,12). Adiponectin is a collagen-like molecule (13,14,15), and observations in rodents and cultured cell models show that this novel protein has antiinflammatory, antiatherogenic, and insulinsensitizing properties. Adiponectin suppresses tumor necrosis factor (TNF) 1 production from cultured macrophages (16) and inhibits TNF -induced monocyte attachment to endothelial cells through a reduction in adhesion molecule expression (17). Adiponectin blocks the binding of oxidized low-density lipoproteins to macrophages and reduces their cholesterol content (18). Adiponectin inhibits growth factorinduced proliferation of smooth muscle cells (19) and protects against intimal thickening in injured vessels (20). Administration of physiological concentrations of adiponectin to lipoatrophic mice lacking the hormone reduces liver and muscle triglyceride content and reverses insulin resistance (21). The hormone also improved insulin

sensitivity in genetically obese and diet-induced obese mice (21). The globular domain of adiponectin induced weight loss in mice through increased fatty acid oxidation (22) and has also been shown to increase glucose uptake in isolated rat adipocytes (23). It can thus be concluded from animal and in vitro work that the lower adiponectin levels observed in obese humans likely contribute to insulin resistance/diabetes and vascular disease. The mechanism(s) resulting in lower serum adiponectin in obese humans is not known. A reduction in adiponectin gene expression and secretion in adipose tissue from obese and obese diabetic subjects has been found in some (13,24,25,26,27), but not all (28), studies. The reason for this discrepancy is not clear. Furthermore, the role of omental vs. subcutaneous adipose tissue production of adiponectin has not been fully addressed. Therefore, in this study, we examined the expression of adiponectin mRNA in human subcutaneous and omental adipocytes obtained from women across a wide range of adiposity. In addition, we tested the hypothesis, based on observations in 3T3-L1 cells (29), that TNF and glucocorticoids are significant inhibitors of adiponectin synthesis and release from human adipocytes. Top of page

Research Methods and Procedures

Adipose Tissue Biopsy and Cell Culture Subcutaneous and omental adipose tissue biopsies were obtained from subjects undergoing bariatric surgical procedures. Subcutaneous adipose tissue from lean and obese subjects was also obtained by outpatient needle biopsy (30). Omental adipose tissue samples were also obtained from three lean women during open abdominal surgery for ulcerative colitis, stomach cancer, and colostomy. No subjects were taking diabetic medications (thiazolidinediones, insulin) that might affect adiponectin expression. All subjects provided informed consent, and the Institutional Review Boards of Indiana University-Purdue University at Indianapolis, IN, and St. Vincent's Hospital, Indianapolis, IN, approved all protocols. Adipocytes were isolated by collagenase (1 mg/mL) digestion as previously described (31) and used directly for RNA isolation or placed into culture. Adipocytes (1 mL packed cells) were suspension cultured in 5 mL Dulbecco's modified eagle medium (DMEM)/nutrient mixture F12 + 10% fetal bovine serum in 50 mL polypropylene centrifuge tubes kept on their sides at a 15 angle above horizontal, 37 C, and 5%CO2. The culture medium was replaced with fresh medium every 24 hours. Collagenase was from Worthington Biochemicals (Freehold, NJ). Culture medium (DMEM; D5523 and Nutrient Mixture F12; N6760) and dexamethasone (D2915; water soluble) were purchased from Sigma Chemical (St. Louis, MO). Fetal bovine serum was from Life Technologies (Grand Island, NY). TNF (210TA) was from R&D Systems (Minneapolis, MN). 3T3-L1 adipocytes were differentiated to mature adipocytes by standard techniques (32) and were used between 7 and 14 days after initiation of differentiation. Assays

Adiponectin, leptin, and insulin were measured with commercially available radioimmunoassay kits (Linco Research, St. Charles, MO). The limit of sensitivity of the adiponectin assay was 1 ng/mL, with an intra-and interassay precision of 6.21% and 6.90%, respectively, at a sample concentration of 3 g/mL. Adiponectin was measured in 100 L of culture medium in duplicate. The culture medium containing 10% FBS contained no detectable adiponectin. For leptin, the limit of detection was 0.5 ng/mL. The within- and between-assay coefficient of variation were 4.6% and 5.0%, respectively, at 7.2 ng/mL. Real-Time Reverse Transcription-Polymerase Chain Reaction Total RNA was isolated from adipocytes by standard methods. Adiponectin and leptin mRNA were quantitated using real-time reverse transcription-polymerase chain reaction (RT-PCR) following the Taqman Gold RT-PCR protocol (Applied Biosystems, Foster City, CA). We have previously documented no difference in RNA quality or gene expression in adipose tissue obtained from surgical procedures and needle biopsy (33). Total RNA (0.5 g) was reverse transcribed in a 100- L reaction. Primers (Invitrogen, Carlsbad, CA) and probes (Applied Biosystems) were designed using Primer Express software and GenBank entries XM003191 (human adiponectin) and NM000230 (human leptin). Adiponectin primers and probe were as follows: forward: 5'-AAGGAGATCCAGGTCTTATTGG-3', reverse: 5'ACCTTCAGCCCCGGGTAC-3', probe: 5'-CCTAAGGGAGACATCGGTGAAACCGG-3'. Leptin primers and probe were as follows: forward: 5'-TTTGGCCCTATCTTTTCTATGTCC-3', reverse: 5'-TGGAGGAGACTGACTGCGTG-3', probe: 5'-CCAAGATGACACCA-3'. To eliminate amplification of contaminating DNA, primer sets for both adiponectin and leptin crossed an intron-exon boundary. Expression of glyceraldehyde-3-phosphate dehydrogenase (primer and probes from Applied Biosystems, Foster City, CA) or -actin (34) was used to normalize adiponectin and leptin expression values. There was no difference in glyceraldehyde3-phosphate dehydrogenase or -actin expression between adipocytes from lean and obese subjects or between the omental and subcutaneous depots. Statistical Analyses All data are expressed as means SE. Pearson's correlation analysis was used to examine simple relationships between the measured variables. Inhibition of adiponectin or leptin release in culture experiments was examined by Student's paired t test. A p value <0.05 was considered significant. All statistical analyses were done using Statview 4.5 for Macintosh. Top of page

Results
To determine whether adiponectin expression is reduced in adipocytes from obese subjects, adiponectin mRNA was quantitated in subcutaneous adipocyte preparations from 32 women. As shown in Figure 1, there was a significant negative correlation between adiponectin mRNA and BMI. Adiponectin mRNA was significantly reduced 43% (p = 0.003) in the subcutaneous adipocytes of the obese (BMI 45.3 2.3 kg/m2; range, 28 to 61.9 kg/m2) subjects compared with

that in the lean (BMI 23.0 2.3 kg/m2; range, 21 to 26 kg/m2) subjects. Adiponectin mRNA was positively correlated with serum adiponectin (r = 0.44; p = 0.03; n = 25).
Figure 1.

Adiponectin mRNA in subcutaneous adipocytes is inversely correlated with adiposity. Values obtained for isolated adipocytes from 32 women. Full figure and legend (79K)

The reduction in serum adiponectin has been reported to be highly correlated with intraabdominal (omental) fat mass (35,36). Therefore, adiponectin mRNA expression was also examined in isolated omental adipocytes. There was no correlation between adiponectin mRNA expression and BMI (Figure 2, top) in mRNA preparations from 27 women. There was also no correlation between adiponectin mRNA and serum adiponectin (r = 0.311; p = 0.17; n = 21) or adiponectin mRNA and serum insulin (r = 0.05; p = 0.84; n = 23). Recognizing that the dataset for omental adipocytes was not balanced with respect to inclusion of an equal number of lean and obese subjects, LEP mRNA was analyzed using the same reverse transcribed cDNA as a control. As would be expected, LEP mRNA was significantly and positively correlated (r = 0.484; p = 0.01) with BMI in these samples (Figure 2, bottom). Furthermore, after removal of values for the three leaner women with BMI <30 kg/m2, LEP mRNA remained positively correlated with BMI (r = 0.394; p = 0.06).
Figure 2.

Adiponectin and leptin mRNA expression in omental adipocytes. (Top) Adiponectin mRNA expression is not correlated with adiposity. (Bottom) Leptin (LEP) gene expression is positively

correlated with adiposity in the same samples using the same reverse transcribed cDNA. Values obtained for isolated adipocytes from 27 women. Full figure and legend (54K)

To further examine adipose tissue adiponectin synthesis in obese subjects, adiponectin mRNA was quantitated in paired samples of omental and subcutaneous adipocytes derived from 19 women (BMI, 46.4 2.0 kg/m2; range, 32 to 58.4 kg/m2). There was no difference in adiponectin mRNA expression in these paired samples (17.0 2.2 vs. 16.8 1.9 relative expression units). Adiponectin secretion in vitro was examined in paired samples of subcutaneous and omental adipocytes from eight women (BMI, 52.9 4.3 kg/m2; range, 39.6 to 74 kg/m2). Release of adiponectin over 24 hours was not different between subcutaneous and omental adipocytes (16.1 3.2 vs. 17.0 3.3 ng/105 cells/24 h) derived from the same subject. These data suggest that adiponectin synthesis and release from omental and subcutaneous adipocytes in obese subjects is not different. An autocrine effect of TNF to inhibit adiponectin synthesis and release has been suggested as a possible explanation for lower serum adiponectin in obese subjects (29). To examine this hypothesis, subcutaneous and omental adipocytes from lean and obese subjects were cultured for 48 hours in the absence and presence of 100 ng/mL TNF . As shown in Table 1, adiponectin was continuously released into the medium over the entire 48-hour incubation period such that medium adiponectin concentrations were significantly greater at 48 hours than at 24 hours in all adipocyte preparations (p < 0.05). TNF had a small but significant effect on adiponectin release at 48 hours from adipocytes derived from lean subjects (7.4 1.2% inhibition; n = 9, p < 0.05). TNF also significantly inhibited leptin release (26.0 8.6%) from adipocytes of lean subjects (12.0 3.4 vs. 8.1 2.1 ng/mL; p = 0.04) with 48 hours of treatment. However, TNF had no effect on adiponectin release from subcutaneous or omental adipocytes derived from obese subjects (Table 1). Because of the marginal effect of TNF on adiponectin release from human adipocytes, differentiated 3T3-L1 cells were exposed to TNF for 24 hours to test the activity of the cytokine. As shown in Figure 3, at a 10-fold lower concentration than used in the human adipocyte culture experiments, TNF significantly reduced adiponectin release by 59.3 5.4%.
Figure 3.

TNF inhibits adiponectin release from 3T3-L1 adipocytes. Differentiated 3T3-L1 adipocytes were treated with TNF for 24 hours in DMEM + 10% fetal bovine serum. Adiponectin release to the culture medium was quantitated by radioimmunoassay. Values represent the mean SE for three separate experiments in which each treatment was performed in duplicate. * p = 0.02

Full figure and legend (64K)

Table 1. - Effect of TNF (100 ng/mL) on adiponectin release from isolated adipocytes.

Full table

Glucocorticoids have also been suggested to significantly inhibit adiponectin release in 3T3-L1 adipocytes (29). To determine whether glucocorticoids regulate release of adiponectin from human adipocytes, cells were treated with dexamethasone for 48 hours. As shown in Figure 4, dexamethasone (10-7 M) had a significant inhibitory effect on adiponectin release from subcutaneous adipocytes at both 24 (16.2 6.3%; p = 0.03) and 48 hours (12.5 4.5%; p = 0.03). Surprisingly, adiponectin release from omental adipocytes was unaltered by dexamethasone treatment (73.9 6.9 vs. 78.8 7.4 ng/mL released at 48 hours). The data suggest that glucocorticoids are more potent inhibitors of adiponectin release from human adipocytes than is TNF .
Figure 4.

Dexamethasone (DEX; 10-7 M) significantly inhibits adiponectin release from subcutaneous adipocytes. Values represent the mean SE for adipocyte preparations from 11 subjects (7 women and 4 men; BMI, 60.9 5.4 kg/m2). * p = 0.03 Full figure and legend (58K) Top of page

Discussion
It is well documented that serum adiponectin is significantly reduced in obese individuals, although the mechanism for this reduction remains poorly understood. In this study, we examined the possibility that the reduction in serum adiponectin in obesity is the result of

defective production by the adipocyte. We found that increasing adiposity is negatively correlated with adiponectin mRNA expression in abdominal subcutaneous adipocytes and that the reduction in adiponectin mRNA expression in subcutaneous adipocytes correlates with reduced serum adiponectin levels. In contrast, adiponectin mRNA in omental adipocytes was not correlated with adiposity or serum adiponectin. In paired samples of omental and subcutaneous adipocytes from obese subjects, adiponectin message was not different nor was adiponectin secretion different in vitro. Additional novel findings are that dexamethasone significantly inhibits adiponectin release from cultured human adipocytes but that TNF has only a marginal effect. Therefore, these results suggest that lower serum adiponectin levels in obese subjects result, at least in part, from reduced adiponectin synthesis in adipocytes but that TNF makes only a minor contribution to this effect. Several studies have examined adiponectin gene expression in human adipose tissue, but the results have been inconsistent. A reduction in adiponectin mRNA expression in subcutaneous adipose tissue of obese subjects has been observed in several (13,24,27) but not all studies (28). In omental adipose tissue, one study found reduced adiponectin mRNA in tissue from severely diabetic, obese subjects compared with that in lean normoglycemic individuals, but adiponectin expression in nondiabetic obese subjects was not different from that in lean controls (25). In other studies, adiponectin message in omental adipose tissue was either unrelated to BMI (28) or reduced in obese subjects (27). It has also been reported that adiponectin secretion in vitro from omental, but not subcutaneous, adipocytes is negatively correlated to BMI (26). It is not clear why such disparate results have been reported, but the use of adipose tissue from different sexes, which can be heterogeneous with respect to size and number of adipocytes per gram of tissue (37), may contribute to the discrepancies in these reports. In our study, we used isolated adipocytes from only women to avoid a possible confounding effect of sex, and we documented a significant 43% reduction in adiponectin mRNA in subcutaneous adipocytes from obese subjects. We also found that adiponectin mRNA expression in subcutaneous adipocytes was significantly correlated with serum adiponectin levels, suggesting that a reduction in adiponectin synthesis contributed to reduced serum hormone levels. We found no relationship between adiponectin mRNA expression in isolated omental adipocytes and BMI, in agreement with the report of Yang et al. (28), which used only adipose tissue from women, and Statnick et al. (25), that adiponectin mRNA is not reduced in omental adipocytes from nondiabetic obese subjects. However, a limitation of our finding is the unbalanced study group, which contains samples from only three lean (BMI < 30 kg/m2) women. Recognizing this, we examined LEP mRNA in the same samples and found a significant positive correlation with BMI. Interestingly, LEP mRNA expression remains correlated with BMI in these samples even if only those with BMI >30 kg/m2 are examined. This finding suggests that leptin expression is more strongly associated with adiposity in omental adipocytes than is adiponectin expression. Additional studies with more samples of omental adipose tissue from lean women will be needed to fully characterize the relationship between adiposity and adiponectin expression. The reduction in serum adiponectin is highly correlated with greater intraabdominal (omental) fat mass (35,36). This has led to the suggestion that synthesis and release of adiponectin from omental adipose tissue may be the major determinant of serum adiponectin levels. We found no difference in adiponectin mRNA expression or release of adiponectin in vitro from paired samples of omental and subcutaneous adipocytes from obese women. In agreement with two

other cross-sectional studies that did not find a significant difference in adiponectin message in omental and subcutaneous adipose tissue of obese subjects (27,28), this observation does not support the simple interpretation of the multiple regression analyses that adiponectin synthesis and release from omental adipocytes is less than that in subcutaneous adipocytes in obese subjects. Adipose tissuederived cytokines have been suggested to negatively regulate adiponectin synthesis and release. In particular, TNF and interleukin-6 have been shown to reduce adiponectin mRNA content and inhibit adiponectin release in 3T3-L1 cells (29,38). Surprisingly, we found that TNF (100 ng/mL) had no effect on adiponectin release from cultured subcutaneous or omental adipocytes derived from obese subjects, under conditions in which we previously observed significant 30% to 40% reductions in leptin release by 48 hours of treatment (39). One possibility for the lack of an effect of TNF on adiponectin release from adipocytes derived from obese subjects is that adiponectin synthesis/release is maximally inhibited at the time of adipocyte isolation, perhaps because of autocrine/paracrine effects of TNF in vivo, and that in vitro exposure could not further reduce adiponectin release. However, TNF induced only a small (7.4 1.2%) reduction in adiponectin release from adipocytes of lean subjects, in whom an elevation in adipose tissue TNF is not expected. Furthermore, leptin release from adipocytes of lean subjects was significantly reduced by 26.0 8.6%; a TNF -mediated inhibition of leptin release similar to that in adipocytes derived from obese subjects. Our data therefore suggest that TNF has, at best, only a modest effect on adiponectin release from human adipocytes. Bruun et al. (40) recently documented a TNF -induced reduction in adiponectin mRNA in cultured adipose tissue pieces from six lean women that required 48 hours of treatment. It is possible that TNF may stimulate release of additional factors from nonadipocytes in adipose tissue pieces that potentiate its effects on adiponectin mRNA, or alternatively, that preparation of isolated adipocytes reduces the efficacy of TNF compared with that in tissue pieces. Interestingly, in human preadipocytes differentiated in vitro, TNF inhibited adiponectin release by 50% at 48 hours of treatment (41), suggesting that differentiation of cells in vitro, either human or murine 3T3-L1, may result in an enhanced or different response to TNF than that of primary isolated cells. Indeed, TNF can induce dedifferentiation of 3T3-L1 adipocytes and human adipocytes differentiated in vitro (42), and this may explain the effect of the cytokine on adiponectin release in these models. Glucocorticoids are significant regulators of adipocyte function, and dysregulation of glucocorticoid metabolism by 11 HSD1 in adipose tissue has been implicated in obesity (4). Dexamethasone significantly inhibited adiponectin release from subcutaneous adipocytes of obese subjects with 24 hours of treatment, thus implicating this hormone in inhibition of adiponectin in vivo. Interestingly, dexamethasone had no effect on adiponectin release from omental adipocytes. This is surprising given that we previously documented greater dexamethasone-stimulated leptin production from omental, compared with subcutaneous, adipocytes (33). Halleux et al. (43) observed that dexamethasone reduced adiponectin mRNA in cultured omental adipose tissue pieces 20% and suggested that this effect was caused by induction of an autocrine/paracrine factor within the tissue that decreased the stability of adiponectin mRNA. The inability of dexamethasone to inhibit adiponectin release from isolated omental adipocytes in our study is consistent with the findings of Halleux et al. if the paracrine factor were produced by nonadipocytes within the adipose tissue, which would be absent in our

experiments. Although additional work will be needed to fully understand the different effect of dexamethasone on adiponectin synthesis and secretion in adipose tissue pieces vs. isolated omental adipocytes, glucocorticoids seem to be important regulators of adiponectin synthesis and release from human subcutaneous adipocytes. Our data suggest that reduced adiponectin gene expression in subcutaneous adipocytes contributes to lower serum adiponectin levels in obese subjects. However, a defect in adiponectin gene expression does not seem sufficient to fully explain the observed 30% to 50% decreases in serum adiponectin in obese subjects (6,7,8,9,10,11,12). Classic work from the laboratories of Hirsch and Knittle, Bjrntorp, and Salans et al. (44,45,46) established that there are, at a minimum, twice as many adipocytes in obese subjects compared with lean subjects and that, in some obese, there may be as many as 3.5 times more adipocytes. With twice as many adipocytes in the obese, a 50% reduction in gene expression in each adipocyte would be needed for serum adiponectin levels to be equal to that in lean subjects. Further reductions in adiponectin mRNA levels would thus be needed to reduce serum adiponectin below that in lean subjects if all of the reduction was linked directly to mRNA levels. Such large reductions in mRNA expression, which should be relatively easy to detect, were not found in our subjects and have not been reported in other studies. It is therefore likely that other factors also contribute to the decrease in serum adiponectin. A decrease in translation and secretion of adiponectin can be ruled out by the recent report of Hoffstedt et al. (47). These investigators found that, although the rate of adiponectin secretion from subcutaneous adipose tissue is reduced in obesity, the secretion rate seems to play only a minor role in the variation in serum adiponectin concentrations. Other possibilities might therefore include increased use and/or degradation of the circulating molecule in obese subjects. Future work should yield insight into these possibilities. In summary, we showed that adiponectin mRNA is significantly reduced in isolated subcutaneous adipocytes from obese subjects. Dexamethasone significantly inhibits adiponectin release from human adipocytes, but TNF has only a marginal effect. Additional work will be needed to fully understand the mechanism(s) that reduce serum adiponectin in obesity. Top of page

Notes
1

Nonstandard abbreviations: TNF, tumor necrosis factor; DMEM, Dulbecco modified eagles medium; RT-PCR, reverse transcription-polymerase chain reaction. Top of page

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Acknowledgments
We thank the subjects who donated samples for this research. We also thank the nursing staff of the Indiana University General Clinical Research Center and St. Vincent's Bariatric Center for assistance. The entero-insular axis and adipose tissue-related factors in the prediction of weight gain in humansSee all 11 matches for ReviewsRegulation of adiponectin release and demonstration of adiponectin mRNA as well as release by the non-fat cells of human omental adipose tissuePattern of expression of adiponectin receptors in human adipose tissue depots and its relation to the metabolic stateRelation of the Expression of Transcriptional Factor TFAP2B to That of Adipokines in Subcutaneous and Omental Adipose TissuesEffect of Marked Weight Loss on Adiponectin Gene Expression and Plasma Concentrations *See all 44 matches for ResearchJournal homeAccepted article previewAbout AAPAdvance online publicationAbout AOPCurrent issueArchiveWeb FocusIn the pressFACT or FICTION?Online submissionAuthor GuidelinesReviewer GuidelinesContact editorial officeAbout the journalAbout the societyFor librariansSubscribeAdvertising and salesReprints and permissionsContact NPGCustomer servicesSite featuresThe Obesity SocietyEuropean Journal of Clinical NutritionInternational Journal of Impotence ResearchJournal of Human HypertensionNature Reviews EndocrinologyNature Reviews Gastroenterology and HepatologyInternational Journal of ObesityAmerican Journal of HypertensionChemistryDrug discoveryBiotechnologyMaterialsMethods & ProtocolsCancerCardiovascular medicineDentistryEndocrinologyGastroenterology & HepatologyMethods & ProtocolsPathology & PathobiologyUrologyEarth sciencesEvolution & EcologyBiotechnologyCancerDevelopmentDrug discoveryEvolution & EcologyGeneticsImmunologyMedical researchMethods & ProtocolsMicrobiologyMolecular cell biologyNeurosciencePharmacologySystems biologyPhysicsMaterialsby A - Z IndexPreviousNextTable of contentsDownload PDFSend to a friendRights and permissionsOrder Commercial ReprintsSave this linkAbstractIntroductionResearch Methods and ProceduresResultsDiscussionNotesReferencesAcknowledgmentsFigures and TablesExport citationExport referencesPapers by Degawa-YamauchiTopCommittee on Publication Ethics

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