| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
Original Article |
Dorrance H. Hamilton Research Laboratories, Division of Endocrinology, Diabetes, and Metabolic Diseases, Department of Medicine (H.M., X.W., V.E.H., B.J.G.), and Department of Surgery (E.L.R., D.J.B., F.E.R.), Jefferson Medical College, Thomas Jefferson University, Philadelphia, Pennsylvania 19107; and Linco Research, Inc. (M.K.S.), St. Charles, Missouri 63304
Address all correspondence and requests for reprints to: Barry J. Goldstein, M.D., Ph.D., Director, Division of Endocrinology and Metabolic Diseases, Jefferson Medical College, Room 349 Alumni Hall, 1020 Locust Street, Philadelphia, Pennsylvania 19107-6799. E-mail: barry.goldstein{at}mail.tju.edu.
Abstract
Adiponectin is an adipocyte-derived plasma protein with insulin-sensitizing and antiatherosclerotic properties. Because adipose tissue depots differ in the strength of their association with the adverse metabolic consequences of obesity, we studied the secretion of adiponectin in vitro from paired samples of isolated human omental and sc adipocytes and its regulation by insulin and rosiglitazone. Cells were incubated for 12 or 24 h with and without treatment with 100 nM insulin, 8 µM rosiglitazone, or both combined; adiponectin secreted into the culture medium was measured by a RIA with a human adiponectin standard and normalized for cellular DNA content. Secretion of adiponectin by omental cells was generally higher than sc cells and showed a strong negative correlation with body mass index (r = -0.78;P = 0.013). In contrast, secretion from the sc cells was unrelated to body mass index. Compared with sc-derived adipocytes, adiponectin secretion from omental cells was increased by insulin or rosiglitazone alone and was up to 2.3-fold higher following combined treatment with insulin and rosiglitazone, whereas secretion from sc adipose cells was unaffected by these treatments. These data suggest that reduced secretion from the omental adipose depot may account for the decline in plasma adiponectin observed in obesity. Furthermore, enhanced adiponectin secretion from fat cells derived from the visceral compartment in response to rosiglitazone alone or in combination with insulin may play a role in some of the systemic insulin-sensitizing and antiinflammatory properties of the thiazolidinediones.
IN RECENT YEARS THE pathogenetic relationship among body adiposity, insulin resistance, and the onset of type 2 diabetes mellitus and its macrovascular complications have become better defined (1, 2). The deposition of stored triglyceride into certain adipose compartments, in particular the visceral abdominal fat depot, has consistently been shown to be associated with the multiple abnormalities in insulin signaling, glucose intolerance, hypertension, and dyslipidemia that characterize the metabolic syndrome and contribute to the increased risk for atherosclerosis and coronary disease in these patients (3). Compared with the sc depot, omental fat is relatively resistant to the antilipolytic effects of insulin, which contributes to the increase in circulating free fatty acid levels in subjects with an expanded omental adipose tissue mass (4). Elevated free fatty acids can block insulin signaling in skeletal muscle and liver, leading to compensatory hyperinsulinemia, and they can also have deleterious effects on endothelial function (5). In addition to enhanced lipolysis, differences in the secretion of cytokines and various other proteins among various adipose compartments may also play a role in the pathogenesis of the metabolic syndrome in subjects with increased visceral adiposity (6).
Adiponectin is a recently characterized addition to the family of adipose tissue secretory products that is purported to have novel insulin-sensitizing, antiatherogenic, and antiinflammatory properties (7, 8, 9). The relatively high plasma levels of this 30-kDa protein correlate negatively with obesity and insulin resistance in human subjects (10, 11, 12, 13), nonhuman primates (14), and rodents (8). Adiponectin levels are significantly lower in patients with coronary artery disease, and adiponectin can interact directly with endothelial cells to improve vascular function (11, 15, 16). Administration of adiponectin to obese or diabetic mice reduces circulating free fatty acid levels by enhanced skeletal muscle fat oxidation (17) and also reduces glucose excursions and enhances insulin sensitivity (18, 19, 20). Thus, the cellular effects of adiponectin may potentially link some of the metabolic and vascular abnormalities seen in patients with the metabolic syndrome.
Although these recent studies have demonstrated a close correlation between reduced plasma levels of adiponectin and obesity, insulin resistance, and cardiovascular disease, little is known about the cellular mechanisms regulating adiponectin secretion. Thiazolidinediones, currently used as insulin sensitizers in the treatment of patients with type 2 diabetes (21), have been shown to enhance the expression of adiponectin mRNA and plasma levels in human subjects (22) and animal models of insulin resistance and type 2 diabetes (23, 24, 25). Adiponectin has also been shown to be secreted from human visceral adipose tissue in vitro, and its mRNA appears to be negatively regulated by glucocorticoids and positively by insulin and IGF-I (26).
In the present work, we further evaluated whether adiponectin secretion differs between specific adipose tissue depots in human subjects and whether adiponectin secretion is regulated differentially in cells from these depots by insulin or thiazolidinediones. Our data show that adiponectin secretion from omental but not sc adipocytes correlates with obesity and is highly regulated by insulin and thiazolidinediones, suggesting that reduced secretion from the omental depot may account for most of the decline in plasma adiponectin observed in obesity and that some of therapeutic properties of the thiazolidinediones may result from their effects to increase adiponectin secretion from the visceral compartment.
Subjects and Methods
Study subjects
Following institutionally approved informed consent procedures, paired 8- to 10-g samples of omental and anterior abdominal sc adipose tissue were obtained at elective benign surgery or during gastric banding for obesity at Thomas Jefferson University Hospital in Philadelphia, Pennsylvania. None of the subjects had fasting hyperglycemia or was taking medication for diabetes mellitus. Before surgery all subjects were fasted overnight and only saline was infused iv until adipose tissue was removed, which was done at the beginning of surgery. The overall group of participants included nine subjects with mean age 48 yr (range, 29–82 yr) and a mean body mass index (BMI) of 40.6 kg/m2 (range, 21.5–57.6 kg/m2).
Materials
General reagents were of the highest available grade and obtained from Sigma (St. Louis, MO) or Fisher Scientific (Pittsburgh, PA). Rosiglitazone was generously provided by GlaxoSmithKline (Harlow, UK). DMEM, Ham’s F-12 culture medium, Hank’s solution, and fetal bovine serum were from Cellgro (Herndon, VA). DNA was purified using the Trizol reagent (Invitrogen, Carlsbad, CA). RIA kits for human adiponectin were obtained from Linco Research, Inc. (St. Charles, MO).
Adipocyte isolation and primary culture
Adipocytes were digested from the human adipose tissue samples and placed in culture as described (27). Under sterile conditions, freshly isolated adipose tissue obtained from the operating room was rinsed in warm Hank’s solution with antibiotics and chopped into small pieces. The fat tissue fragments were digested in DMEM:F-12 (50:50) medium containing 1% BSA, 1 mg/ml collagenase (type I) at 37 C for 40–60 min, and then filtered sequentially through sterile nylon mesh 500 µm, followed by 250 µm. Adipocytes were washed twice in warmed DMEM/F-12 medium containing antibiotics. After centrifugation at 800 x g for 5 min, adipocytes were transferred to a fresh DMEM/F12 medium in 50 ml Falcon tubes. The medium was removed under the adipocytes. Aliquots of 600 µl adipocytes were then cultured in 6-well culture dishes, with each well containing 4 ml DMEM/F-12 without fetal bovine serum or BSA.
Cell treatment and sampling
Where indicated, adipocytes were treated with recombinant human insulin (Sigma) at a final concentration of 100 nM, rosiglitazone at a final concentration of 8 µM (27), or a combined treatment of insulin and rosiglitazone at the same doses. Rosiglitazone was dissolved in a small volume of dimethylsulfoxide before addition to the culture medium, and an identical amount of the solvent was added to the control samples. Cells were incubated under an atmosphere of 5% CO2 in air at 37 C. Following culture for 12 or 24 h, 100 µl medium were sampled and immediately frozen and maintained at -85 C until use. Unconditioned medium was used as a blank control.
Measurement of adiponectin in cultured medium
RIA was used to measure the secretion of adiponectin into the medium of the cultured adipocytes, according to the manufacturer’s directions (Linco Research, Inc.). Samples of culture medium were analyzed in duplicate (100 µl). A human adiponectin standard provided in the kit was used as standard. To normalize for cell number in the assay, DNA was isolated from aliquots of each cell suspension and quantitated by spectrophotometry. Adiponectin secretion over a 12- or 24-h period is reported as nanograms per milliliter of culture medium per microgram cell DNA.
Statistical analyses
Quantitative data are expressed as the mean ± SE from replicate determinations. Student’s paired t test was used for comparing data from the samples derived from the two adipose depots from individual subjects, repeated-measures ANOVA was used for multiple comparisons, and correlation analyses were performed with the Pearson product moment technique (SigmaStat; SPSS, Inc., Chicago, IL). Differences were regarded as significant when the P value was less then 0.05.
Results
Basal adiponectin secretion
Adiponectin secretion into the culture medium by isolated sc and omental adipocytes was measured after 12 or 24 h of incubation. Using data pooled from all of the samples, the overall range of adiponectin secreted was wide, amounting to 0.67–3.23 ng/ml per microgram DNA at 12 h and 0.81–7.01 at 24 h by the sc adipocytes, 0.44–4.73 at 12 h, and 0.57–6.80 at 24 h by the omental adipocytes. In group mean data, basal adiponectin secretion was up to 28% higher from omental adipose cells, but the difference did not reach statistical significance (1.80 ± 0.28 vs. 2.32 ± 0.51 at 12 h, P = 0.35, 2.77 ± 0.60 vs. 3.49 ± 0.68 at 24 h, P = 0.31 in sc and omental adipocytes, respectively).
Correlation analysis between adiponectin secretion and BMI
Because previous studies demonstrated a decline in plasma adiponectin levels with obesity, we tested whether a correlation existed between adiponectin secretion from the omental or the sc adipocytes and BMI (Fig. 1
). Basal adiponectin secretion from omental adipocytes was strongly correlated in a negative fashion with BMI (r = -0.78; P = 0.013). In contrast, basal secretion from sc adipocytes was not associated with the subject’s BMI (r = 0.16, P = 0.97).
|
As indicated above, basal adiponectin secretion was not significantly different between sc and omental adipocytes. However, adiponectin secretion was stimulated differentially in the two depots by insulin and rosiglitazone treatment (Table 1). At 12 or 24 h, there were no significant changes in adiponectin secretion with any of the treatments using the sc adipocytes. Interestingly, there was a trend toward decreased adiponectin secretion with combined insulin and rosiglitazone treatment in the sc adipocytes at 12 and 24 h, by 20% and 23%, respectively. In contrast, at 12 h, using group mean data, adiponectin secretion using omental adipocytes was increased by combined insulin and rosiglitazone treatment by 40% over control samples. At 24 h, the increase in mean adiponectin secretion by omental adipocytes stimulated by either rosiglitazone alone or combined rosiglitazone and insulin treatment was 19–25% (Table 1).
|
). At 12 h, the omental samples stimulated with rosiglitazone alone also showed a 43% higher secretion rate of adiponectin, compared with sc adipocytes (P = 0.039), and at 24 h, the omental samples stimulated with rosiglitazone alone showed a 77% higher secretion rate of adiponectin, compared with sc adipocytes (P = 0.022). Adiponectin secretion responses from individual samples from the two adipocyte depots
To evaluate the amount of adiponectin secretion stimulated by the various treatments, we subtracted the basal level of secretion from each of the control samples from the stimulated level of secretion after the various treatments and then determined the mean and SE for each of the samples analyzed within the group (Fig. 2). These results show clearly that adiponectin secretion from sc adipocytes treated by insulin, rosiglitazone, or both together was not significantly different, compared with the level of basal adiponectin secretion and, in fact, trended downward. However, compared with sc adipocytes, the adiponectin secretion from omental adipocytes was significantly enhanced by incubation with insulin, rosiglitazone, or both treatments together, by 32%, 51%, and 83%, respectively, at 12 h (all P < 0.05 by repeated-measures ANOVA). At 24 h adiponectin secretion was also significantly increased by rosiglitazone or rosiglitazone combined with insulin at 24 h, by 41% and 65% (P < 0.05), respectively.
|
Because the range in adiponectin secretion among the grouped samples was relatively wide, we also compared adiponectin secretion from each of the paired omental and sc adipocytes from individual study participants following stimulation with combined insulin and rosiglitazone (Fig. 3). Increased adiponectin secretion from the omental adipocytes was observed for all but one of the subjects taken at the 24-h time point. At 12 and 24 h of stimulation, the 2.2- and 2.0-fold increase in adiponectin secretion observed from the individual omental samples, compared with the sc adipocytes, was significant by paired t test (P = 0.016 and 0.025, respectively).
|
The growing worldwide epidemic of obesity is projected to lead to a staggering 300 million people with type 2 diabetes by the yr 2025 (28). One of the major health implications of obesity and diabetes is the inherently increased risk for cardiovascular disease in these patients. Appropriately, attention has been directed recently toward a better understanding of the pathophysiological mechanisms underlying the association between visceral obesity and insulin resistance and how this condition leads to type 2 diabetes and the metabolic syndrome (2, 29). Major advances made in recent years include the recognition that adipose tissue is a highly secretory organ that releases a variety of factors that can affect both insulin action and endothelial function (30). The regional variation in adipocyte lipolytic responses and the differential expression of certain genes and secretory products has provided a framework from which to explore the differential impact of sc vs. visceral adipose tissue on clinical insulin resistance and cardiovascular risk (6, 31).
Adiponectin is a recently characterized adipose-specific secretory protein that has gained great interest as a novel mediator, having putative insulin-sensitizing and vascular protective effects that are opposite of the effects of other reported adipose tissue products such as including free fatty acids and TNF
(32, 33). Adiponectin is an abundant mRNA specific to mature adipose cells with relatively high levels in the blood of healthy human subjects (1.9–17.0 µg/ml) (8, 10, 11). Adiponectin is significantly decreased in rodents (8), monkeys (11), and human subjects with obesity and type 2 diabetes (11, 12, 13), and in particular in patients with coronary artery disease (15). Adiponectin levels correlate negatively with percentage body fat, central fat distribution, fasting plasma insulin, abnormal oral glucose tolerance, and correlate positively with glucose disposal during a euglycemic insulin clamp (8, 10, 11, 12, 13). Interestingly, the adiponectin gene maps to human chromosome 3q27 (34), a locus that has been associated with susceptibility to type 2 diabetes. Although plasma levels of adiponectin do not seem to change significantly in a diurnal or postprandial fashion, they increase significantly following weight loss in obese mice (18) and human subjects (11, 35).
In vitro studies have also recently shown that adiponectin has potentially important roles in the regulation of endothelial function as well as insulin action (9). Adiponectin binds specifically to a site on cultured human aortic endothelial cells and can reverse the effects of TNF to induce vascular cell adhesion molecule expression and leukocyte adhesion, possibly via suppression of nuclear factor 
B activation (15, 16). Adiponectin also has various effects in insulin-sensitive tissues that effectively improve insulin signaling and glucose metabolism. Administration of recombinant adiponectin has been directly shown to reduce circulating free fatty acid levels and enhance insulin suppression of hepatic glucose output, likely through cellular mechanisms involving enhanced fatty acid oxidation and decreased tissue triglyceride content (17, 18, 19, 20).
To gain insight into some of the regulatory processes affecting the plasma levels of adiponectin, we compared adiponectin secretion in vitro from adipocytes isolated from two major fat depots, sc and omental, which have been differentially implicated in the clinical insulin resistance associated with human obesity. Our data revealed that there is a wide distribution of adiponectin secretion rates among unrelated human subjects. Interestingly, we found that the adiponectin secretion in vitro from the omental adipose cells strongly correlated with the BMI of the study subjects in a negative fashion. This relationship was not apparent with the cells obtained from the sc fat depot. This suggests that the secretion of adiponectin from the omental compartment, which is markedly reduced in obesity, may largely account for previously reported inverse association between BMI and plasma levels of adiponectin. Considering the unique role for visceral adipose tissue in the pathogenesis of the metabolic syndrome, this finding is also consistent with the potential role for adiponectin on insulin sensitivity and normal vascular function.
We also sought to determine whether there were differences in the responsiveness of adiponectin secretion to treatment with insulin, rosiglitazone, or both combined in cells from the two depots. Adipocytes from various tissue depots are known to vary in their responsiveness to insulin with respect to suppression of lipolysis and other effects (4, 36). Our observation that omental adipose cells secrete more adiponectin in response to insulin than sc cells suggests that the increased level of circulating adiponectin in subjects with enhanced insulin sensitivity and improved insulin action following weight loss, for example (35), may be mediated by changes in adiponectin secretion from the visceral adipose depot as opposed to sc fat.
Only the omental adipose cells showed a sharp response to thiazolidinedione treatment, which was further enhanced by costimulation with insulin. These data support the notion that the increased circulating levels of adiponectin elicited by thiazolidinediones (22, 23, 24, 25) are derived from the omental rather than the sc compartment. Previous studies have shown a differential effect of thiazolidinediones on various adipose tissue depots, in particular affecting preadipocyte differentiation (37, 38, 39). Although the two major isoforms of the peroxisomal proliferator-activated receptor (PPAR) 
nuclear receptor are expressed in adipocytes from both of these tissue sources, and perhaps even at a higher level in the sc tissue (37), tissue differences in the cellular effects of PPAR activation may be determined by the abundance and activation state of various nuclear coactivator and corepressor proteins that modulate PPAR responses (40). The marked increase in the circulating levels of adiponectin following thiazolidinedione treatment may well play an important role in some of the insulin-sensitizing and vascular protective effects of these drugs (25).
To develop new approaches to the management of the cardiovascular consequences that accompany the worldwide epidemic of obesity and insulin resistance, it is essential that the pathogenetic mechanisms linking visceral adiposity with the components of the metabolic syndrome become fully defined. Among the growing family of adipocytokines secreted from adipose tissue, adiponectin has become a target of intensive study (9, 41). The results in the present study demonstrate a substantial variation in adiponectin secretion from two major adipose tissue depots. Unlike sc adipocytes, adiponectin secretion from omental adipocytes is reduced to a greater degree in more obese subjects and is sharply regulated by thiazolidinedione treatment, especially in combination with insulin. Further clarification of the mechanisms regulating the plasma levels of adiponectin may provide unique insight into some of the pathogenetic factors influencing the development of cardiovascular disease in patients with visceral obesity and type 2 diabetes.
Acknowledgments
We are grateful to Dr. Steven Smith and GlaxoSmithKline (Harlow, UK) for providing the rosiglitazone used in these studies.
Footnotes
This work was supported by NIH Grant R01-53388 (to B.J.G.).
H.M. and X.W. contributed equally to this work.
Abbreviations: BMI, Body mass index; PPAR, peroxisomal proliferator-activated receptor.
Received April 24, 2002.
Accepted May 29, 2002.
References
ligands increase expression and plasma concentrations of adiponectin, an adipose-derived protein. Diabetes 50:2094–2099 (PPAR ) deficiency and PPAR agonist improve insulin resistance. J Biol Chem 276:41245–41254 agonists: a potential mechanism of insulin sensitization. Endocrinology 143:998–1007 in the pathogenesis of insulin resistance and type 2 diabetes. Trends Endocrinol Metab 11:212–217[CrossRef][Medline]
and RXR agonists. Diabetes 51:718–723 have depot-specific effects on human preadipocyte differentiation. J Clin Invest 100:3149–3153[Medline]
This article has been cited by other articles:
 |
|
 |
|
  G. R. Hajer, T. W. van Haeften, and F. L.J. Visseren Adipose tissue dysfunction in obesity, diabetes, and vascular diseases Eur. Heart J., September 5, 2008; (2008) ehn387v1. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 N. Stefan, K. Kantartzis, J. Machann, F. Schick, C. Thamer, K. Rittig, B. Balletshofer, F. Machicao, A. Fritsche, and H.-U. Haring Identification and Characterization of Metabolically Benign Obesity in Humans Arch Intern Med, August 11, 2008; 168(15): 1609 - 1616. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, E. J. Boyko, M. J. McNeely, D. L. Leonetti, S. E. Kahn, and W. Y. Fujimoto Visceral Adiposity, Not Abdominal Subcutaneous Fat Area, Is Associated With an Increase in Future Insulin Resistance in Japanese Americans Diabetes, May 1, 2008; 57(5): 1269 - 1275. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Hojbjerre, M. Rosenzweig, F. Dela, J. M Bruun, and B. Stallknecht Acute exercise increases adipose tissue interstitial adiponectin concentration in healthy overweight and lean subjects Eur. J. Endocrinol., November 1, 2007; 157(5): 613 - 623. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. J. G. Hanley, D. Bowden, L. E. Wagenknecht, A. Balasubramanyam, C. Langfeld, M. F. Saad, J. I. Rotter, X. Guo, Y.-D. I. Chen, M. Bryer-Ash, et al. Associations of Adiponectin with Body Fat Distribution and Insulin Sensitivity in Nondiabetic Hispanics and African-Americans J. Clin. Endocrinol. Metab., July 1, 2007; 92(7): 2665 - 2671. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D Kapoor, S Clarke, R Stanworth, K S Channer, and T H Jones The effect of testosterone replacement therapy on adipocytokines and C-reactive protein in hypogonadal men with type 2 diabetes Eur. J. Endocrinol., May 1, 2007; 156(5): 595 - 602. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. H. Han, M. J. Quon, J.-a Kim, and K. K. Koh Adiponectin and Cardiovascular Disease: Response to Therapeutic Interventions J. Am. Coll. Cardiol., February 6, 2007; 49(5): 531 - 538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 E. W Demerath, W. Shen, M. Lee, A. C Choh, S. A Czerwinski, R. M Siervogel, and B. Towne Approximation of total visceral adipose tissue with a single magnetic resonance image Am. J. Clinical Nutrition, February 1, 2007; 85(2): 362 - 368. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. D Sniderman, R. Bhopal, D. Prabhakaran, N. Sarrafzadegan, and A. Tchernof Why might South Asians be so susceptible to central obesity and its atherogenic consequences? The adipose tissue overflow hypothesis Int. J. Epidemiol., February 1, 2007; 36(1): 220 - 225. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, E. J. Boyko, M. J. McNeely, D. L. Leonetti, S. E. Kahn, and W. Y. Fujimoto Minimum Waist and Visceral Fat Values for Identifying Japanese Americans at Risk for the Metabolic Syndrome Diabetes Care, January 1, 2007; 30(1): 120 - 127. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Phillips, O. A. Hatoum, and D. D. Gutterman The mechanism of flow-induced dilation in human adipose arterioles involves hydrogen peroxide during CAD Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H93 - H100. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Girard The Inhibitory Effects of Insulin on Hepatic Glucose Production Are Both Direct and Indirect Diabetes, December 1, 2006; 55(Supplement_2): S65 - S69. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Bansal, V. Charlton-Menys, P. Pemberton, P. McElduff, J. Oldroyd, A. Vyas, A. Koudsi, P. E. Clayton, J. K. Cruickshank, and P. N. Durrington Adiponectin in Umbilical Cord Blood Is Inversely Related to Low-Density Lipoprotein Cholesterol But Not Ethnicity J. Clin. Endocrinol. Metab., June 1, 2006; 91(6): 2244 - 2249. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. K. Ong, J. Frystyk, A. Flyvbjerg, C. J. Petry, the Avon Longitudinal Study of Parents and Childre, A. Ness, and D. B. Dunger Sex-Discordant Associations With Adiponectin Levels and Lipid Profiles in Children. Diabetes, May 1, 2006; 55(5): 1337 - 1341. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. L. Kuk, T. S. Church, S. N. Blair, and R. Ross Does Measurement Site for Visceral and Abdominal Subcutaneous Adipose Tissue Alter Associations With the Metabolic Syndrome? Diabetes Care, March 1, 2006; 29(3): 679 - 684. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Taleb, R. Cancello, C. Poitou, C. Rouault, P. Sellam, P. Levy, J.-L. Bouillot, C. Coussieu, A. Basdevant, M. Guerre-Millo, et al. Weight Loss Reduces Adipose Tissue Cathepsin S and Its Circulating Levels in Morbidly Obese Women J. Clin. Endocrinol. Metab., March 1, 2006; 91(3): 1042 - 1047. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Snijder, R. van Dam, M Visser, and J. Seidell What aspects of body fat are particularly hazardous and how do we measure them? Int. J. Epidemiol., February 1, 2006; 35(1): 83 - 92. [Full Text] [PDF]
|
|
|
|
 |
|
 N. Rasouli, A. Yao-Borengasser, L. M. Miles, S. C. Elbein, and P. A. Kern Increased plasma adiponectin in response to pioglitazone does not result from increased gene expression Am J Physiol Endocrinol Metab, January 1, 2006; 290(1): E42 - E46. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. G. Johns, Z. Ao, M. Eybye, A. Olzinski, M. Costell, S. Gruver, S. A. Smith, S. A. Douglas, and C. H. Macphee Rosiglitazone Protects against Ischemia/Reperfusion-Induced Leukocyte Adhesion in the Zucker Diabetic Fatty Rat J. Pharmacol. Exp. Ther., December 1, 2005; 315(3): 1020 - 1027. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. B. Tanko, Y. Z. Bagger, G. Qin, P. Alexandersen, P. J. Larsen, and C. Christiansen Enlarged Waist Combined With Elevated Triglycerides Is a Strong Predictor of Accelerated Atherogenesis and Related Cardiovascular Mortality in Postmenopausal Women Circulation, April 19, 2005; 111(15): 1883 - 1890. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Cote, P. Mauriege, J. Bergeron, N. Almeras, A. Tremblay, I. Lemieux, and J.-P. Despres Adiponectinemia in Visceral Obesity: Impact on Glucose Tolerance and Plasma Lipoprotein and Lipid Levels in Men J. Clin. Endocrinol. Metab., March 1, 2005; 90(3): 1434 - 1439. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 V. Sepilian and M. Nagamani Adiponectin Levels in Women With Polycystic Ovary Syndrome and Severe Insulin Resistance Reproductive Sciences, February 1, 2005; 12(2): 129 - 134. [Abstract] [PDF]
|
|
|
|
 |
|
 M. Grohmann, M. Sabin, J. Holly, J. Shield, E. Crowne, and C. Stewart Characterization of differentiated subcutaneous and visceral adipose tissue from children: the influences of TNF-{alpha} and IGF-I J. Lipid Res., January 1, 2005; 46(1): 93 - 103. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. M. Delaigle, J.-C. Jonas, I. B. Bauche, O. Cornu, and S. M. Brichard Induction of Adiponectin in Skeletal Muscle by Inflammatory Cytokines: in Vivo and in Vitro Studies Endocrinology, December 1, 2004; 145(12): 5589 - 5597. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
L. B. Tanko, J. M. Bruun, P. Alexandersen, Y. Z. Bagger, B. Richelsen, C. Christiansen, and P. J. Larsen Novel Associations Between Bioavailable Estradiol and Adipokines in Elderly Women With Different Phenotypes of Obesity: Implications for Atherogenesis Circulation, October 12, 2004; 110(15): 2246 - 2252. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. Winzer, O. Wagner, A. Festa, B. Schneider, M. Roden, D. Bancher-Todesca, G. Pacini, T. Funahashi, and A. Kautzky-Willer Plasma Adiponectin, Insulin Sensitivity, and Subclinical Inflammation in Women With Prior Gestational Diabetes Mellitus Diabetes Care, July 1, 2004; 27(7): 1721 - 1727. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Hayashi, E. J. Boyko, D. L. Leonetti, M. J. McNeely, L. Newell-Morris, S. E. Kahn, and W. Y. Fujimoto Visceral Adiposity Is an Independent Predictor of Incident Hypertension in Japanese Americans Ann Intern Med, June 15, 2004; 140(12): 992 - 1000. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Sutinen, K. Kannisto, E. Korsheninnikova, R. M. Fisher, E. Ehrenborg, T. Nyman, A. Virkamaki, T. Funahashi, Y. Matsuzawa, H. Vidal, et al. Effects of rosiglitazone on gene expression in subcutaneous adipose tissue in highly active antiretroviral therapy-associated lipodystrophy Am J Physiol Endocrinol Metab, June 1, 2004; 286(6): E941 - E949. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Urs, C. Smith, B. Campbell, A. M. Saxton, J. Taylor, B. Zhang, J. Snoddy, B. Jones Voy, and N. Moustaid-Moussa Gene Expression Profiling in Human Preadipocytes and Adipocytes by Microarray Analysis J. Nutr., April 1, 2004; 134(4): 762 - 770. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Hoffstedt, E. Arvidsson, E. Sjolin, K. Wahlen, and P. Arner Adipose Tissue Adiponectin Production and Adiponectin Serum Concentration in Human Obesity and Insulin Resistance J. Clin. Endocrinol. Metab., |
, male subjects; regression line (r = -0.079, P = 0.013); sc adipocytes: 
, female subjects; 
, male subjects; regression line (r = 0.16, P = 0.97).
