THU0076 Antibodies to citrullinated protein antigens (ACPAS) induce adipose tissue dysfunction impairing adipocyte differentiation, lipid accumulation and promoting macrophage polarisation. in vitro effect of biologic dmards

Endotrophin is a cleavage product of collagen 6 (Col6) in adipose tissue (AT). Previously, we demonstrated that endotrophin serves as a costimulator to trigger fibrosis and inflammation within the unhealthy AT milieu. However, how endotrophin affects lipid storage and breakdown in AT and how different cell types in AT respond to endotrophin stimulation remain unknown. In the current study, by using a doxycycline-inducible mouse model, we observed significant upregulation of adipogenic genes in the white AT (WAT) of endotrophin transgenic mice. We further showed that the mice exhibited inhibited lipolysis and accelerated hypertrophy and hyperplasia in WAT. To investigate the effects of endotrophin in vitro, we incubated different cell types from AT with conditioned medium from endotrophin-overexpressing 293T cells. We found that endotrophin activated multiple pathological pathways in different cell types. Particularly in 3T3-L1 adipocytes, endotrophin triggered a fibrotic program by upregulating collagen genes and promoted abnormal lipid accumulation by downregulating hormone-sensitive lipolysis gene and decreasing HSL phosphorylation levels. In macrophages isolated from WAT, endotrophin stimulated higher expression of the collagen-linking enzyme lysyl oxidase and M1 proinflammatory marker genes. In the stromal vascular fraction isolated from WAT, endotrophin induced upregulation of both profibrotic and proinflammatory genes. In conclusion, our study provides a new perspective on the effect of endotrophin in abnormal lipid accumulation and a mechanistic insight into the roles played by adipocytes and a variety of other cell types in AT in shaping the unhealthy microenvironment upon endotrophin treatment.

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Interactive in vitro effect of prolactin, growth hormone and season on leptin secretion by ovine adipose tissue

Small Ruminant Research ◽

10.1016/j.smallrumres.2011.06.010 ◽

2011 ◽

Vol 100 (2-3) ◽

pp. 177-183 ◽

Cited By ~ 3

Author(s):

M. Szczesna ◽

D.A. Zieba ◽

B. Klocek-Gorka ◽

D.H. Keisler

Keyword(s):

Growth Hormone ◽

Adipose Tissue ◽

Vitro Effect

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JAZF1 heterozygous knockout mice show altered adipose development and metabolism

Cell & Bioscience ◽

10.1186/s13578-021-00625-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Jain Jeong ◽

Soyoung Jang ◽

Song Park ◽

Wookbong Kwon ◽

Si-Yong Kim ◽

...

Keyword(s):

Adipose Tissue ◽

Knockout Mice ◽

Metabolic Disorders ◽

Adipocyte Differentiation ◽

Zinc Finger Protein ◽

Tissue Mass ◽

In Vivo Models ◽

Brown Adipose

Abstract Background Juxtaposed with another zinc finger protein 1 (JAZF1) is associated with metabolic disorders, including type 2 diabetes mellitus (T2DM). Several studies showed that JAZF1 and body fat mass are closely related. We attempted to elucidate the JAZF1 functions on adipose development and related metabolism using in vitro and in vivo models. Results The JAZF1 expression was precisely regulated during adipocyte differentiation of 3T3-L1 preadipocyte and mouse embryonic fibroblasts (MEFs). Homozygous JAZF1 deletion (JAZF1-KO) resulted in impaired adipocyte differentiation in MEF. The JAZF1 role in adipocyte differentiation was demonstrated by the regulation of PPARγ—a key regulator of adipocyte differentiation. Heterozygous JAZF1 deletion (JAZF1-Het) mice fed a normal diet (ND) or a high-fat diet (HFD) had less adipose tissue mass and impaired glucose homeostasis than the control (JAZF1-Cont) mice. However, other metabolic organs, such as brown adipose tissue and liver, were negligible effect on JAZF1 deficiency. Conclusion Our findings emphasized the JAZF1 role in adipocyte differentiation and related metabolism through the heterozygous knockout mice. This study provides new insights into the JAZF1 function in adipose development and metabolism, informing strategies for treating obesity and related metabolic disorders.

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Generation of immune cell containing adipose organoids for in vitro analysis of immune metabolism

Scientific Reports ◽

10.1038/s41598-020-78015-9 ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Jacqueline Taylor ◽

Julia Sellin ◽

Lars Kuerschner ◽

Lennart Krähl ◽

Yasmin Majlesain ◽

...

Keyword(s):

Adipose Tissue ◽

Adipocyte Differentiation ◽

Immune Cell ◽

Stromal Vascular Fraction ◽

Cell Populations ◽

Endocrine Organ ◽

Vitro Analysis ◽

In Vitro Analysis ◽

Better Than

AbstractAdipose tissue is an organized endocrine organ with important metabolic and immunological functions and immune cell-adipocyte crosstalk is known to drive various disease pathologies. Suitable 3D adipose tissue organoid models often lack resident immune cell populations and therefore require the addition of immune cells isolated from other organs. We have created the first 3D adipose tissue organoid model which could contain and maintain resident immune cell populations of the stromal vascular fraction (SVF) and proved to be effective in studying adipose tissue biology in a convenient manner. Macrophage and mast cell populations were successfully confirmed within our organoid model and were maintained in culture without the addition of growth factors. We demonstrated the suitability of our model for monitoring the lipidome during adipocyte differentiation in vitro and confirmed that this model reflects the physiological lipidome better than standard 2D cultures. In addition, we applied mass spectrometry-based lipidomics to track lipidomic changes in the lipidome upon dietary and immunomodulatory interventions. We conclude that this model represents a valuable tool for immune-metabolic research.

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Angiogenic Deficiency and Adipose Tissue Dysfunction Are Associated with Macrophage Malfunction in SIRT1−/− Mice

Endocrinology ◽

10.1210/en.2011-1667 ◽

2012 ◽

Vol 153 (4) ◽

pp. 1706-1716 ◽

Cited By ~ 40

Author(s):

Fen Xu ◽

David Burk ◽

Zhanguo Gao ◽

Jun Yin ◽

Xia Zhang ◽

...

Keyword(s):

Adipose Tissue ◽

Adipocyte Differentiation ◽

Nuclear Factor Κb ◽

The Body ◽

Sirtuin 1 ◽

Vascular Density ◽

Peroxisome Proliferator ◽

Wild Type ◽

Peroxisome Proliferator Activated Receptor

The histone deacetylase sirtuin 1 (SIRT1) inhibits adipocyte differentiation and suppresses inflammation by targeting the transcription factors peroxisome proliferator-activated receptor γ and nuclear factor κB. Although this suggests that adiposity and inflammation should be enhanced when SIRT1 activity is inactivated in the body, this hypothesis has not been tested in SIRT1 null (SIRT1−/−) mice. In this study, we addressed this issue by investigating the adipose tissue in SIRT1−/− mice. Compared with their wild-type littermates, SIRT1 null mice exhibited a significant reduction in body weight. In adipose tissue, the average size of adipocytes was smaller, the content of extracellular matrix was lower, adiponectin and leptin were expressed at 60% of normal level, and adipocyte differentiation was reduced. All of these changes were observed with a 50% reduction in capillary density that was determined using a three-dimensional imaging technique. Except for vascular endothelial growth factor, the expression of several angiogenic factors (Pdgf, Hgf, endothelin, apelin, and Tgf-β) was reduced by about 50%. Macrophage infiltration and inflammatory cytokine expression were 70% less in the adipose tissue of null mice and macrophage differentiation was significantly inhibited in SIRT1−/− mouse embryonic fibroblasts in vitro. In wild-type mice, macrophage deletion led to a reduction in vascular density. These data suggest that SIRT1 controls adipose tissue function through regulation of angiogenesis, whose deficiency is associated with macrophage malfunction in SIRT1−/− mice. The study supports the concept that inflammation regulates angiogenesis in the adipose tissue.

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Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation

Journal of Endocrinology ◽

10.1530/joe-14-0425 ◽

2014 ◽

Vol 223 (2) ◽

pp. 119-132 ◽

Cited By ~ 9

Author(s):

M van de Vyver ◽

E Andrag ◽

I L Cockburn ◽

W F Ferris

Keyword(s):

Adipose Tissue ◽

Lipid Droplet ◽

Lipid Accumulation ◽

Adipogenic Differentiation ◽

Chronic Administration ◽

Droplet Formation ◽

Pcr Analysis ◽

Mineral Density ◽

Lipid Droplet Formation

Chronic administration of the insulin-sensitising drugs, thiazolidinediones (TZDs), results in low bone mineral density and ‘fatty bones’. This is thought to be due, at least in part, to aberrant differentiation of progenitor mesenchymal stem cells (MSCs) away from osteogenesis towards adipogenesis. This study directly compared the effects of rosiglitazone, pioglitazone, and netoglitazone treatment on osteogenesis and adipogenesis in MSCs derived from subcutaneous (SC) or visceral (PV) white adipose tissue. MSCs were isolated from adipose tissue depots of male Wistar rats and characterised using flow cytometry. The effects of TZD treatment on osteogenic and adipogenic differentiation were assessed histologically (day 14) and by quantitative PCR analysis (Pparγ2(Pparg2),Ap2(Fabp4), Adipsin(Adps),Msx2, Collagen I(Col1a1), andAlp) on days 0, 7, and 10. Uniquely, lipid droplet formation and mineralisation were found to occur concurrently in response to TZD treatment during osteogenesis. Compared with SC MSCs, PV MSCs were more prone to lipid accumulation under controlled osteogenic and adipogenic differentiation conditions. This study demonstrated that the extent of lipid accumulation is dependent on the nature of thePparligand and that SC and PV MSCs respond differently toin vitroTZD treatment, suggesting that metabolic status can contribute to the adverse effects associated with TZD treatment.

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Antiobesity activity of Acer tegmentosum Maxim on 3T3-L1 preadipocyte and high-fat diet-induced obese rats

10.21203/rs.2.24283/v1 ◽

2020 ◽

Author(s):

Hang-Hee Cho ◽

Soo-Jung Lee ◽

Sung-Ho Kim ◽

Sun-Hee Jang ◽

Chungkil Won ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Acid ◽

Lipid Accumulation ◽

High Fat Diet ◽

Adipocyte Differentiation ◽

Binding Protein ◽

High Fat ◽

Tissue Mass ◽

Fatty Acid Binding ◽

Obese Rats

Abstract Background: The aim of this study was to investigate the effect of Acer tegmentosum Maxim (ATM) on adipocyte differentiation in 3T3-L1 adipocyte-derived cells and anti-obesity properties in high fat diet (HFD)-induced obese rats. Methods: 3T3-L1 adipocytes and HFD-induced obese rats were treated with ATM, and its effect on gene expression was analyzed using RT-PCR and Western blotting experiments. Results: Cellular lipid contents in DMI (dexamethasone, 3-isobutyl-1-methylxanthine, and insulin mixture)-treated cells increased, while ATM treatment caused a significant reduction in lipid accumulation in differentiated 3T3-L1 cells. ATM caused inhibition of adipogenesis via down-regulation of the CCAAT/enhancer binding protein β (C/EBPβ), C/EBPα, and peroxisome proliferator-activated receptor γ (PPARγ) expressions in 3T3-L1 cells. Moreover, treatment with ATM caused a decrease in the expressions of adipocyte-specific genes, such as adipocyte fatty acid-binding protein-2 (aP2), fatty acid synthase (FAS), and lipoprotein lipase (LPL), compared with DMI-stimulated adipocytes. In addition, phosphorylation levels of protein kinase B (Akt) and its downstream substrate, glycogen synthase kinase 3β (GSK3β), were significantly decreased by ATM treatment of 3T3-L1 adipocytes. Together, these results indicated that ATM caused inhibition of both adipocyte differentiation via suppression of the C/EBP family and PPARγ expressions and the Akt signaling pathway in 3T3-L1 adipocytes. In the present study, we further investigated anti-obesity effects of ATM on HFD-induced obese rats. Rats fed with HFD demonstrated elevations in body weight gain, while the administration of ATM significantly reversed BW gains and adipose tissue weights in rats fed HFD. ATM supplementation also caused a decrease in the circulating triglyceride levels and total cholesterol levels and led to inhibition of lipid accumulation in the adipose tissues in HFD-induced obesity in rats. Furthermore, epididymal fat exhibited larger adipocytes in the HFD group, whereas the ATM-treated group was significantly smaller than that of HFD group. These results strongly demonstrate that ATM administration caused a reduction in adiposity via attenuation in adipose tissue mass and adipocyte size. Conclusion: These finding demonstrated that ATM exerted anti-obesity effects through inhibition of adipocyte differentiation and adipogenesis, leading to a decrease in BW and fat tissue mass in HFD-induced obesity in rats.

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Molecular and Cellular Bases of Lipodystrophy Syndromes

Frontiers in Endocrinology ◽

10.3389/fendo.2021.803189 ◽

2022 ◽

Vol 12 ◽

Author(s):

Jamila Zammouri ◽

Camille Vatier ◽

Emilie Capel ◽

Martine Auclair ◽

Caroline Storey-London ◽

...

Keyword(s):

Adipose Tissue ◽

Fatty Liver Disease ◽

Adipocyte Differentiation ◽

Systemic Diseases ◽

Partial Loss ◽

Metabolic Complications ◽

Nonalcoholic Fatty Liver ◽

Adipose Tissue Dysfunction ◽

Gonadotropic Axis ◽

Molecular Bases

Lipodystrophy syndromes are rare diseases originating from a generalized or partial loss of adipose tissue. Adipose tissue dysfunction results from heterogeneous genetic or acquired causes, but leads to similar metabolic complications with insulin resistance, diabetes, hypertriglyceridemia, nonalcoholic fatty liver disease, dysfunctions of the gonadotropic axis and endocrine defects of adipose tissue with leptin and adiponectin deficiency. Diagnosis, based on clinical and metabolic investigations, and on genetic analyses, is of major importance to adapt medical care and genetic counseling. Molecular and cellular bases of these syndromes involve, among others, altered adipocyte differentiation, structure and/or regulation of the adipocyte lipid droplet, and/or premature cellular senescence. Lipodystrophy syndromes frequently present as systemic diseases with multi-tissue involvement. After an update on the main molecular bases and clinical forms of lipodystrophy, we will focus on topics that have recently emerged in the field. We will discuss the links between lipodystrophy and premature ageing and/or immuno-inflammatory aggressions of adipose tissue, as well as the relationships between lipomatosis and lipodystrophy. Finally, the indications of substitutive therapy with metreleptin, an analog of leptin, which is approved in Europe and USA, will be discussed.

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