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Service de Biochimie (J.-P.B., C.J., P.B., B.H.), Hôpital de la Salpêtrière, AP-HP, Paris; Service de Biochimie et Hormonologie Hôpital Tenon-Rothschild (J.-P.B., J.C.), AP-HP, Paris; INSERM U-402 (J.-P.B., J.C.), Faculté de Médecine Saint-Antoine, Université Paris VI, Paris; Service d’Endocrinologie (E.B.), Hôpital de la Pitié, AP-HP, Paris; INSERM U-449 (M.L., H.V.), Faculté de Médecine RTH Laënnec, Lyon; and Département de Biochimie (B.H.), UFR de Pharmacie, Université Paris V, Paris, France
Address correspondence and requests for reprints to: Dr. Jean-Philippe Bastard, M.D., Ph.D., Service de Biochimie et Hormonologie, Hôpital Tenon, 4 rue de la Chine, 75970 Paris Cedex 20, France. E-mail: jean-philippe.bastard{at}tnn.ap-hop-paris.fr
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Abstract |
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 Top Abstract IntroductionSubjects and MethodsResultsDiscussionReferences |
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(TNF), and leptin in eight healthy lean control
females and in android obese female without (n = 14) and with
(n = 7) type 2 diabetes; and 2) the levels of these cytokines both
in serum and in sc adipose tissue in the 14 obese nondiabetic women
before and after 3 weeks of a very low-calorie diet (VLCD). As compared
with lean controls, obese nondiabetic and diabetic patients were more
insulin resistant and presented increased values for leptin, IL-6,
TNF, and C-reactive protein. In the whole group, IL-6 values were
more closely related to the parameters evaluating insulin resistance
than leptin or TNF values. VLCD resulted in weight loss and
decreased body fat mass (
3 kg). Insulin sensitivity was improved
with no significant change in both serum and adipose tissue TNF
levels. In contrast, VLCD induced significant decreases in IL-6 and
leptin levels in both adipose tissue and serum. These results suggest
that, as for leptin, circulating IL-6 concentrations reflect, at least
in part, adipose tissue production. The reduced production and serum
concentrations after weight loss could play a role in the improved
sensitivity to insulin observed in these patients. |
Introduction |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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(TNF) (3), and, more
recently, interleukin (IL)-6 (4). In the last years, an attractive
hypothesis has emerged proposing that those cytokines produced by
adipose tissue may be responsible for insulin resistance in obesity
(1). Indeed, the expression or production of these cytokines was shown
to be directly related to the degree of obesity of the subjects (1, 2, 3, 4)
and, thus, might be involved in obesity-related insulin resistance (1).
Leptin, the product of the ob gene (2), is primarily
produced by the adipocyte and has been shown to impair the metabolic
action of insulin in isolated rat adipocytes (5). However, other
studies suggest that leptin could also increase insulin sensitivity (6, 7). Therefore, the role of leptin in human insulin resistance in
vivo is still unclear. The deleterious effect of TNF on insulin
action has been presented in different experimental studies and is less
controversial during the inflammatory process (8, 9). Its mechanism of
action probably involves the phosphorylation of the insulin receptor
substrate-1 on serine residues resulting in a reduction in insulin
signaling into the cell (9). Increased expression of TNF messenger
RNA (mRNA) in the sc abdominal adipose tissue depot has been
documented in obese rodents and humans (3, 10, 11), leading to the
hypothesis that TNF may play a crucial role in obesity-related
insulin resistance (12). However, it was shown recently that human sc
adipose tissue does not release a significant amount of TNF in
vivo (4) and the relationship between adipose-derived TNF and
the in vivo insulin sensitivity in human is still largely
debated in the literature (13, 14, 15). Subcutaneous adipose tissue was
shown to secrete IL-6, and this secretion correlated with the body mass
index (BMI) of the subjects (4). The expression of IL-6 in human
adipose tissue was further confirmed (16). Thus, as a cytokine, IL-6
may play a role in obesity-related insulin resistance (1). However,
little is known about IL-6 expression and secretion in human adipose
tissue. In particular, it is not known whether adipose tissue and
plasma IL-6 levels change during weight loss and whether this could be
related to change in insulin sensitivity of the subjects.
In the present study, we aimed: 1) to compare serum concentrations of
IL-6, TNF, and leptin in healthy lean control subjects and in obese
patients with and without type 2 (non-insulin dependent) diabetes
mellitus; and 2) to measure the levels of these cytokines both in serum
and in sc adipose tissue in 14 obese women before and after 3 weeks of
a very low-calorie diet (VLCD).
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Subjects and Methods |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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Study 1.Twenty-nine Caucasian women volunteers [8 lean nondiabetic (age, 24–69 yr; BMI, 18.4–23.2 kg/m2), 14 nondiabetic obese (age, 28–64 yr; BMI, 32.9–48.7 kg/m2), and 7 type 2 diabetic obese women (age, 51–66 yr; BMI, 29.0–39.6 kg/m2)] were included in this study. Type 2 diabetes was assessed using the new American Diabetes Association criteria (17). Apart from obesity, all nondiabetic obese subjects were in good health and had stable body weight for at least 12 months. None was engaged in any type of exercise program or was excessively sedentary. All these subjects were involved in clinical investigations (18, 19) that were approved by the ethical committee of either the Hospice Civils de Lyon or the Assistance Publique-Hôpitaux de Paris and that were performed according to the French legislation. Blood samples were drawn in the morning (between 0800 and 0900 h) after an overnight fast.
Study 2.The 14 nondiabetic obese women participated in a VLCD program for 21 days. The energy intake was limited to 3.9 ± 0.1 MJ (941 ± 27 kcal)/day with 45% of carbohydrate, 20% of fat, and 35% of proteins. Subcutaneous abdominal adipose tissue biopsies were taken before and after 21 days of VLCD, after an overnight fast, using the percutaneous mini-liposuction method described previously (20). The two biopsies were taken from distinct sites, at the level of umbilicus. Subjects were still consuming the low-calorie diet at the time of the second biopsy. Adipose tissue samples were immediately frozen in liquid nitrogen and stored at -80 C until protein analysis. All subjects had given their written consent after being informed of the nature, purpose, and possible risks of the study. The experimental protocol was approved by the ethical committee of Assistance Publique-Hôpitaux de Paris and performed according to the French legislation (Huriet law).
Analytical methods
Venous blood samples were taken between 0800 and 0900 h,
after an overnight fast, before, and at the end of the diet period and
stored at -80 C before immuno-assays analysis. Blood glucose was
assayed enzymatically (hexokinase) using a multiparametric analyzer
(Hitachi 911; Roche Molecular Biochemicals, Meylan,
France). Serum insulin concentrations were measured using commercial
RIA kits (Bi-Insulin IRMA; ERIA-Pasteur, Paris, France). Serum levels
of leptin, TNF, and IL-6 were determined by enzyme-linked
immunosorbent assay (Quantikine leptin; Quantikine High Sensitivity
TNF and Quantikine IL-6; R&D Systems, Oxford, UK). The sensitivity
of these assays was 7.8 pg/mL, 0.18 pg/mL, and 0.70 pg/mL for leptin,
TNF, and IL-6, respectively. The same enzyme-linked immunosorbent
assay kits were used to determine the immunoreactive leptin, TNF,
and IL-6 protein content in adipose tissue samples after homogenization
of 200 mg frozen tissue in 400 µL of a buffer (pH 7.4) containing 10
mmol/of Tris-HCl, 250 mmol/l of sucrose, and a mixture of protease
inhibitors (Complete; Roche Molecular Biochemicals). C
reactive protein (CRP) was assessed by immuno-nephelometry on Behring
Nephelometer 2 (Dade-Behring, La Défense, France). The
sensitivity of the assay was 0.18 mg/L. Estimation of insulin
resistance in the fasting state [fasting insulin resistance index
(FIRI)] was calculated from fasting plasma glucose and insulin levels
(FIRI = fasting glucose x fasting insulin/25) (21). A body
composition analysis by dual x-ray absorptiometry was performed in the
nondiabetic obese women only, using the QDR 1000 from Hologic, Inc. (Waltham, MA).
Presentation of the results
All results are presented as mean ± SE. Nonparametric Wilcoxon’s rank-sum test for paired data was used to compare values before and after diet. Differences between groups were determined using one-way ANOVA and the Kruskal-Wallis test, followed by a Fisher protected least significant test for pair-wise differences. The significance of the correlations was examined using the nonparametric Spearman’s rank correlation test. Multiple regression analysis was undertaken for the continuous variable, IL-6. The threshold for significance was set at P = 0.05.
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Results |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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, and leptin and of CRP
were significantly higher in diabetic and nondiabetic obese women than
in healthy lean subjects (Table 1
).
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, and leptin were significantly
correlated with BMI and fasting plasma insulin levels when the 29
subjects were analyzed together (Table 2). IL-6 and leptin concentrations were
significantly correlated with serum CRP levels and waist to hip ratio,
whereas serum TNF levels were not (Table 2). Moreover, only IL-6
concentrations correlated significantly with fasting plasma glucose
levels and the FIRI (Fig. 1). There was
no correlation between these two parameters and either TNF or leptin
concentrations (Table 2). Therefore, IL-6 values were more strongly
correlated with obesity and insulin resistance parameters than TNF
or leptin. To investigate which variables might account for the
association between circulating IL-6 levels and insulin resistance,
multiple regression analysis was performed. The independent variables
used in this analysis were the variables significantly correlated with
IL-6 in univariate analysis (i.e. BMI, waist to hip ratio,
FIRI, fasting plasma glucose, and insulin). In the whole group, only
BMI (P < 0.05) and FIRI (P < 0.05)
were independently and significantly associated with IL-6 levels.
Finally, when each of the three group of subjects were analyzed
separately, only leptin remained significantly associated with BMI in
the obese nondiabetic group (r = 0.666, P <
0.05).
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). During VLCD, serum IL-6
concentration decreased slightly but significantly (P =
0.05) in all subjects whereas the changes in serum CRP levels did not
reach significance (P = 0.14). VLCD also produced a
significant decrease in serum leptin concentration (P
< 0.005). In contrast to what was observed with IL-6 and leptin, serum
TNF concentration remained unchanged after VLCD.
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protein remained unchanged
(P = 0.36, Fig. 2). These
variations reflect those observed at the serum level.
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Discussion |
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TopAbstractIntroductionSubjects and MethodsResultsDiscussionReferences |
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, and leptin were increased in nondiabetic and diabetic
obese women when compared with healthy lean women. Moreover, serum
levels of IL-6, TNF, and leptin were significantly correlated with
the BMI of the subjects, suggesting that the circulating concentrations
of these cytokines may reflect, at least in part, production by adipose
tissue. Interestingly, serum CRP levels were also elevated both in the
nondiabetic and diabetic obese women as compared with controls,
suggesting that obesity may also influence serum CRP concentrations.
CRP is an acute phase inflammatory protein in which production results
from the IL-1, IL-6, and TNF balance in human, and it was suggested
recently that its serum concentration may be regulated, at least in
part, by adipose tissue IL-6 secretion in the basal state (16, 22). The
observed correlation between the serum concentrations of IL-6 and CRP
is in line with this hypothesis. Because it was already observed by
others (23, 24), we found a positive relationship between circulating
IL-6 and the degree of obesity estimated by the BMI. One of the
possible mechanisms whereby IL-6 level is increased in obesity could be
due to the fact that adipose tissue is able to express (16, 25) and to
secrete IL-6 (26) and that IL-6 production from adipose tissue is
higher in obese subjects (4). However, the molecular mechanism for the
increased expression of IL-6 in adipocytes from obese subjects is
presently unknown.
Fasting serum concentrations of IL-6 were associated with all the
markers of insulin resistance measured in the study (fasting plasma
levels of insulin and glucose, FIRI, and waist to hip ratio), whereas
the concentrations of TNF were only associated with plasma insulin
and those of leptin with plasma insulin and waist to hip ratio. This
result may suggest, in agreement with the finding of Mohamed-Ali
et al. (4), that IL6 concentration is more closely
associated with obesity-related insulin resistance than TNF or
leptin in humans. Indeed, for the first time, we showed a direct
positive correlation between insulin resistance and circulating IL-6
levels in human (Fig. 1
). Some recent published works are in line with
this finding, suggesting a link between insulin resistance and
circulating IL-6 levels in different diseases such as sleep apnea with
visceral obesity (24), patients with cancer (27), or patients with
Syndrome X (28) or at risk for coronary heart disease (22, 29). The
mechanisms whereby IL-6 can induce insulin resistance at the cellular
level are poorly understood. However, it has been reported that IL-6
induced physiological changes reminiscent of the catabolic state with
increased plasma free fatty acids and fat oxidation (30) and inhibition
of adipose tissue lipoprotein lipase activity (31): all these effects
are opposite to those of insulin, therefore, impairing insulin action.
On the same line, IL-6 has been shown recently to have effects opposite
of those of insulin on hepatic glycogen metabolism (32), and IL-6 was
shown to increase glycemia (33). The role of adipose tissue IL-6 in
obesity was suggested by Mohamed-Ali et al. (4), who have
demonstrated that adipose tissue in human is able to secrete a large
amount of IL-6 with an increased production in obese subjects and that
this secretion may account for about 25% of the circulating IL-6
concentrations in the basal state, while no significant secretion of
TNF from sc adipose tissue was found (4). In addition, in line with
previous works from others (23, 24), our results suggest a link between
IL-6 and obesity. It is, thus, possible that adipose tissue-derived
IL-6 may be involved in obesity-associated insulin resistance.
Leptinemia decreased significantly during VLCD in agreement with previous reports on the effect of dieting in obese subjects (19, 34, 35). This decrease in the circulating concentration of leptin was most probably a consequence of a reduction in leptin expression and production in fat as supported by the decrease in leptin protein content in adipose tissue after VLCD and also by the decrease in leptin mRNA levels that was previously described in obese patients under diet (19).
In contrast to what was observed for leptin, the serum concentrations
and the protein contents in adipose tissue of TNF remained unchanged
during VLCD in our study. The regulation of TNF levels both in serum
and in adipose tissue after weight loss in human obesity is still a
matter of debate (10, 11, 19, 36, 37). It was reported that a 2-yr
dieting program decreased circulating serum TNF in obese women (36).
This result was in line with studies showing that diet-induced weight
loss in obese patients was associated with decreased expression of
TNF in sc adipose tissue after stabilization of weight (10, 11). In
contrast, we have recently shown that the dynamic period of weight loss
during VLCD was associated with an increase in TNF mRNA expression
in adipose tissue of largely obese women (19). Here, we found that
fasting serum levels of TNF was unchanged after 3 weeks of VLCD. A
lack of change in plasma TNF concentration was also recently
observed in obese individuals after a large weight loss (20–30 kg) 1
yr after gastroplasty (37). These discrepancies may be due to the
difference in the mechanisms involved in weight loss in these studies
[i.e. diet (10, 11, 19, 36) or gastroplasty (37)] and the
period chosen to study this weight loss [i.e. dynamic (19)
or stabilization period (10, 11, 36)]. Therefore, the contribution of
adipose tissue to the circulating levels of TNF in human obesity is
still unclear.
In the present study, we report for the first time changes in IL-6 protein concentrations after VLCD both in adipose tissue and in serum in obese subjects. Adipose tissue IL-6 content decreased significantly after VLCD and was associated with a slight decrease in serum IL-6 concentrations. However, none of the observed modifications in IL-6 expression was directly associated with the loss in weight or in fat mass (data not shown). It is probable that the observed variations result from severe diet rather than from fat mass loss because IL-6 has been shown to be acutely stimulated by meals (26) and because the amount of fat loss represent only a few percentages of the total fat mass in these obese patients. Moreover, such a nutritional regulation has already been reported for leptin (31), another cytokine synthesized and secreted by adipose tissue. These results are in line with the fact that IL-6 production by adipose tissue could explain 10–30% of the whole circulating IL-6 concentration (1). IL-6 is the major stimulating factor for hepatocyte synthesis and secretion of CRP in human. Interestingly, we found that serum CRP tended to decrease during weight loss, indicating a possible link between adipose tissue secretion of IL-6, the regulation of systemic IL-6 circulating levels, and IL-6 function in the basal state without any acute inflammation.
In conclusion, this study demonstrates that elevated circulating IL-6 levels are associated with obesity in women. Moreover, adipose tissue may participate, in part, to the serum IL-6 concentrations, particularly during VLCD-induced weight loss, a situation that was associated with a decrease in both adipose tissue and serum IL-6 contents. Additional investigations are now required to verify whether modifications in the IL-6 system are involved in or are the result of the reduction of adipose tissue mass and their role in the improvement of insulin sensitivity observed after weight loss.
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Footnotes |
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Received January 10, 2000.
Revised May 23, 2000.
Accepted June 15, 2000.
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M. A. Schrager, E. J. Metter, E. Simonsick, A. Ble, S. Bandinelli, F. Lauretani, and L. Ferrucci Sarcopenic obesity and inflammation in the InCHIANTI study J Appl Physiol, March 1, 2007; 102(3): 919 - 925. [Abstract] [Full Text] [PDF]
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R. A. Mooney COUNTERPOINT: INTERLEUKIN-6 DOES NOT HAVE A BENEFICIAL ROLE IN INSULIN SENSITIVITY AND GLUCOSE HOMEOSTASIS J Appl Physiol, February 1, 2007; 102(2): 816 - 818. [Full Text] [PDF]
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B. K. Pedersen, M. A. Febbraio, and R. A. Mooney Interleukin-6 does/does not have a beneficial role in insulin sensitivity and glucose homeostasis J Appl Physiol, February 1, 2007; 102(2): 814 - 816. [Full Text] [PDF]
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 E. Selvin, N. P. Paynter, and T. P. Erlinger The Effect of Weight Loss on C-Reactive Protein: A Systematic Review Arch Intern Med, January 8, 2007; 167(1): 31 - 39. [Abstract] [Full Text] [PDF]
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E. Klimcakova, J. Polak, C. Moro, J. Hejnova, M. Majercik, N. Viguerie, M. Berlan, D. Langin, and V. Stich Dynamic Strength Training Improves Insulin Sensitivity without Altering Plasma Levels and Gene Expression of Adipokines in Subcutaneous Adipose Tissue in Obese Men J. Clin. Endocrinol. Metab., December 1, 2006; 91(12): 5107 - 5112. [Abstract] [Full Text] [PDF]
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F. Samad, K. D. Hester, G. Yang, Y. A. Hannun, and J. Bielawski Altered Adipose and Plasma Sphingolipid Metabolism in Obesity: A Potential Mechanism for Cardiovascular and Metabolic Risk Diabetes, September 1, 2006; 55(9): 2579 - 2587. [Abstract] [Full Text] [PDF]
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 G. G. Gosman, H. I. Katcher, and R. S. Legro Obesity and the role of gut and adipose hormones in female reproduction Hum. Reprod. Update, September 1, 2006; 12(5): 585 - 601. [Abstract] [Full Text] [PDF]
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M J Kim, M Maachi, C Debard, E Loizon, K Clement, E Bruckert, B Hainque, J Capeau, H Vidal, and J P Bastard Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss. Eur. J. Endocrinol., July 1, 2006; 155(1): 161 - 165. [Abstract] [Full Text] [PDF]
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F. Andreozzi, E. Laratta, M. Cardellini, M. A. Marini, R. Lauro, M. L. Hribal, F. Perticone, and G. Sesti Plasma interleukin-6 levels are independently associated with insulin secretion in a cohort of italian-caucasian nondiabetic subjects. Diabetes, July 1, 2006; 55(7): 2021 - 2024. [Abstract] [Full Text] [PDF]
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P. Trayhurn, C. Bing, and I. S. Wood Adipose Tissue and Adipokines--Energy Regulation from the Human Perspective J. Nutr., July 1, 2006; 136(7): 1935S - 1939S. [Abstract] [Full Text] [PDF]
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 A. Guven, A. Cetinkaya, M. Aral, G. Sokmen, M. A. Buyukbese, A. Guven, and N. Koksal High-Sensitivity C-Reactive Protein in Patients with Metabolic Syndrome Angiology, May 1, 2006; 57(3): 295 - 302. [Abstract] [PDF]
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J. M. Bruun, J. W. Helge, B. Richelsen, and B. Stallknecht Diet and exercise reduce low-grade inflammation and macrophage infiltration in adipose tissue but not in skeletal muscle in severely obese subjects Am J Physiol Endocrinol Metab, May 1, 2006; 290(5): E961 - E967. [Abstract] [Full Text] [PDF]
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E. Corpeleijn, W. H. M. Saris, E. H. J. M. Jansen, P. M. H. J. Roekaerts, E. J. M. Feskens, and E. E. Blaak Postprandial Interleukin-6 Release from Skeletal Muscle in Men with Impaired Glucose Tolerance Can Be Reduced by Weight Loss J. Clin. Endocrinol. Metab., October 1, 2005; 90(10): 5819 - 5824. [Abstract] [Full Text] [PDF]
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 Z. T. Bloomgarden Inflammation, Atherosclerosis, and Aspects of Insulin Action Diabetes Care, September 1, 2005; 28(9): 2312 - 2319. [Full Text] [PDF]
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 D. Rothenbacher, H. Brenner, W. Marz, and W. Koenig Adiponectin, risk of coronary heart disease and correlations with cardiovascular risk markers Eur. Heart J., August 2, 2005; 26(16): 1640 - 1646. [Abstract] [Full Text] [PDF]
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T. Skurk, H. Kolb, S. Muller-Scholze, K. Rohrig, H. Hauner, and C. Herder The proatherogenic cytokine interleukin-18 is secreted by human adipocytes Eur. J. Endocrinol., June 1, 2005; 152(6): 863 - 868. [Abstract] [Full Text] [PDF]
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J. C Hogan and J. M Stephens Effects of leukemia inhibitory factor on 3T3-L1 adipocytes J. Endocrinol., June 1, 2005; 185(3): 485 - 496. [Abstract] [Full Text] [PDF]
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The Diabetes Prevention Program Research Group Intensive Lifestyle Intervention or Metformin on Inflammation and Coagulation in Participants With Impaired Glucose Tolerance Diabetes, May 1, 2005; 54(5): 1566 - 1572. [Abstract] [Full Text] [PDF]
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 B. J. Nicklas, T. You, and M. Pahor Behavioural treatments for chronic systemic inflammation: effects of dietary weight loss and exercise training Can. Med. Assoc. J., April 26, 2005; 172(9): 1199 - 1209. [Abstract] [Full Text] [PDF]
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D. D. Christou, C. L. Gentile, C. A. DeSouza, D. R. Seals, and P. E. Gates Fatness Is a Better Predictor of Cardiovascular Disease Risk Factor Profile Than Aerobic Fitness in Healthy Men Circulation, April 19, 2005; 111(15): 1904 - 1914. [Abstract] [Full Text] [PDF]
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G. Rega, C. Kaun, T.W. Weiss, S. Demyanets, G. Zorn, S.P. Kastl, S. Steiner, D. Seidinger, C.W. Kopp, M. Frey, et al. Inflammatory Cytokines Interleukin-6 and Oncostatin M Induce Plasminogen Activator Inhibitor-1 in Human Adipose Tissue Circulation, April 19, 2005; 111(15): 1938 - 1945. [Abstract] [Full Text] [PDF]
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 H. F. Escobar-Morreale, M. Luque-Ramirez, and J. L. San Millan The Molecular-Genetic Basis of Functional Hyperandrogenism and the Polycystic Ovary Syndrome Endocr. Rev., April 1, 2005; 26(2): 251 - 282. [Abstract] [Full Text] [PDF]
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J. M. Bruun, A. S. Lihn, S. B. Pedersen, and B. Richelsen Monocyte Chemoattractant Protein-1 Release Is Higher in Visceral than Subcutaneous Human Adipose Tissue (AT): Implication of Macrophages Resident in the AT J. Clin. Endocrinol. Metab., April 1, 2005; 90(4): 2282 - 2289. [Abstract] [Full Text] [PDF]
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R. Takeda, E. Suzuki, H. Satonaka, S. Oba, H. Nishimatsu, M. Omata, T. Fujita, R. Nagai, and Y. Hirata Blockade of Endogenous Cytokines Mitigates Neointimal Formation in Obese Zucker Rats Circulation, March 22, 2005; 111(11): 1398 - 1406. [Abstract] [Full Text] [PDF]
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P. Trayhurn Adipose Tissue in Obesity--An Inflammatory Issue Endocrinology, March 1, 2005; 146(3): 1003 - 1005. [Full Text] [PDF]
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T. Skurk, C. Herder, I. Kraft, S. Muller-Scholze, H. Hauner, and H. Kolb Production and Release of Macrophage Migration Inhibitory Factor from Human Adipocytes Endocrinology, March 1, 2005; 146(3): 1006 - 1011. [Abstract] [Full Text] [PDF]
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S. Klein, L. E. Burke, G. A. Bray, S. Blair, D. B. Allison, X. Pi-Sunyer, Y. Hong, and R. H. Eckel Clinical Implications of Obesity With Specific Focus on Cardiovascular Disease: A Statement for Professionals From the American Heart Association Council on Nutrition, Physical Activity, and Metabolism: Endorsed by the American College of Cardiology Foundation Circulation, November 2, 2004; 110(18): 2952 - 2967. [Abstract] [Full Text] [PDF]
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 L. Khaodhiar, P.-R. Ling, G. L. Blackburn, and B. R. Bistrian Serum Levels of Interleukin-6 and C-Reactive Protein Correlate With Body Mass Index Across the Broad Range of Obesity JPEN J Parenter Enteral Nutr, November 1, 2004; 28(6): 410 - 415. [Abstract] [Full Text] [PDF]
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M. E. Trujillo, S. Sullivan, I. Harten, S. H. Schneider, A. S. Greenberg, and S. K. Fried Interleukin-6 Regulates Human Adipose Tissue Lipid Metabolism and Leptin Production in Vitro J. Clin. Endocrinol. Metab., November 1, 2004; 89(11): 5577 - 5582. [Abstract] [Full Text] [PDF]
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 K. CLEMENT, N. VIGUERIE, C. POITOU, C. CARETTE, V. PELLOUX, C. A. CURAT, A. SICARD, S. ROME, A. BENIS, J.-D. ZUCKER, et al. Weight loss regulates inflammation-related genes in white adipose tissue of obese subjects FASEB J, November 1, 2004; 18(14): 1657 - 1669. [Abstract] [Full Text] [PDF]
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D. Seboek, P. Linscheid, H. Zulewski, I. Langer, M. Christ-Crain, U. Keller, and B. Muller Somatostatin Is Expressed and Secreted by Human Adipose Tissue upon Infection and Inflammation J. Clin. Endocrinol. Metab., October 1, 2004; 89(10): 4833 - 4839. [Abstract] [Full Text] [PDF]
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J. A. McKenzie, E. P. Weiss, I. A. Ghiu, O. Kulaputana, D. A. Phares, R. E. Ferrell, and J. M. Hagberg Influence of the interleukin-6 -174 G/C gene polymorphism on exercise training-induced changes in glucose tolerance indexes J Appl Physiol, October 1, 2004; 97(4): 1338 - 1342. [Abstract] [Full Text] [PDF]
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J. M. Harkins, N. Moustaid-Moussa, Y.-J. Chung, K. M. Penner, J. J. Pestka, C. M. North, and K. J. Claycombe Expression of Interleukin-6 Is Greater in Preadipocytes than in Adipocytes of 3T3-L1 Cells and C57BL/6J and ob/ob Mice J. Nutr., October 1, 2004; 134(10): 2673 - 2677. [Abstract] [Full Text] [PDF]
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 K. Okita, H. Nishijima, T. Murakami, T. Nagai, N. Morita, K. Yonezawa, K. Iizuka, H. Kawaguchi, and A. Kitabatake Can Exercise Training With Weight Loss Lower Serum C-Reactive Protein Levels? Arterioscler Thromb Vasc Biol, October 1, 2004; 24(10): 1868 - 1873. [Abstract] [Full Text] [PDF]
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 M. Lambert, E. E. Delvin, G. Paradis, J. O'Loughlin, J. A. Hanley, and E. Levy C-Reactive Protein and Features of the Metabolic Syndrome in a Population-Based Sample of Children and Adolescents Clin. Chem., October 1, 2004; 50(10): 1762 - 1768. [Abstract] [Full Text] [PDF]
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 K. Esposito, R. Marfella, M. Ciotola, C. Di Palo, F. Giugliano, G. Giugliano, M. D'Armiento, F. D'Andrea, and D. Giugliano Effect of a Mediterranean-Style Diet on Endothelial Dysfunction and Markers of Vascular Inflammation in the Metabolic Syndrome: A Randomized Trial JAMA, September 22, 2004; 292(12): 1440 - 1446. [Abstract] [Full Text] [PDF]
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J. Rieusset, K. Bouzakri, E. Chevillotte, N. Ricard, D. Jacquet, J.-P. Bastard, M. Laville, and H. Vidal Suppressor of Cytokine Signaling 3 Expression and Insulin Resistance in Skeletal Muscle of Obese and Type 2 Diabetic Patients Diabetes, September 1, 2004; 53(9): 2232 - 2241. [Abstract] [Full Text] [PDF]
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E. Arvidsson, N. Viguerie, I. Andersson, C. Verdich, D. Langin, and P. Arner Effects of Different Hypocaloric Diets on Protein Secretion From Adipose Tissue of Obese Women Diabetes, August 1, 2004; 53(8): 1966 - 1971. [Abstract] [Full Text] [PDF]
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A. S. Ryan and B. J. Nicklas Reductions in Plasma Cytokine Levels With Weight Loss Improve Insulin Sensitivity in Overweight and Obese Postmenopausal Women Diabetes Care, July 1, 2004; 27(7): 1699 - 1705. [Abstract] [Full Text] [PDF]
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G. B. Di Gregorio, L. Hensley, T. Lu, G. Ranganathan, and P. A. Kern Lipid and carbohydrate metabolism in mice with a targeted mutation in the IL-6 gene: absence of development of age-related obesity Am J Physiol Endocrinol Metab, July 1, 2004; 287(1): E182 - E187. [Abstract] [Full Text] [PDF]
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K. Esposito, F. Giugliano, C. Di Palo, G. Giugliano, R. Marfella, F. D'Andrea, M. D'Armiento, and D. Giugliano Effect of Lifestyle Changes on Erectile Dysfunction in Obese Men: A Randomized Controlled Trial JAMA, June 23, 2004; 291(24): 2978 - 2984. [Abstract] [Full Text] [PDF]
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C. E. Juge-Aubry, E. Somm, R. Chicheportiche, D. Burger, A. Pernin, B. Cuenod-Pittet, P. Quinodoz, V. Giusti, J.-M. Dayer, and C. A. Meier Regulatory Effects of Interleukin (IL)-1, Interferon-{beta}, and IL-4 on the Production of IL-1 Receptor Antagonist by Human Adipose Tissue J. Clin. Endocrinol. Metab., June 1, 2004; 89(6): 2652 - 2658. [Abstract] [Full Text] [PDF]
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J. Faldt, I. Wernstedt, S. M. Fitzgerald, K. Wallenius, G. Bergstrom, and J.-O. Jansson Reduced Exercise Endurance in Interleukin-6-Deficient Mice Endocrinology, June 1, 2004; 145(6): 2680 - 2686. [Abstract] [Full Text] [PDF]
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B. J Nicklas, W. Ambrosius, S. P Messier, G. D Miller, B. W. Penninx, R. F Loeser, S. Palla, E. Bleecker, and M. Pahor Diet-induced weight loss, exercise, and chronic inflammation in older, obese adults: a randomized controlled clinical trial Am. J. Clinical Nutrition, April 1, 2004; 79(4): 544 - 551. [Abstract] [Full Text] [PDF]
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T. You, D. M. Berman, A. S. Ryan, and B. J. Nicklas Effects of Hypocaloric Diet and Exercise Training on Inflammation and Adipocyte Lipolysis in Obese Postmenopausal Women J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1739 - 1746. [Abstract] [Full Text] [PDF]
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M. Mohlig, H. Boeing, J. Spranger, M. Osterhoff, A. Kroke, E. Fisher, M. M. Bergmann, M. Ristow, K. Hoffmann, and A. F. H. Pfeiffer Body Mass Index and C-174G Interleukin-6 Promoter Polymorphism Interact in Predicting Type 2 Diabetes J. Clin. Endocrinol. Metab., April 1, 2004; 89(4): 1885 - 1890. [Abstract] [Full Text] [PDF]
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P. A. Kern, G. Di Gregorio, T. Lu, N. Rassouli, and G. Ranganathan Perilipin Expression in Human Adipose Tissue Is Elevated with Obesity J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1352 - 1358. [Abstract] [Full Text] [PDF]
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A. G. Pittas, N. A. Joseph, and A. S. Greenberg Adipocytokines and Insulin Resistance J. Clin. Endocrinol. Metab., February 1, 2004; 89(2): 447 - 452. [Full Text] [PDF]
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P. Ferre The Biology of Peroxisome Proliferator-Activated Receptors: Relationship With Lipid Metabolism and Insulin Sensitivity Diabetes, February 1, 2004; 53(90001): S43 - 50. [Abstract] [Full Text]
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J. M. Bruun, A. S. Lihn, A. K. Madan, S. B. Pedersen, K. M. Schiott, J. N. Fain, and B. Richelsen Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue Am J Physiol Endocrinol Metab, January 1, 2004; 286(1): E8 - E13. [Abstract] [Full Text]
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A. S. Lihn, B. Richelsen, S. B. Pedersen, S. B. Haugaard, G. S. Rathje, S. Madsbad, and O. Andersen Increased expression of TNF-{alpha}, IL-6, and IL-8 in HALS: implications for reduced adiponectin expression and plasma levels Am J Physiol Endocrinol Metab, November 1, 2003; 285(5): E1072 - E1080. [Abstract] [Full Text] [PDF]
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L. K Heilbronn and E. Ravussin Calorie restriction and aging: review of the literature and implications for studies in humans Am. J. Clinical Nutrition, September 1, 2003; 78(3): 361 - 369. [Abstract] [Full Text] [PDF]
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K. Stenlof, I. Wernstedt, T. Fjallman, V. Wallenius, K. Wallenius, and J.-O. Jansson Interleukin-6 Levels in the Central Nervous System Are Negatively Correlated with Fat Mass in Overweight/Obese Subjects J. Clin. Endocrinol. Metab., September 1, 2003; 88(9): 4379 - 4383. [Abstract] [Full Text] [PDF]
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A. Steensberg, C. P. Fischer, C. Keller, K. Moller, and B. K. Pedersen IL-6 enhances plasma IL-1ra, IL-10, and cortisol in humans Am J Physiol Endocrinol Metab, August 1, 2003; 285(2): E433 - E437. [Abstract] [Full Text] [PDF]
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J. M. Fernandez-Real and W. Ricart Insulin Resistance and Chronic Cardiovascular Inflammatory Syndrome Endocr. Rev., June 1, 2003; 24(3): 278 - 301. [Abstract] [Full Text] [PDF]
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H.P. Kopp, C.W. Kopp, A. Festa, K. Krzyzanowska, S. Kriwanek, E. Minar, R. Roka, and G. Schernthaner Impact of Weight Loss on Inflammatory Proteins and Their Association With the Insulin Resistance Syndrome in Morbidly Obese Patients Arterioscler Thromb Vasc Biol, June 1, 2003; 23(6): 1042 - 1047. [Abstract] [Full Text] [PDF]
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J. J. Senn, P. J. Klover, I. A. Nowak, T. A. Zimmers, L. G. Koniaris, R. W. Furlanetto, and R. A. Mooney Suppressor of Cytokine Signaling-3 (SOCS-3), a Potential Mediator of Interleukin-6-dependent Insulin Resistance in Hepatocytes J. Biol. Chem., April 11, 2003; 278(16): 13740 - 13746. [Abstract] [Full Text] [PDF]
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K. Esposito, A. Pontillo, C. Di Palo, G. Giugliano, M. Masella, R. Marfella, and D. Giugliano Effect of Weight Loss and Lifestyle Changes on Vascular Inflammatory Markers in Obese Women: A Randomized Trial JAMA, April 9, 2003; 289(14): 1799 - 1804. [Abstract] [Full Text] [PDF]
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 G. G. L. Biondi-Zoccai, A. Abbate, G. Liuzzo, and L. M. Biasucci Atherothrombosis, inflammation, and diabetes J. Am. Coll. Cardiol., April 2, 2003; 41(7): 1071 - 1077. [Abstract] [Full Text] [PDF]
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K. Esposito, A. Pontillo, F. Giugliano, G. Giugliano, R. Marfella, G. Nicoletti, and D. Giugliano Association of Low Interleukin-10 Levels with the Metabolic Syndrome in Obese Women J. Clin. Endocrinol. Metab., March 1, 2003; 88(3): 1055 - 1058. [Abstract] [Full Text] [PDF]
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 N. Sattar, C. G Perry, and J. R Petrie Type 2 diabetes as an inflammatory disorder The British Journal of Diabetes & Vascular Disease, January 1, 2003; 3(1): 36 - 41. [Abstract] [PDF]
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 U. N. Das Is Metabolic Syndrome X an Inflammatory Condition? Experimental Biology and Medicine, December 1, 2002; 227(11): 989 - 997. [Abstract] [Full Text]
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 D. Lyngso, L. Simonsen, and J. Bulow Interleukin-6 production in human subcutaneous abdominal adipose tissue: the effect of exercise J. Physiol., August 15, 2002; 543(1): 373 - 378. [Abstract] [Full Text] [PDF]
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K. Esposito, A. Pontillo, M. Ciotola, C. Di Palo, E. Grella, G. Nicoletti, and D. Giugliano Weight Loss Reduces Interleukin-18 Levels in Obese Women J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3864 - 3866. [Abstract] [Full Text] [PDF]
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B. Peral, J. L. San Millan, R. Castello, P. Moghetti, and H. F. Escobar-Morreale The Methionine 196 Arginine Polymorphism in Exon 6 of the TNF Receptor 2 Gene (TNFRSF1B) Is Associated with the Polycystic Ovary Syndrome and Hyperandrogenism J. Clin. Endocrinol. Metab., August 1, 2002; 87(8): 3977 - 3983. [Abstract] [Full Text] [PDF]
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J.-P. Bastard, M. Maachi, J. T. van Nhieu, C. Jardel, E. Bruckert, A. Grimaldi, J.-J. Robert, J. Capeau, and B. Hainque Adipose Tissue IL-6 Content Correlates with Resistance to Insulin Activation of Glucose Uptake both in Vivo and in Vitro J. Clin. Endocrinol. Metab., May 1, 2002; 87(5): 2084 - 2089. [Abstract] [Full Text] [PDF]
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 M. Visser, M. Pahor, D. R. Taaffe, B. H. Goodpaster, E. M. Simonsick, A. B. Newman, M. Nevitt, and T. B. Harris Relationship of Interleukin-6 and Tumor Necrosis Factor-{alpha} With Muscle Mass and Muscle Strength in Elderly Men and Women: The Health ABC Study J. Gerontol. A Biol. Sci. Med. Sci., May 1, 2002; 57(5): M326 - 332. [Abstract] [Full Text]
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G. Villuendas, J. L. San Millan, J. Sancho, and H. F. Escobar-Morreale The -597 G->A and -174 G->C Polymorphisms in the Promoter of the IL-6 Gene Are Associated with Hyperandrogenism J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1134 - 1141. [Abstract] [Full Text] [PDF]
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C. A. Meier, E. Bobbioni, C. Gabay, F. Assimacopoulos-Jeannet, A. Golay, and J.-M. Dayer IL-1 Receptor Antagonist Serum Levels Are Increased in Human Obesity: A Possible Link to the Resistance to Leptin? J. Clin. Endocrinol. Metab., March 1, 2002; 87(3): 1184 - 1188. [Abstract] [Full Text] [PDF]
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A. Tchernof, A. Nolan, C. K. Sites, P. A. Ades, and E. T. Poehlman Weight Loss Reduces C-Reactive Protein Levels in Obese Postmenopausal Women Circulation, February 5, 2002; 105(5): 564 - 569. [Abstract] [Full Text] [PDF]
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J. Pfeilschifter, R. Koditz, M. Pfohl, and H. Schatz Changes in Proinflammatory Cytokine Activity after Menopause Endocr. Rev., February 1, 2002; 23(1): 90 - 119. [Abstract] [Full Text] [PDF]
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C. Perry, N. Sattar, and J. Petrie Review: Adipose tissue: passive sump or active pump? The British Journal of Diabetes & Vascular Disease, November 1, 2001; 1(2): 110 - 114. [Abstract] [PDF]
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