scholarly journals Release of Inflammatory Mediators by Human Adipose Tissue Is Enhanced in Obesity and Primarily by the Nonfat Cells: A Review

2010 ◽  
Vol 2010 ◽  
pp. 1-20 ◽  
Author(s):  
John N. Fain
Keyword(s):  
Adipose Tissue ◽  
In Vitro Release ◽  
Human Adipose Tissue ◽  
Fat Cells ◽  
Omental Adipose Tissue ◽  
Subcutaneous Adipose ◽  
Circulating Levels ◽  
Pai 1

This paper considers the role of putative adipokines that might be involved in the enhanced inflammatory response of human adipose tissue seen in obesity. Inflammatory adipokines [IL-6, IL-10, ACE, TGFβ1, TNFα, IL-1β, PAI-1, and IL-8] plus one anti-inflammatory [IL-10] adipokine were identified whose circulating levels as well as in vitro release by fat are enhanced in obesity and are primarily released by the nonfat cells of human adipose tissue. In contrast, the circulating levels of leptin and FABP-4 are also enhanced in obesity and they are primarily released by fat cells of human adipose tissue. The relative expression of adipokines and other proteins in human omental as compared to subcutaneous adipose tissue as well as their expression in the nonfat as compared to the fat cells of human omental adipose tissue is also reviewed. The conclusion is that the release of many inflammatory adipokines by adipose tissue is enhanced in obese humans.

Higher production of IL-8 in visceral vs. subcutaneous adipose tissue. Implication of nonadipose cells in adipose tissue

2004 ◽  
Vol 286 (1) ◽  
pp. E8-E13 ◽  
Author(s):  
Jens M. Bruun ◽  
Aina S. Lihn ◽  
Atul K. Madan ◽  
Steen B. Pedersen ◽  
Kirsten M. Schiøtt ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Human Adipose Tissue ◽  
Resistance Development ◽  
Paired Samples ◽  
Obese Subjects ◽  
Isolated Adipocytes ◽  
Subcutaneous Adipose ◽  
Circulating Levels

IL-8 is released from human adipose tissue. Circulating IL-8 is increased in obese compared with lean subjects and is associated with measures of insulin resistance, development of atherosclerosis, and cardiovascular disease. We studied 1) the production and release of IL-8 in vitro from paired samples of subcutaneous (SAT) and visceral (VAT) adipose tissue and 2) the production of IL-8 from whole adipose tissue, isolated adipocytes, and nonfat cells of adipose tissue. IL-8 release from VAT was fourfold higher than from SAT ( P < 0.05), and IL-8 mRNA was twofold higher in VAT compared with SAT ( P < 0.01). Dexamethasone (50 nM) attenuated IL-8 production by 50% ( P < 0.05), and IL-1β (2 μg/l) increased IL-8 production up to 15-fold ( P < 0.001). IL-8 release from whole SAT explants correlated with body mass index (BMI; r = 0.78; P < 0.001), as did IL-8 release from nonfat cells ( r = 0.79; P < 0.001). However, no correlation was found between IL-8 release from the fraction of isolated adipocytes and BMI ( r = 0.01). In conclusion, we demonstrated an increased release of IL-8 from VAT compared with SAT. Furthermore, our data suggest that the observed elevation in circulating levels of IL-8 in obese subjects is due primarily to the release of IL-8 from nonfat cells from adipose tissue. The high levels of IL-8 release from human adipose tissue and accumulation of this tissue in obese subjects may account for some of the increase in circulating IL-8 observed in obesity.

scholarly journals RANTES release by human adipose tissue in vivo and evidence for depot-specific differences

2009 ◽  
Vol 296 (6) ◽  
pp. E1262-E1268 ◽  
Author(s):  
Rana Madani ◽  
Kalypso Karastergiou ◽  
Nicola C. Ogston ◽  
Nazar Miheisi ◽  
Rahul Bhome ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Epicardial Adipose Tissue ◽  
Ex Vivo ◽  
Human Adipose Tissue ◽  
Fat Pad ◽  
Obese Subjects ◽  
Subcutaneous Adipose ◽  
Circulating Levels

Obesity is associated with elevated inflammatory signals from various adipose tissue depots. This study aimed to evaluate release of regulated on activation, normal T cell expressed and secreted (RANTES) by human adipose tissue in vivo and ex vivo, in reference to monocyte chemoattractant protein-1 (MCP-1) and interleukin-6 (IL-6) release. Arteriovenous differences of RANTES, MCP-1, and IL-6 were studied in vivo across the abdominal subcutaneous adipose tissue in healthy Caucasian subjects with a wide range of adiposity. Systemic levels and ex vivo RANTES release were studied in abdominal subcutaneous, gastric fat pad, and omental adipose tissue from morbidly obese bariatric surgery patients and in thoracic subcutaneous and epicardial adipose tissue from cardiac surgery patients without coronary artery disease. Arteriovenous studies confirmed in vivo RANTES and IL-6 release in adipose tissue of lean and obese subjects and release of MCP-1 in obesity. However, in vivo release of MCP-1 and RANTES, but not IL-6, was lower than circulating levels. Ex vivo release of RANTES was greater from the gastric fat pad compared with omental ( P = 0.01) and subcutaneous ( P = 0.001) tissue. Epicardial adipose tissue released less RANTES than thoracic subcutaneous adipose tissue in lean ( P = 0.04) but not obese subjects. Indexes of obesity correlated with epicardial RANTES but not with systemic RANTES or its release from other depots. In conclusion, RANTES is released by human subcutaneous adipose tissue in vivo and in varying amounts by other depots ex vivo. While it appears unlikely that the adipose organ contributes significantly to circulating levels, local implications of this chemokine deserve further investigation.

Additive effects of cortisol and growth hormone on regional and systemic lipolysis in humans

2004 ◽  
Vol 286 (3) ◽  
pp. E488-E494 ◽  
Author(s):  
C. B. Djurhuus ◽  
C. H. Gravholt ◽  
S. Nielsen ◽  
S. B. Pedersen ◽  
N. Møller ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Vastus Lateralis ◽  
Vastus Lateralis Muscle ◽  
Additive Effects ◽  
Subcutaneous Adipose ◽  
In Vivo Effects ◽  
Circulating Levels

Growth hormone (GH) and cortisol are important to ensure energy supplies during fasting and stress. In vitro experiments have raised the question whether GH and cortisol mutually potentiate lipolysis. In the present study, combined in vivo effects of GH and cortisol on adipose and muscle tissue were explored. Seven lean males were examined four times over 510 min. Microdialysis catheters were inserted in the vastus lateralis muscle and in the subcutaneous adipose tissue of the thigh and abdomen. A pancreatic-pituitary clamp was maintained with somatostatin infusion and replacement of GH, insulin, and glucagon at baseline levels. At t = 150 min, administration was performed of NaCl (I), a 2 μg·kg-1·min-1hydrocortisone infusion (II), a 200-μg bolus of GH (III), or a combination of II and III (IV). Systemic free fatty acid (FFA) turnover was estimated by [9,10-3H]palmitate appearance. Circulating levels of glucose, insulin, and glucagon were comparable in I-IV. GH levels were similar in I and II (0.50 ± 0.08 μg/l, mean ± SE). Peak levels during III and IV were ∼9 μg/l. Cortisol levels rose to ∼900 nmol/l in II and IV. Systemic (i.e., palmitate fluxes, s-FFA, s-glycerol) and regional (interstitial adipose tissue and skeletal muscle) markers of lipolysis increased in response to both II and III. In IV, they were higher and equal to the isolated additive effects of the two hormones. In conclusion, we find that GH and cortisol stimulate systemic and regional lipolysis independently and in an additive manner when coadministered. On the basis of previous studies, we speculate that the mode of action is mediated though different pathways.

scholarly journals TSH stimulates leptin secretion by a direct effect on adipocytes

2003 ◽  
Vol 176 (1) ◽  
pp. 7-12 ◽  
Author(s):  
C Menendez ◽  
R Baldelli ◽  
JP Camina ◽  
B Escudero ◽  
R Peino ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Homeostasis ◽  
Direct Action ◽  
Human Adipose Tissue ◽  
Pituitary Hormones ◽  
Organ Cultures ◽  
Omental Adipose Tissue ◽  
Thyroid Axis ◽  
The Central Nervous System

Leptin is a circulating hormone secreted by adipose tIssue which acts as a signal to the central nervous system where it regulates energy homeostasis and neuroendocrine processes. Although leptin modulates the secretion of several pituitary hormones, no information is available regarding a direct action of pituitary products on leptin release. However, it has been pointed out that leptin and TSH have a coordinated pulsatility in plasma. In order to test a direct action of TSH on in vitro leptin secretion, a systematic study of organ cultures of human omental adipose tIssue was performed in samples obtained at surgery from 34 patients of both sexes during elective abdominal surgery. TSH powerfully stimulated leptin secretion by human adipose tIssue in vitro. In contrast, prolactin, ACTH, FSH and LH were devoid of action. These results suggest that leptin and the thyroid axis maintain a complex and dual relationship and open the possibility that plasmatic changes in TSH may contribute to the regulation of leptin pulses.

scholarly journals Retinoic acid and vitamin D(3) powerfully inhibit in vitro leptin secretion by human adipose tissue

2001 ◽  
Vol 170 (2) ◽  
pp. 425-431 ◽  
Author(s):  
C Menendez ◽  
M Lage ◽  
R Peino ◽  
R Baldelli ◽  
P Concheiro ◽  
...  
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Retinoic Acid ◽  
Energy Homeostasis ◽  
Human Adipose Tissue ◽  
Tissue Samples ◽  
Omental Adipose Tissue ◽  
Vitamin D 3 ◽  
Gender Based

Leptin, the product of the ob gene, is secreted into the circulation by white adipose tissue; its major role being to participate in the regulation of energy homeostasis. Plasma leptin levels are mainly determined by the relative adiposity of the subject; however, the great dispersion of values for any given body mass index and the noteworthy gender-based differences indicate that other factors are operating. Steroid hormones actively participate in the regulation of leptin secretion; however, non-steroid nuclear hormones have either not been studied or have provided contradictory results. In order to understand the role of hormones of the non-steroid superfamily such as 3,5,3'-tri-iodothyronine (T(3)), vitamin D(3) and retinoic acid (RA) in the control of leptin secretion, in the present work doses of 10(-9), 10(-8) and 10(-7) M of these compounds have been studied on in vitro leptin secretion. The organ culture was performed with omental adipose tissue samples from healthy donors (n=28). T(3) was devoid of effect at any dose studied, while an inhibition of leptin secretion was observed with 9-cis-RA (slight) and all-trans-RA (potent). Interestingly, vitamin D(3) exerted a powerfully inhibitory role at the doses studied, and its action was synergistic with all-trans-RA. In conclusion, in vitro leptin secretion by human adipose tissue is negatively controlled by either RA or vitamin D(3). The clinical significance of leptin regulation by this superfamily of nuclear receptors remains to be ascertained.

Reduced glucose incorporation to triglycerides following chronic exposure of human fat cells to growth hormone

1980 ◽  
Vol 95 (1) ◽  
pp. 129-133 ◽  
Author(s):  
Gudrun Nyberg ◽  
Stig Boström ◽  
Rolf Johansson ◽  
Ulf Smith
Keyword(s):  
Growth Hormone ◽  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Human Growth ◽  
Human Adipose Tissue ◽  
Culture Technique ◽  
Fat Cells ◽  
Glucose Incorporation ◽  
Total Glucose

Abstract. Using the tissue culture technique we have recently demonstrated that long-term exposure of human adipose tissue to human growth hormone (GH) in vitro leads to an impairment in glucose incorporation into triglycerides. This effect was further studied in the present investigation. Biopsies of human adipose tissue which had been cultured for one week with or without GH were studied in subsequent short-term incubations where the conversion of glucose to CO2 and to total lipids was determined. The formation of CO2 was not changed by previous exposure of the biopsies to GH whereas the incorporation of glucose into triglycerides was reduced by about one third. Total glucose metabolism, as determined from the sum of the two pathways, was significantly reduced. The activities of three glycolytic enzymes were determined in biopsies of human adipose tissue which had been cultured with or without GH for one week. The activity of phosphofructokinase was reduced, while the hexokinase and the glucose-6-phosphate dehydrogenase activities were unchanged. The diminished activity of phosphofructokinase, the enzyme considered to be rate-limiting for glycolysis in human fat cells, may be responsible for the decreased rate of glucose metabolism found.

Stimulation of PAI-1 and adipokines by glucose in human adipose tissue in vitro

2003 ◽  
Vol 310 (3) ◽  
pp. 878-883 ◽  
Author(s):  
G. He ◽  
J.M. Bruun ◽  
A.S. Lihn ◽  
S.B. Pedersen ◽  
B. Richelsen
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Adipose Tissue In Vitro ◽  
Pai 1 ◽  
Stimulation Of

scholarly journals Integrative mRNA-microRNA analyses reveal novel interactions related to insulin sensitivity in human adipose tissue

2016 ◽  
Vol 48 (2) ◽  
pp. 145-153 ◽  
Author(s):  
Tyler J. Kirby ◽  
R. Grace Walton ◽  
Brian Finlin ◽  
Beibei Zhu ◽  
Resat Unal ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Human Adipose Tissue ◽  
Whole Body ◽  
Insulin Resistant ◽  
Novel Interactions ◽  
Subcutaneous Adipose ◽  
The Relationship ◽  
Microrna Microarray

Adipose tissue has profound effects on whole-body insulin sensitivity. However, the underlying biological processes are quite complex and likely multifactorial. For instance, the adipose transcriptome is posttranscriptionally modulated by microRNAs, but the relationship between microRNAs and insulin sensitivity in humans remains to be determined. To this end, we utilized an integrative mRNA-microRNA microarray approach to identify putative molecular interactions that regulate the transcriptome in subcutaneous adipose tissue of insulin-sensitive (IS) and insulin-resistant (IR) individuals. Using the NanoString nCounter Human v1 microRNA Expression Assay, we show that 17 microRNAs are differentially expressed in IR vs. IS. Of these, 16 microRNAs (94%) are downregulated in IR vs. IS, including miR-26b, miR-30b, and miR-145. Using Agilent Human Whole Genome arrays, we identified genes that were predicted targets of miR-26b, miR-30b, and miR-145 and were upregulated in IR subjects. This analysis produced ADAM22, MYO5A, LOX, and GM2A as predicted gene targets of these microRNAs. We then validated that miR-145 and miR-30b regulate these mRNAs in differentiated human adipose stem cells. We suggest that use of bioinformatic integration of mRNA and microRNA arrays yields verifiable mRNA-microRNA pairs that are associated with insulin resistance and can be validated in vitro.

scholarly journals The color of fat and its central role in the development and progression of metabolic diseases

2017 ◽  
Vol 31 (1) ◽  
Author(s):  
Melania Gaggini ◽  
Fabrizia Carli ◽  
Amalia Gastaldelli
Keyword(s):  
Adipose Tissue ◽  
Glucose Metabolism ◽  
Subcutaneous Adipose Tissue ◽  
Metabolic Diseases ◽  
Caloric Intake ◽  
Human Adipose Tissue ◽  
Normal Weight ◽  
Metabolic Characteristics ◽  
Subcutaneous Adipose

AbstractExcess caloric intake does not always translate to an expansion of the subcutaneous adipose tissue (SAT) and increase in fat mass. It is now recognized that adipocyte type (white, WAT, or brown, BAT), size (large vs. small) and metabolism are important factors for the development of cardiometabolic diseases. When the subcutaneous adipose tissue is not able to expand in response to increased energy intake the excess substrate is stored as visceral adipose tissue or as ectopic fat in tissues as muscle, liver and pancreas. Moreover, adipocytes become dysfunctional (adiposopathy, or sick fat), adipokines secretion is increased, fat accumulates in ectopic sites like muscle and liver and alters insulin signaling, increasing the demand for insulin secretion. Thus, there are some subjects that despite having normal weight have the metabolic characteristics of the obese (NWMO), while some obese expand their SAT and remain metabolically healthy (MHO). In this paper we have reviewed the recent findings that relate the metabolism of adipose tissue and its composition to metabolic diseases. In particular, we have discussed the possible role of dysfunctional adipocytes and adipose tissue resistance to the antilipolytic effect of insulin on the development of impaired glucose metabolism. Finally we have reviewed the possible role of BAT vs. WAT in the alteration of lipid and glucose metabolism and the recent studies that have tried to stimulate browning in human adipose tissue.

In vitro lipid synthesis in human adipose tissue from three abdominal sites

1993 ◽  
Vol 265 (3) ◽  
pp. E374-E379 ◽  
Author(s):  
N. K. Edens ◽  
S. K. Fried ◽  
J. G. Kral ◽  
J. Hirsch ◽  
R. L. Leibel
Keyword(s):  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Lipid Synthesis ◽  
Human Adipose Tissue ◽  
Obese Women ◽  
Cellular Mechanisms ◽  
Severely Obese ◽  
Fatty Acid Release ◽  
Subcutaneous Adipose

The association between abdominal deposition of adipose tissue and morbidities accompanying obesity may be related to high rates of free fatty acid release from enlarged intra-abdominal stores. To investigate cellular mechanisms that might contribute to enlargement of intra-abdominal adipocytes, lipolysis, triacylglycerol (TG), and diacylglycerol (DG) synthesis from [14C]glucose was measured in abdominal subcutaneous, omental, and mesenteric adipose tissue from severely obese women and men. Subcutaneous adipose tissue from women showed the highest rates of TG synthesis compared with the intra-abdominal site, or any site in men. isoproterenol stimulated TG synthesis more in intra-abdominal than subcutaneous adipose tissue. In the basal state, intra-abdominal adipose tissue from both men and women showed rates of [14C]DG accumulation approximately 50% total [14C]acylglyceride accumulation, whereas, in subcutaneous adipose tissue, [14C]DG accumulation was approximately 25% of total. Basal lipolysis was lower in intra-abdominal than subcutaneous adipocytes. Stimulation of lipolysis reduced [14C]DG accumulation more in intra-abdominal than subcutaneous adipose tissue. Low rates of acylglyceride synthesis in intra-abdominal adipocytes may prevent accumulation of large intra-abdominal fat stores in women.

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