scholarly journals Amidation-Modified Apelin-13 Regulates PPARγ and Perilipin to Inhibit Adipogenic Differentiation and Promote Lipolysis

2021 ◽  
Vol 2021 ◽  
pp. 1-9
Author(s):  
Sha Wang ◽  
Guoying Gao ◽  
Yiwei He ◽  
Qiong Li ◽  
Zhan Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Adipogenic Differentiation ◽  
Animal Experiments ◽  
Endocrine System ◽  
Average Diameter ◽  
Lifestyle Changes ◽  
Biologically Active ◽  
Regulation Mechanism ◽  
Prevalence Of Obesity

With the adjustment of human diet and lifestyle changes, the prevalence of obesity is increasing year by year. Obesity is closely related to the excessive accumulation of white adipose tissue (WAT), which can synthesize and secrete a variety of adipokines. Apelin is a biologically active peptide in the adipokines family. Past studies have shown that apelin plays an important regulatory role in the pathogenesis and pathophysiology of diseases such as the cardiovascular system, respiratory system, digestive system, nervous system, and endocrine system. Apelin is also closely related to diabetes and obesity. Therefore, we anticipate that apelin-13 has an effect on lipometabolism and intend to explore the effect of apelin-13 on lipometabolism at the cellular and animal levels. In in vitro experiments, amidation-modified apelin-13 can significantly reduce the lipid content; TG content; and the expression of PPARγ, perilipin mRNA, and protein in adipocytes. Animal experiments also show that amidation modification apelin-13 can improve the abnormal biochemical indicators of diet-induced obesity (DOI) rats and can reduce the average diameter of adipocytes in adipose tissue, the concentration of glycerol, and the expression of PPARγ and perilipin mRNA and protein. Our results show that apelin-13 can affect the metabolism of adipose tissue, inhibit adipogenic differentiation of adipocytes, promote lipolysis, and thereby improve obesity. The mechanism may be regulating the expression of PPARγ to inhibit adipogenic differentiation and regulating the expression of perilipin to promote lipolysis. This study helps us understand the role of apelin-13 in adipose tissue and provide a basis for the elucidation of the regulation mechanism of lipometabolism and the development of antiobesity drugs.

Neonatal IL-4 exposure decreases adipogenesis of male rats into adulthood

2021 ◽  
Author(s):  
Tammy Ying ◽  
Thea N. Golden ◽  
Lan Cheng ◽  
Jeff Ishibashi ◽  
Patrick Seale ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Neonatal Period ◽  
Uncoupling Protein ◽  
Adipogenic Differentiation ◽  
Male Rats ◽  
Interleukin 4 ◽  
Sprague Dawley ◽  
Fat Cell ◽  
Subcutaneous White Adipose Tissue

The cytokine interleukin 4 (IL-4) can increase beige adipogenesis in adult rodents. However, neonatal animals use a distinct adipocyte precursor compartment for adipogenesis compared to adults. In this study, we address whether IL-4 can induce persistent effects on adipose tissue when administered subcutaneously in the interscapular region during the neonatal period in Sprague Dawley rats. We injected IL-4 into neonatal male rats during postnatal days 1-6, followed by analysis of adipose tissue and adipocyte precursors at 2 weeks and 10 weeks of age. Adipocyte precursors were cultured and subjected to differentiation in vitro. We found that a short and transient IL-4 exposure in neonates upregulated uncoupling protein 1 (Ucp1) mRNA expression and decreased fat cell size in subcutaneous white adipose tissue (WAT). Adipocyte precursors from mature rats that had been treated with IL-4 as neonates displayed a decrease in adiponectin (Adipoq) but no change in Ucp1 expression, as compared to controls. Thus, neonatal IL-4 induces acute beige adipogenesis and decreases adipogenic differentiation capacity long term. Overall, these findings indicate that the neonatal period is critical for adipocyte development and may influence the later onset of obesity.

scholarly journals Inflammatory Microenvironment and Adipogenic Differentiation in Obesity: The Inhibitory Effect of Theobromine in a Model of Human Obesity In Vitro

2019 ◽  
Vol 2019 ◽  
pp. 1-10 ◽  
Author(s):  
Maria Pia Fuggetta ◽  
Manuela Zonfrillo ◽  
Cristina Villivà ◽  
Enzo Bonmassar ◽  
Giampiero Ravagnan
Keyword(s):  
Adipose Tissue ◽  
Proinflammatory Cytokines ◽  
Adipogenic Differentiation ◽  
Inhibitory Effect ◽  
Low Grade ◽  
Tissue Inflammation ◽  
Inflammatory Microenvironment ◽  
Adipocyte Cell ◽  
Inflammatory State

Objective. Obesity is considered a clinic condition characterized by a state of chronic low-grade inflammation. The role of macrophages and adipocytokines in adipose tissue inflammation is in growing investigation. The physiopathological mechanisms involved in inflammatory state in obesity are not fully understood though the adipocytokines seem to characterize the biochemical link between obesity and inflammation. The aim of this work is to analyze the effect of theobromine, a methylxanthine present in the cocoa, on adipogenesis and on proinflammatory cytokines evaluated in a model of fat tissue inflammation in vitro. Methods. In order to mimic in vitro this inflammatory condition, we investigated the interactions between human-like macrophages U937 and human adipocyte cell lines SGBS. The effect of theobromine on in vitro cell growth, cell cycle, adipogenesis, and cytokines release in the supernatants has been evaluated. Results. Theobromine significantly inhibits the differentiation of preadipocytes in mature adipocytes and reduces the levels of proinflammatory cytokines as MCP-1 and IL-1β in the supernatants obtained by the mature adipocytes and macrophages interaction. Conclusion. Theobromine reduces adipogenesis and proinflammatory cytokines; these data suggest its potential therapeutic effect for treating obesity by control of macrophages infiltration in adipose tissue and inflammation.

scholarly journals “The preadipocyte factor” DLK1 marks adult mouse adipose tissue residing vascular cells that lack in vitro adipogenic differentiation potential

FEBS Letters ◽  
2009 ◽  
Vol 583 (17) ◽  
pp. 2947-2953 ◽  
Author(s):  
Ditte Caroline Andersen ◽  
Line Jensen ◽  
Henrik Daa Schrøder ◽  
Charlotte Harken Jensen
Keyword(s):  
Adipose Tissue ◽  
Adult Mouse ◽  
Adipogenic Differentiation ◽  
Vascular Cells ◽  
Differentiation Potential

scholarly journals Thiazolidinedione-induced lipid droplet formation during osteogenic differentiation

2014 ◽  
Vol 223 (2) ◽  
pp. 119-132 ◽  
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.

scholarly journals Adipocyte Biology from the Perspective of In Vivo Research: Review of Key Transcription Factors

2021 ◽  
Vol 23 (1) ◽  
pp. 322
Author(s):  
Maria N. Evseeva ◽  
Maria S. Balashova ◽  
Konstantin Y. Kulebyakin ◽  
Yury P. Rubtsov
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Metabolic Disorders ◽  
Adipogenic Differentiation ◽  
In Vivo Studies ◽  
Research Review ◽  
Treatment And Prevention

Obesity and type 2 diabetes are both significant contributors to the contemporary pandemic of non-communicable diseases. Both disorders are interconnected and associated with the disruption of normal homeostasis in adipose tissue. Consequently, exploring adipose tissue differentiation and homeostasis is important for the treatment and prevention of metabolic disorders. The aim of this work is to review the consecutive steps in the postnatal development of adipocytes, with a special emphasis on in vivo studies. We gave particular attention to well-known transcription factors that had been thoroughly described in vitro, and showed that the in vivo research of adipogenic differentiation can lead to surprising findings.

scholarly journals Rosiglitazone Enhances Browning Adipocytes in Association with MAPK and PI3-K Pathways During the Differentiation of Telomerase-Transformed Mesenchymal Stromal Cells into Adipocytes

2019 ◽  
Vol 20 (7) ◽  
pp. 1618 ◽  
Author(s):  
Abeer Fayyad ◽  
Amir Khan ◽  
Sallam Abdallah ◽  
Sara Alomran ◽  
Khalid Bajou ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mesenchymal Stromal Cells ◽  
Stromal Cells ◽  
Adipogenic Differentiation ◽  
Maturation Stage ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Brown Adipose ◽  
Brown Adipogenesis

Obesity is a major risk for diabetes. Brown adipose tissue (BAT) mediates production of heat while white adipose tissue (WAT) function in the storage of fat. Roles of BAT in the treatment of obesity and related disorders warrants more investigation. Peroxisome proliferator activator receptor gamma (PPAR-γ) is the master regulator of both BAT and WAT adipogenesis and has roles in glucose and fatty acid metabolism. Adipose tissue is the major expression site for PPAR-γ. In this study, the effects of rosiglitazone on the brown adipogenesis and the association of MAPK and PI3K pathways was investigated during the in vitro adipogenic differentiation of telomerase transformed mesenchymal stromal cells (iMSCs). Our data indicate that 2 µM rosiglitazone enhanced adipogenesis by over-expression of PPAR-γ and C/EBP-α. More specifically, brown adipogenesis was enhanced by the upregulation of EBF2 and UCP-1 and evidenced by multilocular fatty droplets morphology of the differentiated adipocytes. We also found that rosiglitazone significantly activated MAPK and PI3K pathways at the maturation stage of differentiation. Overall, the results indicate that rosiglitazone induced overexpression of PPAR-γ that in turn enhanced adipogenesis, particularly browning adipogenesis. This study reports the browning effects of rosiglitazone during the differentiation of iMSCs into adipocytes in association with the activation of MAPK and PI3K signaling pathways.

282 ADIPOGENIC DIFFERENTIATION IN VITRO OF PORCINE ADULT MESENCHYMAL STEM CELLS

2009 ◽  
Vol 21 (1) ◽  
pp. 238 ◽  
Author(s):  
E. Monaco ◽  
A. Lima ◽  
S. Wilson ◽  
S. Lane ◽  
M. Bionaz ◽  
...  
Keyword(s):  
Gene Expression ◽  
Stem Cells ◽  
Bone Marrow ◽  
Adipose Tissue ◽  
Subcutaneous Adipose Tissue ◽  
Adipogenic Differentiation ◽  
Expression Patterns ◽  
Mrna Abundance ◽  
Subcutaneous Adipose

The quantity and accessibility of subcutaneous adipose tissue in humans make it an attractive alternative to bone marrow as a source of adult stem cells for therapeutic purposes. However, before such a cell source substitution can be proposed, the properties of stem cells derived from adipose tissue (ADSC) and bone marrow (BMSC), and their differentiated progeny must be compared in an animal model, such as swine, that adequately simulates the structure and physiology of humans. The objective of this work was to induce adult porcine stem cells isolated from subcutaneous adipose tissue and bone marrow to differentiate in vitro along the adipogenic lineage and to compare their transcript profile properties. ADSC and BMSC were isolated from subcutaneous adipose tissue and femurs of adult pigs, respectively, and differentiated along the adipogenic lineage using specific inducing medium. Cells were incubated up to 4 weeks with medium replaced every 3 days. Histological staining with Oil Red O was performed at 0, 2, 4, 7, 14, 21, 28 days of differentiation (dd) to confirm the adipogenic differentiation. RNA was also extracted at these time points. qPCR was performed on PPARG, DBI, ACSL1, CD36, CEBPA, DGAT2, ADFP, ADIPOQ, SCD. The geometrical mean of GTF2H3, NUBP, and PPP2CB was used as an internal control. Gene expression was analyzed using a mixed model of SAS with repeated time. The adipogenic differentiation of both ADSC and BMSC was confirmed by the Oil Red O positive staining. The relative mRNA abundance of all the genes at dd0 was similar between the ADSC and BMSC. The relative mRNA abundance of most of the genes was also similar between ADSC and BMSC throughout the adipogenic differentiation. ACSL1 and ADIPOQ had analogous expression patterns among the cell types. ACSL1 had relatively large mRNA abundance before differentiation, but ADIPOQ was barely detectable. As a consequence of differentiation, ACSL1 increased in relative mRNA abundance about 10-fold, whereas ADIPOQ mRNA increased about 1000-fold. Temporal expression patterns of SCD, DGAT2, and ADFP were similar. The increase in gene expression was >800% for SCD, >500% for ADFP, and >50 000% for DGAT2 after 7dd. ADSC had significantly higher expression of those genes compared to BMSC at 14 and 28dd. Both ADIPOQ and DGAT2 were almost undetectable prior to differentiation. mRNA expression of CD36 and DBI was similar with a significantly larger increase in expression of ADSC compared with BMSC. Relative mRNA abundance of CEBPA and PPARG was also larger in ADSC compared with BMSC; however, BMSC had a remarkable increase in temporal expression of those genes throughout adipogenic differentiation. These results suggest both cell types can differentiate towards the adipogenic lineage but with quantitatively different gene expression patterns. More investigation is needed before the ADSC can be considered a practical alternative source for stem cells in future human clinical applications. This research was supported by the Illinois Regenerative Medicine Institute.

scholarly journals Biological Features Implies Potential Use of Autologous Adipose-Derived Stem/Progenitor Cells in Wound Repair and Regenerations for the Patients with Lipodystrophy

2019 ◽  
Vol 20 (21) ◽  
pp. 5505 ◽  
Author(s):  
Keiji Suzuki ◽  
Sadanori Akita ◽  
Hiroshi Yoshimoto ◽  
Akira Ohtsuru ◽  
Akiyoshi Hirano ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Progenitor Cells ◽  
Highly Active Antiretroviral Therapy ◽  
Wound Repair ◽  
Adipogenic Differentiation ◽  
Tissue Loss ◽  
Cell Based Therapy ◽  
Growth Properties ◽  
The Way

A paradigm shift in plastic and reconstructive surgery is brought about the usage of cell-based therapies for wound healing and regeneration. Considering the imitations in the reconstructive surgeries in restoring tissue loss and deficiency, stem cell-based therapy, in particular, has been expected to pave the way for a new solution to the regenerative approaches. Limitations in the reconstructive surgeries in restoring tissue loss and deficiency have paved the way for new regenerative approaches. Among them, adipose-derived stem/progenitor cells (ADSCs)-based therapy could be the most promising clue, since ADSCs have pluripotent differentiation capabilities not only in adipocytes but also in a variety of cell types. Accumulating evidences have indicated that the unfavorable development of adipose-tissue damage, namely, lipodystrophy, is a systemic complication, which is closely related to metabolic abnormality. Considering ADSC-based regenerative medicine should be applied for the treatment of lipodystrophy, it is inevitable to ascertain whether the ADSCs obtained from the patients with lipodystrophy are capable of being used. It will be very promising and realistic if this concept is applied to lipoatrophy; one form of lipodystrophies that deteriorates the patients’ quality of life because of excessive loss of soft tissue in the exposed areas such as face and extremities. Since lipodystrophy is frequently observed in the human immunodeficiency virus (HIV)-infected patients receiving highly active antiretroviral therapy (HAART), the present study aims to examine the biological potentials of ADSCs isolated from the HIV-infected patients with lipodystrophy associated with the HAART treatment. Growth properties, adipogenic differentiation, and mitochondrial reactive oxygen species (ROS) production were examined in ADSCs from HIV-infected and HIV-uninfected patients. Our results clearly demonstrated that ADSCs from both patients showed indistinguishable growth properties and potentials for adipocyte differentiation in vitro. Thus, although the number of cases were limited, ADSCs isolated from the patients with lipodystrophy retain sufficient physiological and biological activity for the reconstitution of adipose-tissue, suggesting that ADSCs from the patients with lipodystrophy could be used for autologous ADSC-based regenerative therapy.

scholarly journals Therapeutic potential of small extracellular vesicles derived from lipoma tissue in adipose tissue regeneration—an in vitro and in vivo study

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Pengyu Hong ◽  
Xiaoyang Xu ◽  
Xin Hu ◽  
Hao Yang ◽  
Yue Wu ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Extracellular Vesicles ◽  
Tissue Regeneration ◽  
Lipid Droplets ◽  
Adipogenic Differentiation ◽  
Rt Pcr ◽  
Oil Red O Staining ◽  
Oil Red O

Abstract Objective To explore the adipogenic effects of the small extracellular vesicles derived from the lipoma tissues (sEV-LT), and to find a new cell-free therapeutic approach for adipose tissue regeneration. Methods Adipose tissue-derived stem cells (ADSCs) and small extracellular vesicles derived from the adipose tissues (sEV-AT) were isolated from human adipose tissue, while sEV-LT were isolated from human lipomatous tissue. ADSCs were characterized by using flow cytometric analysis and adipogenic and osteogenic differentiation assays. sEV was identified by electron microscopy, nanoparticle tracking, and western blotting. ADSCs were treated with sEV-LT and sEV-AT, respectively. Fluorescence confocal microscopy was used to investigate whether sEV-LT and sEV-AT could be taken by ADSCs. The proliferation and migration abilities and adipogenic differentiation assay of ADSCs were evaluated by CCK-8 assays, scratch test, and oil red O staining test, and the expression levels of adipogenic-related genes C/EBP-δ, PPARγ2, and Adiponectin in ADSCs were assessed by real-time quantitative PCR (RT-PCR). The sEV-LT and sEV-AT transplantation tubes were implanted subcutaneously in SD rats, and the neotissues were qualitatively and histologically evaluated at 2, 4, 8, and 12 weeks after transplantation. Hematoxylin and eosin (H&E) staining was subsequently used to observe and compare the adipogenesis and angiogenesis in neotissues, while immunohistochemistry was used to examine the expression and the distribution of C/EBP-α, PPARγ, Adiponectin, and CD31 at the 4th week. Results The in vitro experiments showed that both sEV-LT and sEV-AT could be taken up by ADSCs via endocytosis. The scratch experiment and CCK-8 experiment showed that the migration area and proliferation number of ADSCs in sEV-LT group and sEV-AT group were significantly higher than those in the non-sEV group (p < 0.05). Compared with sEV-AT group, sEV-LT group had larger migration area and proliferation number of ADSCs (p < 0.05). Oil red O staining and RT-PCR experiments showed that, compared with the non-sEVs group, the lipid droplets and the mRNA expression levels of adipogenesis-related genes PPARγ2 and Adiponectin of ADSCs in sEV-LT group and sEV-AT group were significantly upregulated (p < 0.05); however, there was no statistical significance in the expression level of C/EBP-δ (p > 0.05). In addition, no significant difference in the amount of lipid droplets and adipogenesis-related genes between the sEV-LT groups and sEV-AT was seen (p > 0.05). At 2, 4, 8, and 12 weeks, the adipocyte area and the number of capillaries in neotissues in the sEV-LT groups and sEV-AT groups were significantly increased compared with the Matrigel group (p < 0.05); however, there was no dramatic difference between sEV-LT groups and sEV-AT groups (p > 0.05). At the 4th week, neotissues in the sEV-LT groups and sEV-AT groups all showed upregulated expression of C/EBP-α, PPARγ, Adiponectin, and CD31 protein, while neotissues in the Matrigel group only showed positive expression of CD31 protein. Conclusions This study demonstrated that sEV-LT exerted promotion effects on adipose tissue regeneration by accelerating the proliferation, migration, and adipogenic differentiation of ADSCs in vitro and recruiting adipocytes and promoting angiogenesis in vivo. The sEV-LT could serve as an alternative cell-free therapeutic strategy for generating adipose tissue, thus providing a promising application prospect in tissue engineering.

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