Adipose tissue production of hepatocyte growth factor contributes to elevated serum HGF in obesity

2006 ◽  
Vol 291 (4) ◽  
pp. E843-E848 ◽  
Author(s):  
Lauren N. Bell ◽  
Jennifer L. Ward ◽  
Mikako Degawa-Yamauchi ◽  
Jason E. Bovenkerk ◽  
RoseMarie Jones ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Elevated Serum ◽  
Mrna Levels ◽  
Tissue Mass ◽  
Tnf Α ◽  
Before And After ◽  
Obese Subjects ◽  
Hepatocyte Growth

Serum HGF is elevated in obese individuals. This study examined the contribution of excess adipose tissue to increased circulating HGF levels in obesity. Serum HGF was measured by ELISA before and after weight loss due to bariatric surgery or a 24-h fast. At 6.1 ± 0.1 mo following surgery, BMI (50.6 ± 1.6 vs. 35.1 ± 1.3 kg/m2; P < 0.0001) and serum HGF were significantly decreased (1,164 ± 116 vs. 529 ± 39 pg/ml, P < 0.001). A 24-h fast did not change serum HGF, but serum leptin was significantly reduced (67.7 ± 7.1 vs. 50.3 ± 8.3 ng/ml, P = 0.02). HGF secretion in vitro from adipocytes of obese (BMI 40.3 ± 2.8 kg/m2) subjects was significantly greater (80.9 ± 10.4 vs. 21.5 ± 4.0 pg/105 cells, P = 0.008) than release from adipocytes of lean (BMI 23.3 ± 1.4 kg/m2) subjects. HGF mRNA levels determined by real-time RT-PCR were not different in adipocytes from lean (BMI 24.0 ± 0.8 kg/m2) and obese (45.7 ± 3.0 kg/m2) subjects, but serum HGF was significantly elevated in the obese individuals studied (787 ± 61 vs. 489 ± 49 pg/ml, P = 0.001). TNF-α (24 h treatment) significantly increased HGF release from subcutaneous adipocytes 23.6 ± 8.3% over control ( P = 0.02). These data suggest that elevated serum HGF in obesity is in part attributable to excess adipose tissue and that this effect can be reversed by reducing adipose tissue mass through weight loss. Increased HGF secretion from adipocytes of obese subjects may be due to posttranscriptional events possibly related to adipocyte size and stimulation by elevated TNF-α in the adipose tissue of obese individuals.

Regulation of adiponectin by adipose tissue-derived cytokines: in vivo and in vitro investigations in humans

2003 ◽  
Vol 285 (3) ◽  
pp. E527-E533 ◽  
Author(s):  
Jens M. Bruun ◽  
Aina S. Lihn ◽  
Camilla Verdich ◽  
Steen B. Pedersen ◽  
Søren Toubro ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Mrna Levels ◽  
Plasma Adiponectin ◽  
Tnf Α ◽  
Adiponectin Mrna ◽  
Before And After

Adiponectin is an adipose tissue-specific protein that is abundantly present in the circulation and suggested to be involved in insulin sensitivity and development of atherosclerosis. Because cytokines are suggested to regulate adiponectin, the aim of the present study was to investigate the interaction between adiponectin and three adipose tissue-derived cytokines (IL-6, IL-8, and TNF-α). The study was divided into three substudies as follows: 1) plasma adiponectin and mRNA levels in adipose tissue biopsies from obese subjects [mean body mass index (BMI): 39.7 kg/m2, n = 6] before and after weight loss; 2) plasma adiponectin in obese men (mean BMI: 38.7 kg/m2, n = 19) compared with lean men (mean BMI: 23.4 kg/m2, n = 10) before and after weight loss; and 3) in vitro direct effects of IL-6, IL-8, and TNF-α on adiponectin mRNA levels in adipose tissue cultures. The results were that 1) weight loss resulted in a 51% ( P < 0.05) increase in plasma adiponectin and a 45% ( P < 0.05) increase in adipose tissue mRNA levels; 2) plasma adiponectin was 53% ( P < 0.01) higher in lean compared with obese men, and plasma adiponectin was inversely correlated with adiposity, insulin sensitivity, and IL-6; and 3) TNF-α ( P < 0.01) and IL-6 plus its soluble receptor ( P < 0.05) decreased adiponectin mRNA levels in vitro. The inverse relationship between plasma adiponectin and cytokines in vivo and the cytokine-induced reduction in adiponectin mRNA in vitro suggests that endogenous cytokines may inhibit adiponectin. This could be of importance for the association between cytokines (e.g., IL-6) and insulin resistance and atherosclerosis.

scholarly journals Increased adiponectin receptor-1 expression in adipose tissue of impaired glucose-tolerant obese subjects during weight loss

2006 ◽  
Vol 155 (1) ◽  
pp. 161-165 ◽  
Author(s):  
M J Kim ◽  
M Maachi ◽  
C Debard ◽  
E Loizon ◽  
K Clément ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Metabolic Parameters ◽  
Peroxisome Proliferator ◽  
Mrna Levels ◽  
Very Low Calorie Diet ◽  
Peroxisome Proliferator Activated Receptor ◽  
Before And After ◽  
Obese Subjects

Objective: To investigate the mRNA expression of adiponectin, AdipoR1 and AdipoR2, the two recently cloned adiponectin receptors and peroxisome proliferator activated receptor (PPAR)γ2 in adipose tissue of obese individuals before and during a very low calorie diet (VLCD) inducing weight loss. Methods: Twenty-three non-diabetic obese subjects with normal (NGT, n=11) or impaired glucose tolerance (IGT, n=12) (age, 47±3 years; body mass index, 39.3±1.3 kg/m2) were studied before and after a 3-week 3.9 MJ diet daily without exercise. mRNA levels of nine IGT and six NGT subjects were measured by real-time PCR in s.c. abdominal adipose tissue. Results: Metabolic parameters and insulin sensitivity were improved by VLCD in the IGT group, but minimally affected in the NGT group. VLCD increased expression of AdipoR1 in the IGT (P=0.02), but not in the NGT group. Adiponectin, AdipoR2 and PPARγ2 mRNA levels did not change during VLCD in any group. In the IGT, but not in the NGT group, AdipoR1 and AdipoR2 expressions were positively related to that of PPARγ2 and, after VLCD, AdipoR1 and AdipoR2 expressions were positively related to each other and to that of adiponectin. Conclusion: In the NGT group, the 3-week VLCD inducing weight loss did not modify metabolic parameters, insulin sensitivity and the expression of the adiponectin system in adipose tissue. By contrast, in the IGT group, AdipoR1 expression increased and we found a coordinate regulation of the expression of adiponectin and its receptors. These modifications could participate, through adiponectin action on adipocytes, to the improved metabolic parameters observed in IGT subjects.

scholarly journals Effect of hypocaloric diet-induced weight loss in obese women on plasma apelin and adipose tissue expression of apelin and APJ.

2008 ◽  
Vol 158 (6) ◽  
pp. 905-910 ◽  
Author(s):  
Isabelle Castan-Laurell ◽  
Michaela Vítkova ◽  
Danièle Daviaud ◽  
Cédric Dray ◽  
Michaela Kováčiková ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Plasma Levels ◽  
Tissue Expression ◽  
Hypocaloric Diet ◽  
Mrna Levels ◽  
Obese Women ◽  
Tnf Α ◽  
Before And After ◽  
Plasma Apelin

ObjectiveApelin is a novel adipokine acting on APJ receptor, regulated by insulin and tumor necrosis factor-α (TNF-α) in adipose tissue (AT). Plasma apelin levels are increased in obese hyperinsulinemic subjects. The aim was to investigate whether the hypocaloric diet associated with weight loss modifies the elevated plasma apelin levels and the expression of apelin and APJ receptor in AT in obese women.Design and methodsFasting plasma levels of apelin and TNF-α as well as mRNA levels of apelin and APJ in AT were measured before and after a 12-week hypocaloric weight-reducing diet in 20 obese women (body mass index (BMI) before diet 32.2±6.4 kg/m2). Twelve healthy women with a BMI of 20.7±0.6 kg/m2 served as reference.ResultsPlasma levels of apelin and TNF-α were higher in obese compared with lean controls. The hypocaloric diet resulted in a significant decrease of BMI to 29.8±6.3 kg/m2, plasma insulin (8.16±0.73 to 6.58±0.66 mU/l), apelin (369±25 pg/ml to 257±12 pg/ml), TNF-α levels (0.66±0.04 pg/ml to 0.56±0.04 pg/ml), and AT mRNAs of apelin and APJ. In addition, changes in AT mRNA apelin were related to changes in AT mRNA APJ levels.ConclusionThe hypocaloric diet associated with weight loss reduces the increased plasma and AT expression of apelin in obese women. This reduced apelin expression in AT could contribute to decreased circulating apelin levels.

scholarly journals Decreased TLR3 in Hyperplastic Adipose Tissue, Blood and Inflamed Adipocytes is Related to Metabolic Inflammation

2018 ◽  
Vol 51 (3) ◽  
pp. 1051-1068 ◽  
Author(s):  
Jèssica Latorre ◽  
José M. Moreno-Navarrete ◽  
Mónica Sabater ◽  
Maria Buxo ◽  
José I. Rodriguez-Hermosa ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Low Grade ◽  
Metabolic Inflammation ◽  
Fat Depots ◽  
Acute Surgery ◽  
Obese Subjects ◽  
Anti Inflammatory ◽  
The Impact

Background/Aims: Obesity is characterized by the immune activation that eventually dampens insulin sensitivity and changes metabolism. This study explores the impact of different inflammatory/ anti-inflammatory paradigms on the expression of toll-like receptors (TLR) found in adipocyte cultures, adipose tissue, and blood. Methods: We evaluated by real time PCR the impact of acute surgery stress in vivo (adipose tissue) and macrophages (MCM) in vitro (adipocytes). Weight loss was chosen as an anti-inflammatory model, so TLR were analyzed in fat samples collected before and after bariatric surgery-induced weight loss. Associations with inflammatory and metabolic parameters were analyzed in non-obese and obese subjects, in parallel with gene expression measures taken in blood and isolated adipocytes/ stromal-vascular cells (SVC). Treatments with an agonist of TLR3 were conducted in human adipocyte cultures under normal conditions and upon conditions that simulated the chronic low-grade inflammatory state of obesity. Results: Surgery stress raised TLR1 and TLR8 in subcutaneous (SAT), and TLR2 in SAT and visceral (VAT) adipose tissue, while decreasing VAT TLR3 and TLR4. MCM led to increased TLR2 and diminished TLR3, TLR4, and TLR5 expressions in human adipocytes. The anti-inflammatory impact of weight loss was concomitant with decreased TLR1, TLR3, and TLR8 in SAT. Cross-sectional associations confirmed increased V/ SAT TLR1 and TLR8, and decreased TLR3 in obese patients, as compared with non-obese subjects. As expected, TLR were predominant in SVC and adipocyte precursor cells, even though expression of all of them but TLR8 (very low levels) was also found in ex vivo isolated and in vitro differentiated adipocytes. Among SVC, CD14+ macrophages showed increased TLR1, TLR2, and TLR7, but decreased TLR3 mRNA. The opposite patterns shown for TLR2 and TLR3 in V/ SAT, SVC, and inflamed adipocytes were observed in blood as well, being TLR3 more likely linked to lymphocyte instead of neutrophil counts. On the other hand, decreased TLR3 in adipocytes challenged with MCM dampened lipogenesis and the inflammatory response to Poly(I:C). Conclusion: Functional variations in the expression of TLR found in blood and hypertrophied fat depots, namely decreased TLR3 in lymphocytes and inflamed adipocytes, are linked to metabolic inflammation.

Secretion of neuropeptide Y in human adipose tissue and its role in maintenance of adipose tissue mass

2007 ◽  
Vol 293 (5) ◽  
pp. E1335-E1340 ◽  
Author(s):  
Katarina Kos ◽  
Alison L. Harte ◽  
Sean James ◽  
David R. Snead ◽  
Joseph P. O'Hare ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Protein Expression ◽  
Elective Surgery ◽  
Ex Vivo ◽  
Human Adipose Tissue ◽  
Tissue Mass ◽  
Paracrine Effects ◽  
Tnf Α ◽  
Adiposity Signals

NPY is an important central orexigenic hormone, but little is known about its peripheral actions in human adipose tissue (AT) or its potential paracrine effects. Our objective was to examine NPY's role in AT, specifically addressing NPY protein expression, the effect of NPY on adipokine secretion, and the influence of insulin and rosiglitazone (RSG) on adipocyte-derived NPY in vitro. Ex vivo human AT was obtained from women undergoing elective surgery [age: 42.7 ± 1.5 yr (mean ± SE), BMI: 26.2 ± 0.7 kg/m2; n = 38]. Western blot analysis was used to determine NPY protein expression in AT depots. Abdominal subcutaneous (AbSc) adipocytes were isolated and treated with recombinant (rh) NPY, insulin, and RSG. NPY and adipokine levels were measured by ELISA. Our results were that NPY was localized in human AT and adipocytes and confirmed by immunohistochemistry. Depot-specific NPY expression was noted as highest in AbSc AT (1.87 ± 0.23 ODU) compared with omental (Om; 1.03 ± 0.15 ODU, P = 0.029) or thigh AT (Th; 1.0 ± 0.29 ODU, P = 0.035). Insulin increased NPY secretion (control: 0.22 ± 0.024 ng/ml; 1 nM insulin: 0.26 ± 0.05 ng/ml; 100 nM insulin: 0.29 ± 0.04 ng/ml; 1,000 nM insulin: 0.3 ± 0.04 ng/ml; P < 0.05, n = 13), but cotreatment of RSG (10 nM) with insulin (100 nM) had no effect on NPY secretion. Furthermore, adipocyte treatment with rh-NPY downregulated leptin secretion (control: 6.99 ± 0.89 ng/ml; 1 nmol/l rh-NPY: 4.4 ± 0.64 ng/ml; 10 nmol/l rh-NPY: 4.3 ± 0.61 ng/ml, 100 nmol/l rh-NPY: 4.2 ± 0.67 ng/ml; P < 0.05, n = 10) but had no effect on adiponectin or TNF-α secretion. We conclude that NPY is expressed and secreted by human adipocytes. NPY secretion is stimulated by insulin, but this increment was limited by cotreatment with RSG. NPY's antilipolytic action may promote an increase in adipocyte size in hyperinsulinemic conditions. Adipose-derived NPY mediates reduction of leptin secretion and may have implications for central feedback of adiposity signals.

scholarly journals Lower Zinc-α2-Glycoprotein Production by Adipose Tissue and Liver in Obese Patients Unrelated to Insulin Resistance

2009 ◽  
Vol 94 (11) ◽  
pp. 4499-4507 ◽  
Author(s):  
David M. Selva ◽  
Albert Lecube ◽  
Cristina Hernández ◽  
Juan A. Baena ◽  
José M. Fort ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Mass Index ◽  
Adipose Tissue ◽  
Body Mass ◽  
Control Group ◽  
Mrna Levels ◽  
Model Assessment ◽  
Obese Patients ◽  
Obese Subjects

Context: Zinc-α2 glycoprotein (ZAG) has been proposed as a new candidate in the pathogenesis of obesity, but most of the information stems from studies performed in rodents and in vitro assays. Objective: The main aim of the study was to compare serum levels of ZAG and its expression (mRNA levels and protein) in adipose tissue and the liver between obese and nonobese subjects. The relationship between ZAG and insulin resistance was also explored. Design: This was a case-control study. Setting: The study was conducted at a university referral center. Patients and Methods: Samples of serum, sc adipose tissue (SAT), visceral adipose tissue (VAT), and liver were obtained from 20 obese subjects during bariatric surgery. Samples from 10 nonobese patients matched by age and gender were used as a control group. Serum ZAG levels were determined by ELISA. ZAG mRNA levels were measured by real-time PCR and protein content by Western blot. The effect of insulin on liver production of ZAG was assessed using HepG2 cultures. Results: Serum concentration of ZAG (micrograms per milliliter) was significantly lower in obese subjects (40.87 ± 10.45 vs. 63.26 ± 16.40; P = 0.002). ZAG expression was significantly lower in the adipose tissue (SAT and VAT) and liver of obese patients than in control subjects. Significant negative correlations between body mass index and circulating ZAG (r = −0.65, P &lt; 0.001) as well as between body mass index and mRNA ZAG levels in SAT (r = −0.68, P &lt; 0.001) and VAT were detected (r = −0.64, P &lt; 0.001). No relationship was found between ZAG and homeostasis model assessment for insulin resistance and insulin had no effect on ZAG production in vitro. Conclusion: A down-regulation of ZAG in SAT, VAT, and liver exists in obese patients but seems unrelated to insulin resistance. A downregulation of zinc-α2 glycoprotein in adipose tissue and liver exists in obese patients, and it is unrelated to insulin resistance.

Endurance training changes in lipolytic responsiveness of obese adipose tissue

1998 ◽  
Vol 275 (6) ◽  
pp. E951-E956 ◽  
Author(s):  
I. De Glisezinski ◽  
F. Crampes ◽  
I. Harant ◽  
M. Berlan ◽  
J. Hejnova ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Physical Training ◽  
The Body ◽  
Hormone Sensitive Lipase ◽  
Aerobic Exercise Training ◽  
Adrenoceptor Agonist ◽  
Before And After ◽  
Hormone Sensitive ◽  
Obese Subjects

The aim of this study was to investigate the effect of aerobic exercise training on the lipolytic response of adipose tissue in obese subjects. Thirteen men (body mass index = 36.9 ± 1.3 kg/m2) were submitted to aerobic physical training on a cycloergometer (30–45 min, 4 days a wk) for 3 mo. Adipocyte sensitivity to the action of catecholamines and insulin was studied in vitro before and after training. Training induced a decrease in the percentage of fat mass ( P < 0.05) without changing the body weight. Basal lipolysis and hormone-sensitive lipase activity were significantly decreased after training ( P < 0.05). The lipolytic effects of epinephrine, isoprenaline (β-adrenoceptor agonist), and dobutamine (β1-adrenoceptor agonist) were significantly increased ( P < 0.05) but not those of procaterol (β2-adrenoceptor agonist). The antilipolytic effects of α2-adrenoceptor and insulin were significantly decreased ( P < 0.05). Lipolysis stimulation by agents acting at the postreceptor level was unchanged after training. In conclusion, aerobic physical training in obese male subjects modifies adipose tissue lipolysis through an enhancement of β-adrenergic response and a concomitant blunting of adipocyte antilipolytic activity.

Change in β1-adrenergic receptor protein concentration in adipose tissue correlates with diet-induced weight loss

2005 ◽  
Vol 108 (4) ◽  
pp. 323-329 ◽  
Author(s):  
Mads RASMUSSEN ◽  
Anita BELZA ◽  
Thomas ALMDAL ◽  
Søren TOUBRO ◽  
Palle BRATHOLM ◽  
...  
Keyword(s):  
Weight Loss ◽  
Adipose Tissue ◽  
Adrenergic Receptor ◽  
Laser Scanning ◽  
Protein Concentration ◽  
Receptor Protein ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Β2 Adrenergic Receptor ◽  
Obese Subjects

The aim of the present study was to examine gene expression and protein concentrations of β1- and β2-adrenergic receptors in subcutaneous adipose tissue in obese subjects in response to weight loss. Eighteen obese subjects were studied during diet-induced weight loss. β-Adrenergic receptor mRNA levels were quantified by reverse transcription-PCR–HPLC. β-Adrenergic receptor protein concentrations were measured by Western blotting using fluorescence laser scanning for detection. Subjects lost 12.8±0.8 kg (mean±S.E.M.) during diet treatment. There was a 34% decrease in the β1-adrenergic receptor mRNA level (0.92±0.09 compared with 0.61±0.06 amol/μg of DNA; P<0.002). β2-Adrenergic receptor mRNA did not decrease significantly. β2-Adrenergic receptor protein concentration decreased 37% (25.5±7.1 compared with 16.0±5.6 arbitrary units/ng of DNA; P=0.008), whereas β1-adrenergic receptor protein concentration did not decrease significantly. The degree of weight loss was correlated with the concentration of β1-adrenergic receptor protein (r=0.65, P<0.003) and changes in receptor protein concentration (r=0.50, P=0.035) during the very-low-calorie diet. In conclusion, the present study demonstrates a relationship between β1-adrenergic receptor protein concentration in adipose tissue and the degree of weight loss. This relationship is not directly related to energy expenditure and deserves further investigation.

Isoproterenol decreases leptin release from rat and human adipose tissue through posttranscriptional mechanisms

2005 ◽  
Vol 288 (4) ◽  
pp. E798-E804 ◽  
Author(s):  
Matthew R. Ricci ◽  
Mi-Jeong Lee ◽  
Colleen D. Russell ◽  
Yanxin Wang ◽  
Sean Sullivan ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Relative Rate ◽  
Human Adipose Tissue ◽  
Rapid Decline ◽  
Mrna Levels ◽  
Adrenergic Regulation ◽  
Obese Subjects ◽  
Rat Adipose Tissue

In vivo and in vitro studies indicate that β-adrenergic receptor agonists decrease leptin release from fat cells in as little as 30 min. Our objective was to determine whether alterations in leptin biosynthesis or secretion were involved in the short-term adrenergic regulation of leptin in human and rat adipose tissue. Isoproterenol (Iso) decreased leptin release from incubated adipose tissue of both nonobese and obese subjects to similar extent (−28 vs. −21% after 3 h). Inhibition of protein synthesis with cycloheximide did not block the effect of Iso on leptin release from human adipose tissue, suggesting that the Iso effect is independent of leptin synthesis. Iso also tended to increase tissue leptin content at the end of the 3-h incubation, as expected from the observed inhibition of release. Consistent with a posttranslational mechanism, Iso treatment did not affect leptin mRNA levels or relative rate of leptin biosynthesis as directly assessed by [35S]methionine incorporation into immunoprecipitable leptin. In contrast to these results in human adipose tissues, Iso did not decrease basal leptin release from rat adipose tissue. However, Iso did decrease insulin-stimulated leptin release by inhibiting the ability of insulin to increase leptin biosynthesis without detectably affecting leptin mRNA levels. Thus, in both human and rat, adrenergic regulation of posttranscriptional events (secretion in humans, translation in rats) may contribute to the rapid decline in circulating leptin that occurs when the sympathetic nervous system is activated, such as during fasting and cold exposure. Furthermore, the rat does not provide an ideal model to study mechanisms of cellular leptin regulation in humans.

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