Acute and chronic regulation of leptin synthesis, storage, and secretion by insulin and dexamethasone in human adipose tissue

2007 ◽  
Vol 292 (3) ◽  
pp. E858-E864 ◽  
Author(s):  
Mi-Jeong Lee ◽  
Yanxin Wang ◽  
Matthew R. Ricci ◽  
Sean Sullivan ◽  
Colleen D. Russell ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Acute Treatment ◽  
Human Adipose Tissue ◽  
Metabolic Labeling ◽  
Mrna Levels ◽  
Fat Cell ◽  
Short Term ◽  
Chronic Effects ◽  
Wide Range ◽  
Highly Correlated

Serum leptin levels are upregulated in proportion to body fat and also increase over the short term in response to meals or insulin. To understand the mechanisms involved, we assessed leptin synthesis and secretion in samples of adipose tissue from subjects with a wide range of BMI. Tissue leptin content and relative rates of leptin biosynthesis, as determined by metabolic labeling, were highly correlated with each other and with BMI and fat cell size. To understand mechanisms regulating leptin synthesis in obesity, we used biosynthetic labeling to directly assess the effects of insulin and glucocorticoids (dexamethasone) on leptin synthesis and secretion in human adipose tissue. Chronic treatment (1–2 days in organ culture) with insulin increased relative rates of leptin biosynthesis without affecting leptin mRNA levels. In contrast, dexamethasone increased leptin mRNA and biosynthesis in parallel. Acute treatment with insulin or dexamethasone (added during 1-h preincubation and 45-min pulse labeling) did not affect relative rates of leptin biosynthesis, but pulse-chase studies showed that addition of insulin nearly doubled the release of [35S]leptin after a 1-h chase. We conclude that the higher leptin stores in adipose tissue of obese humans are maintained by chronic effects of insulin and glucocorticoids acting at pre- and posttranslational levels and that the ability of insulin to increase the release of preformed leptin may contribute to short-term variations in circulating leptin levels.

scholarly journals Human Adipose Tissue Cannabinoid Receptor 1 Gene Expression Is Not Related to Fat Cell Function or Adiponectin Level

2007 ◽  
Vol 92 (4) ◽  
pp. 1555-1559 ◽  
Author(s):  
Patrik Löfgren ◽  
Eva Sjölin ◽  
Kerstin Wåhlen ◽  
Johan Hoffstedt
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Cell Function ◽  
Cannabinoid Receptor ◽  
Human Adipose Tissue ◽  
Mrna Levels ◽  
Fat Cell ◽  
Cannabinoid Receptor 1 ◽  
Omental Fat ◽  
Cnr1 Gene

Abstract Context: The cannabinoid receptor 1 gene (CNR1) is implicated in adipocyte function. Objective: We investigated human adipose tissue CNR1 mRNA in relation to obesity, clinical and metabolic variables, adipocyte function, and adiponectin (ADIPOQ) levels. Methods: We assessed sc fat biopsies from 96 obese and nonobese subjects and omental fat biopsies from 82 obese and nonobese subjects. Results: The sc and omental adipose CNR1 gene expression were similar in obese and nonobese subjects. No association between either sc or omental adipose CNR1 mRNA levels and body mass index, waist circumference, plasma levels of glucose and insulin, lipids, or blood pressure was found. The sc and omental maximal adrenergic lipolytic activation as well as lipolytic adrenoceptor sensitivity were not related to CNR1 gene expression. Lipogenesis in sc adipocytes also showed no association with CNR1 mRNA levels. Finally, no relation was found between adipose CNR1 gene expression and ADIPOQ mRNA, adipose tissue adiponectin secretion, or circulating adiponectin. Conclusion: We found no association of human adipose tissue CNR1 mRNA expression with measures of body fat, metabolic parameters, fat cell function, or ADIPOQ expression. These data do not suggest a major role of human adipose CNR1 in fat cell function or metabolic disease development.

Diurnal rhythms and effects of fasting and refeeding on rat adipose tissue lipoprotein lipase

1996 ◽  
Vol 271 (6) ◽  
pp. E1092-E1097 ◽  
Author(s):  
M. Bergo ◽  
G. Olivecrona ◽  
T. Olivecrona
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Specific Activity ◽  
Early Morning ◽  
Diurnal Rhythms ◽  
Mrna Levels ◽  
Short Term ◽  
Early Afternoon ◽  
Rat Adipose Tissue ◽  
Adipose Tissue Lipoprotein Lipase

The activity of lipoprotein lipase (LPL) in adipose tissue is modulated by changes in the nutritional status. We have measured LPL activity, mass, and mRNA levels in rat adipose tissue during normal feeding cycles, during short- and long-term fasting, and during refeeding after fasting. LPL activity displayed a diurnal rhythm. The activity was highest during the night and early morning, decreased to a minimum during the early afternoon, and then increased again. These changes corresponded to the feeding pattern. The increases and/or decreases resulted from changes in LPL synthetic rate compounded by posttranslational mechanisms. During short-term fasting, LPL specific activity decreased to < 30% of control. The specific activity was restored within 4 h by refeeding. On longer fasting, LPL mRNA decreased. This became significant from 36 h. On refeeding, it took 12 h to restore the mRNA levels, whereas tissue LPL activity and mass could not be fully restored by 36 h of refeeding. These data show that LPL activity during short-term fasting is regulated posttranscriptionally, which allows for quick upregulation after refeeding. On longer fasting, other mechanisms affecting LPL transcription and synthesis come into play, and upregulation after refeeding is slowed down.

Influence of age, fat cell weight, and obesity on O2 consumption of human adipose tissue

1989 ◽  
Vol 256 (4) ◽  
pp. E467-E474 ◽  
Author(s):  
P. Hallgren ◽  
L. Sjostrom ◽  
H. Hedlund ◽  
L. Lundell ◽  
L. Olbe
Keyword(s):  
Adipose Tissue ◽  
Oxygen Consumption ◽  
Energy Expenditure ◽  
Human Adipose Tissue ◽  
Fat Cell ◽  
Cell Weight ◽  
Total Body ◽  
Obese Human ◽  
Open Question ◽  
Partial Weight

The oxygen consumption of human adipose tissue (AT) was determined in 53 adults, lean and obese, and in nine lean boys. The oxygen consumption was positively related to fat cell weight and negatively to age and degree of obesity. Men and women did not differ with respect to oxygen consumption of AT. The positive relationship between oxygen consumption per cell and fat cell size was also demonstrated in size-separated cells from the same donors. Expressed per cell the oxygen consumption was higher in fat cells from obese than in cells from lean subjects, but expressed per gram of tissue the opposite result was found. The oxygen consumption of the total AT organ was higher in obese than in lean subjects. The energy expenditure of AT constituted approximately 4% of the estimated 24-h energy expenditure in both groups. It is concluded that obese subjects do not maintain their obesity because of a reduced energy expenditure of the total AT (or of the total body). After a partial weight reduction in five subjects, the energy metabolism tended to change in direction toward the conditions seen in lean subjects. However, it is still an open question whether the observed energy metabolic aberrations of obese human AT are only secondary to the obese state or partly primary and thus of etiological importance.

scholarly journals Genetic ablation of adipocyte PD-L1 reduces tumor growth but accentuates obesity-associated inflammation

2020 ◽  
Vol 8 (2) ◽  
pp. e000964 ◽  
Author(s):  
Bogang Wu ◽  
Huai-Chin Chiang ◽  
Xiujie Sun ◽  
Bin Yuan ◽  
Payal Mitra ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Tumor Growth ◽  
Body Weight Gain ◽  
High Body Mass Index ◽  
Human Adipose Tissue ◽  
Mrna Levels ◽  
Metabolic Dysfunction ◽  
Genetic Ablation ◽  
Tumor Immunosuppression

The programmed death-ligand 1 (PD-L1)-dependent immune checkpoint attenuates host immunity and maintains self-tolerance. Imbalance between protective immunity and immunopathology due to altered PD-L1 signaling can lead to autoimmunity or tumor immunosuppression. The role of the PD-L1-dependent checkpoint in non-immune system is less reported. We previously found that white adipocytes highly express PD-L1. Here we show that adipocyte-specific PD-L1 knockout mice exhibit enhanced host anti-tumor immunity against mammary tumors and melanoma with low or no tumor PD-L1. However, adipocyte PD-L1 ablation in tumor-free mice also exacerbates diet-induced body weight gain, pro-inflammatory macrophage infiltration into adipose tissue, and insulin resistance. Low PD-L1 mRNA levels in human adipose tissue correlate with high body mass index and presence of type 2 diabetes. Therefore, our mouse genetic approach unequivocally demonstrates a cell-autonomous function of adipocyte PD-L1 in promoting tumor growth and inhibiting antitumor immunity. In addition, our work uncovers a previously unrecognized role of adipocyte PD-L1 in mitigating obesity-related inflammation and metabolic dysfunction.

Targeted inhibition of CD74 attenuates adipose COX-2-MIF-mediated M1 macrophage polarization and retards obesity-related adipose tissue inflammation and insulin resistance

2018 ◽  
Vol 132 (14) ◽  
pp. 1581-1596 ◽  
Author(s):  
Pei-Chi Chan ◽  
Ting-Ni Wu ◽  
Ying-Chuan Chen ◽  
Chieh-Hua Lu ◽  
Martin Wabitsch ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Inflammatory Responses ◽  
Macrophage Polarization ◽  
Mrna Levels ◽  
Model Assessment ◽  
M1 Macrophage ◽  
Cox 2 ◽  
Highly Correlated ◽  
Targeted Inhibition

Adipose tissue (AT) inflammation is crucial to the development of obesity-associated insulin resistance. Our aim was to investigate the contribution of cyclooxygenase-2 (COX-2)/macrophage migration inhibitory factor (MIF)-mediated cross-talk between hypertrophic adipocytes and macrophages to the etiology of AT inflammation and the involvement of CD74 using human SGBS adipocytes, THP-1 macrophages and mice fed a high-fat (HF) diet. The MIF and CD74 mRNA levels in the adipocytes and stromal vascular cells (SVCs) of white fat were highly correlated with body weight (BW), homeostatic model assessment for insulin resistance (HOMA-IR), and adipose macrophage marker expression levels, especially those in SVCs. COX-2 inhibition suppressed the elevation of MIF production in HF white adipocytes as well as palmitate and hypoxic-treated SGBS adipocytes. Treatment of adipocytes transfected with shCOX-2 and siMIF or subjected to MIF depletion in the medium reversed the pro-inflammatory responses in co-incubated THP-1 cells. Inhibition of NF-κB activation reversed the COX2-dependent MIF secretion from treated adipocytes. The targeted inhibition of macrophage CD74 prevented M1 macrophage polarization in the above co-culture model. The COX-2-dependent increases in CD74 gene expression and MIF release in M1-polarized macrophages facilitated the expression of COX-2 and MIF in co-cultured SGBS adipocytes. CD74 shRNA intravenous injection suppressed HF-induced AT M1 macrophage polarization and inflammation as well as insulin resistance in mice. The present study suggested that COX-2-mediated MIF secretion through NF-κB activation from hypertrophic and hypoxic adipocytes as well as M1 macrophages might substantially contribute to the phenotypic switch of AT macrophages through CD74 in obesity. Inhibition of CD74 could attenuate AT inflammation and insulin resistance in the development of HF diet-induced obesity.

scholarly journals A long-non-coding RNA, LINC00473, confers the human adipose tissue thermogenic phenotype through enhanced cAMP responsiveness

2018 ◽  
Author(s):  
Khanh-Van Tran ◽  
Cecilie Nandrup-Bus ◽  
Tiffany DeSouza ◽  
Ricardo Soares ◽  
Naja Zenius Jespersen ◽  
...  
Keyword(s):  
Metabolic Disease ◽  
Adipose Tissue ◽  
Disease Risk ◽  
Human Adipose Tissue ◽  
Non Coding Rna ◽  
Highly Correlated ◽  
Thermogenic Adipocytes ◽  
The Many ◽  
External Stimuli ◽  
Long Non Coding Rna

SummarySpecialized adipocytes localized in distinct depots mediate the many physiological functions of adipose tissue. In humans, paucity of thermogenic adipocytes correlates with high metabolic disease risk, raising much interest in the mechanisms by which these cells arise. Here we report molecular signatures associated with adipocyte development in different human depots and identify a long non-coding RNA, LINC00473, as the transcript most closely associated with enrichment of thermogenic adipocytes. LINC00473 expression is low in subjects with obesity or type-2 diabetes and is highly correlated with cAMP signaling and mitochondrial oxidative phosphorylation pathways. LINC00473 is localized in the nucleus and the cytoplasm, and its knockdown impairs induction of UCP1 and mitochondrial respiration. These results reveal that depot-enriched genes that modulate responsiveness to external stimuli, specifically LINC00473, are important determinants of the adipose tissue thermogenic phenotype, and potential targets for metabolic disease therapy.

scholarly journals PCDD/FS LEVEL IN HUMAN ADIPOSE TISSUE OF BIENHOA RESIDENTS IN COMPARISON WITH DEVELOPED INDUSTRIAL COUNTRIES

2011 ◽  
Vol 14 (1) ◽  
pp. 92-106
Author(s):  
Anh Tuan Mai
Keyword(s):  
Nervous System ◽  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Developed Countries ◽  
Industrial Countries ◽  
Southern Vietnam ◽  
Dioxin Concentration ◽  
Wide Range ◽  
The Developed Countries ◽  
People Group

Dioxin exhibits serious health effects when it reaches as concentration a few ppt in human body fat. Dioxin is a powerful hormone disrupting chemical. By binding to a cell's hormone receptor, it literally modifies the functioning and genetic mechanism of the cell, causing a wide range of effects, from cancer to reduced immunity, nervous system disorders, miscarriages and birth deformity. Median i-TEQ in adipose tissue of the BienHoa residents is comparable with that of the developed countries while mean i-TEQ of the Bien Hoa residents is higher in both groups, especially older people group. This group has some exceptional cases with i-TEQ value up to 1148.7pg/g. The i-TEQ value in our studies is higher than that conducted by other studies. However, our result supports a conclusion: at present, the dioxin concentration in natural environment and human bodies in Southern Vietnam is only a residue and not higher than that in developed countries.

scholarly journals Effect of Age and Lipoperoxidation in Rat and Human Adipose Tissue-Derived Stem Cells

2020 ◽  
Vol 2020 ◽  
pp. 1-20
Author(s):  
Mario F. Muñoz ◽  
Sandro Argüelles ◽  
Francesco Marotta ◽  
Mario Barbagallo ◽  
Mercedes Cano ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Stem Cells ◽  
Adipose Tissue ◽  
Stem Cell ◽  
Cell Biology ◽  
Adult Stem Cells ◽  
Elongation Factor ◽  
Human Adipose Tissue ◽  
Wide Range ◽  
Proliferation And Differentiation

A wide range of clinical applications in regenerative medicine were opened decades ago with the discovery of adult stem cells. Highly promising adult stem cells are mesenchymal stem/stromal cells derived from adipose tissue (ADSCs), primarily because of their abundance and accessibility. These cells have multipotent properties and have been used extensively to carry out autologous transplants. However, the biology of these cells is not entirely understood. Among other factors, the regeneration capacity of these cells will depend on both their capacity of proliferation/differentiation and the robustness of the biochemical pathways that allow them to survive under adverse conditions like those found in damaged tissues. The transcription factors, such as Nanog and Sox2, have been described as playing an important role in stem cell proliferation and differentiation. Also, the so-called longevity pathways, in which AMPK and SIRT1 proteins play a crucial role, are essential for cell homeostasis under stressful situations. These pathways act by inhibiting the translation through downregulation of elongation factor-2 (eEF2). In order to deepen knowledge of mesenchymal stem cell biology and which factors are determinant in the final therapeutic output, we evaluate in the present study the levels of all of these proteins in the ADSCs from humans and rats and how these levels are affected by aging and the oxidative environment. Due to the effect of aging and oxidative stress, our results suggest that before performing a cell therapy with ADSCs, several aspects reported in this study such as oxidative stress status and proliferation and differentiation capacity should be assessed on these cells. This would allow us to know the robustness of the transplanted cells and to predict the therapeutic result, especially in elder patients, where probably ADSCs do not carry out their biological functions in an optimal way.

Lipogenesis and lipoprotein lipase in human adipose tissue: reproducibility of measurements and relationships with fat cell size

1984 ◽  
Vol 62 (12) ◽  
pp. 1448-1452 ◽  
Author(s):  
Roland Savard ◽  
Yves Deshaies ◽  
Jean-Pierre Després ◽  
Martine Marcotte ◽  
Ludwik Bukowiecki ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Lipase Activity ◽  
Tissue Sample ◽  
High Reliability ◽  
Human Adipose Tissue ◽  
Cell Diameter ◽  
Lipoprotein Lipase Activity ◽  
Fat Cell ◽  
Cell Weight

Lipogenesis from glucose and lipoprotein lipase activity were investigated in humans. The reliability of measurements was quantified and correlations with fat cell weight were assessed. Twenty-four subjects (7 women, 17 men) were studied twice within a 2-week period, along with 17 additional male subjects who were studied once and used only in the correlation analyses. All subjects were not regularly involved in an exercise-training program and were between 18 and 30 years of age. Following an overnight fast, adipose tissue specimens were obtained by suprailiac biopsy and fat cells were collagenase isolated. Mean fat cell weight was obtained from 400 to 500 cell diameter determinations per subject. Basal and insulin-stimulated fat cell lipogenesis from glucose were determined using D-[U-14C]glucose and were reported in nanomoles of glucose per hour per 106 cells. Adipose tissue heparin-releasable lipoprotein lipase activity was also determined and expressed in micromoles of free fatty acids per hour per gram of tissue and per 106 cells. Fat cell weight, basal and insulin-stimulated lipogenesis and lipoprotein lipase activity per gram showed high reliability of measurement, interclass and intraclass coefficients being 0.83 and over. Lipoprotein lipase activity per 106 cells showed a somewhat lower degree of reliability, interclass and intraclass coefficients being, respectively, 0.69 and 0.81. On the other hand, fat cell weight was positively correlated with lipoprotein lipase activity (r = 0.80), while no significant correlation was observed between basal lipogenesis and fat cell weight. Moreover, basal lipogenesis presented no significant correlation with lipoprotein lipase activity. These results suggest that, under standardized conditions, and from a single tissue sample, human adipose tissue lipoprotein lipase activity and fat cell lipogenesis can be measured with a satisfactory level of reliability. They also suggest that lipoprotein lipase activity is highly related with adipocyte lipid content.

scholarly journals Diversity of lipid mediators in human adipose tissue depots

2013 ◽  
Vol 304 (12) ◽  
pp. C1141-C1149 ◽  
Author(s):  
Joan Clària ◽  
Binh T. Nguyen ◽  
Arin L. Madenci ◽  
C. Keith Ozaki ◽  
Charles N. Serhan
Keyword(s):  
Adipose Tissue ◽  
Cell Metabolism ◽  
Human Adipose Tissue ◽  
Lipid Mediators ◽  
Anatomical Location ◽  
Fat Cell ◽  
Perivascular Adipose Tissue ◽  
Fat Depots ◽  
Fat Depot ◽  
Marked Deficit

Adipose tissue is a heterogeneous organ with remarkable variations in fat cell metabolism depending on the anatomical location. However, the pattern and distribution of bioactive lipid mediators between different fat depots and their relationships in complex diseases have not been investigated. Using LC-MS/MS-based metabolo-lipidomics, here we report that human subcutaneous (SC) adipose tissues possess a range of specialized proresolving mediators (SPM) including resolvin (Rv) D1, RvD2, protectin (PD) 1, lipoxin (LX) A4, and the monohydroxy biosynthetic pathway markers of RvD1 and PD1 (17-HDHA), RvE1 (18-HEPE), and maresin 1 (14-HDHA). The “classic” eicosanoids prostaglandin (PG) E2, PGD2, PGF2α, leukotriene (LT) B4, 5-hydroxyeicosatetraenoic acid (5-HETE), 12-HETE, and 15-HETE were also identified in SC fat. SC fat from patients with peripheral vascular disease (PVD) exhibited a marked deficit in PD1 and 17-HDHA levels. Compared with SC, perivascular adipose tissue displayed higher SPM levels, suggesting an enhanced resolution capacity in this fat depot. In addition, augmented levels of eicosanoids and SPM were observed in SC fat surrounding foot wounds. Notably, the profile of SC PGF2αdiffered significantly when patients were grouped by body mass index (BMI). In the case of peri-wound SC fat, BMI negatively correlated with PGE2.In this tissue, proresolving mediators RvD2 and LXA4were identified in lower levels than the proinflammatory LTB4. Collectively, these findings demonstrate a diverse distribution of bioactive lipid mediators depending on the localization of human fat depots and uncover a specific SPM pattern closely associated with PVD.

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