scholarly journals Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways

2020 ◽  
Vol 21 (12) ◽  
pp. 4283 ◽  
Author(s):  
Melvin A. Ambele ◽  
Priyanka Dhanraj ◽  
Rachel Giles ◽  
Michael S. Pepper
Keyword(s):  
Adipose Tissue ◽  
Transcription Factors ◽  
Signalling Pathways ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Therapeutic Approaches ◽  
Molecular Determinants ◽  
Anatomical Localization ◽  
Two Phases

The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte commitment. Conversely, over a dozen molecular players including transcription factors, genes, signalling pathways, epigenetic regulators, and microRNAs have been described to be involved in the differentiation of preadipocytes to adipocytes; however, only peroxisome proliferator-activated receptor gamma has proven to be clinically relevant. A detailed understanding of how the molecular players underpinning adipogenesis relate to adipose tissue function could provide new therapeutic approaches for addressing obesity without compromising adipose tissue function.

scholarly journals Evidence for the Regulatory Role of Lipocalin 2 in High-Fat Diet-Induced Adipose Tissue Remodeling in Male Mice

Endocrinology ◽  
2013 ◽  
Vol 154 (10) ◽  
pp. 3525-3538 ◽  
Author(s):  
Hong Guo ◽  
Merlijn Bazuine ◽  
Daozhong Jin ◽  
Merry M. Huang ◽  
Samuel W. Cushman ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
High Fat Diet ◽  
Adipocyte Differentiation ◽  
Tissue Remodeling ◽  
Peroxisome Proliferator ◽  
Lipocalin 2 ◽  
Peroxisome Proliferator Activated Receptor ◽  
Adipose Tissue Remodeling ◽  
Fat Depot

Lipocalin 2 (Lcn2) has previously been characterized as an adipokine/cytokine playing a role in glucose and lipid homeostasis. In this study, we investigate the role of Lcn2 in adipose tissue remodeling during high-fat diet (HFD)-induced obesity. We find that Lcn2 protein is highly abundant selectively in inguinal adipose tissue. During 16 weeks of HFD feeding, the inguinal fat depot expanded continuously, whereas the expansion of the epididymal fat depot was reduced in both wild-type (WT) and Lcn2−/− mice. Interestingly, the depot-specific effect of HFD on fat mass was exacerbated and appeared more pronounced and faster in Lcn2−/− mice than in WT mice. In Lcn2−/− mice, adipocyte hypertrophy in both inguinal and epididymal adipose tissue was more profoundly induced by age and HFD when compared with WT mice. The expression of peroxisome proliferator-activated receptor-γ protein was significantly down-regulated, whereas the gene expression of extracellular matrix proteins was up-regulated selectively in epididymal adipocytes of Lcn2−/− mice. Consistent with these observations, collagen deposition was selectively higher in the epididymal, but not in the inguinal adipose depot of Lcn2−/− mice. Administration of the peroxisome proliferator-activated receptor-γ agonist rosiglitazone (Rosi) restored adipogenic gene expression. However, Lcn2 deficiency did not alter the responsiveness of adipose tissue to Rosi effects on the extracellular matrix expression. Rosi treatment led to the further enlargement of adipocytes with improved metabolic activity in Lcn2−/− mice, which may be associated with a more pronounced effect of Rosi treatment in reducing TGF-β in Lcn2−/− adipose tissue. Consistent with these in vivo observations, Lcn2 deficiency reduces the adipocyte differentiation capacity of stromal-vascular cells isolated from HFD-fed mice in these cells. Herein Rosi treatment was again able to stimulate adipocyte differentiation to a similar extent in WT and Lcn2−/− inguinal and epididymal stromal-vascular cells. Thus, combined, our data indicate that Lcn2 has a depot-specific role in HFD-induced adipose tissue remodeling.

scholarly journals INDUCTION OF BROWN ADIPOSE TISSUE: A REVIEW

2018 ◽  
Vol 11 (5) ◽  
pp. 472
Author(s):  
Ivo Romauld Sagayaraj ◽  
Akilashree S ◽  
Brindha Devi P
Keyword(s):  
Adipose Tissue ◽  
Brown Adipose Tissue ◽  
Secreted Proteins ◽  
Peroxisome Proliferator ◽  
Basic Study ◽  
Peroxisome Proliferator Activated Receptor ◽  
Efficient Treatment ◽  
Major Health ◽  
Brown Adipose

Objective: Obesity is the major problem which may lead to many other health ailments such as atherosclerosis, stroke, and depression. Both the cause as well as the treatment lies in the adipose tissue. The two main adipocytes, white adipose tissue (WAT) and brown adipose tissue (BAT) are responsible for the accumulation of fat and transformation of fat into heat, respectively. This review discusses the induction of BAT and browning of WAT by different pathways and activators to decrease the rate of obesity. Methods: Understanding the regulators, activators and secreted proteins which induce browning of WAT to BAT, as the BAT engage in thermogenesis process and transform fat into heat rather than storing it (WAT). Some of the core regulators are peroxisome proliferator-activated receptor-γ, PRDM16, PGC-1α. Results: A basic study explained about the origin of BAT and its functions, the function of hormones in BAT growth and its regulations. These studies provided the platform to understand about the mechanism of regulators, activators and secreted proteins which help in treating obesity and its related disorders by inducing the amount of BAT. Conclusion: The major health ailments caused by obesity can be reduced by increasing the activity of BAT and transforming WAT into BAT. A challenging way to treat these ailments is by regulating the activators and hormones responsible for the induction of BAT, so it transforms the excess fat into heat and avoiding the accumulation of fat. By understanding the role of regulators in the adipose tissue can provide various methods to reduce the chance of obesity and enhance efficient treatment in both children and adults.

scholarly journals Adipogenesis and lipotoxicity: role of peroxisome proliferator-activated receptor γ (PPARγ) and PPARγcoactivator-1 (PGC1)

2007 ◽  
Vol 10 (10A) ◽  
pp. 1132-1137 ◽  
Author(s):  
Gema Medina-Gomez ◽  
Sarah Gray ◽  
Antonio Vidal-Puig
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Peroxisome Proliferator ◽  
Metabolic Complications ◽  
Peroxisome Proliferator Activated Receptor ◽  
Toxic Response ◽  
Increased Risk ◽  
And Function

AbstractObesity is characterised by an increase in the adipose deposits, resulting from an imbalance between food intake and energy expenditure. When expansion of the adipose tissue reaches its maximum limit, as in obesity, fat accumulates in non-adipose tissues such as liver, heart, muscle and pancreas, developing a toxic response known as lipotoxicity, a condition that promotes the development of insulin resistance and other metabolic complications. Thus, the lipotoxic state may contribute to the increased risk of insulin resistance, diabetes, fatty liver and cardiovascular complications associated with obesity.We are interested in studying adipose tissue, specifically how mechanisms of adipogenesis and remodelling of adipose tissue, in terms of size and function of the adipocytes, could be considered a strategy to increase the capacity for lipid storage and prevent lipotoxicity. The peroxisome proliferator-activated receptors (PPARs) are a family of transcription factors that regulate energy balance by promoting either energy deposition or energy dissipation. Under normal physiological conditions, PPARγ is mainly expressed in adipose tissue and regulates diverse functions such as the development of fat cells and their capacity to store lipids. The generation of PPARγ knockout mice, either tissue specific or isoform specific, has provided new models to study PPARγ’s role in adipose tissue differentiation and function and have highlighted the essential role of PPARγ in adipogenesis and lipogenesis.A second strategy to prevent lipotoxicity is to increase the capacity of tissues to oxidise fatty acids. PPARγcoactivator-1α is a coactivator of PPARγ that induces the expression of genes that promote the differentiation of preadipocytes to brown adipocytes. Recently, it has been implicated in increasing the oxidation of fatty acids via increasing mitochondrial capacity and function, making this co-factor a key candidate for the treatment of lipotoxicity.

scholarly journals The Role of ATF-2 Family Transcription Factors in Adipocyte Differentiation: Antiobesity Effects of p38 Inhibitors

2009 ◽  
Vol 30 (3) ◽  
pp. 613-625 ◽  
Author(s):  
Toshio Maekawa ◽  
Wanzhu Jin ◽  
Shunsuke Ishii
Keyword(s):  
Transcription Factors ◽  
Adipocyte Differentiation ◽  
Physiological Role ◽  
Bone Morphogenetic Protein 2 ◽  
Peroxisome Proliferator ◽  
Necrosis Factor Alpha ◽  
Peroxisome Proliferator Activated Receptor ◽  
P38 Inhibitor ◽  
Morphogenetic Protein

ABSTRACT ATF-2 is a member of the ATF/CREB family of transcription factors and is activated by stress-activated protein kinases, such as p38. To analyze the physiological role of ATF-2 family transcription factors, we have generated mice with mutations in Atf-2 and Cre-bpa, an Atf-2-related gene. The trans-heterozygotes of both mutants were lean and had reduced white adipose tissue (WAT). ATF-2 and CRE-BPa were required for bone morphogenetic protein 2 (BMP-2)-and p38-dependent induction of peroxisome proliferator-activated receptor γ2 (PPARγ2), a key transcription factor mediating adipocyte differentiation. Since stored fat supplies have been recognized as a possible target for antiobesity treatments, we tested whether inhibition of the p38-ATF-2 pathway suppresses adipocyte differentiation and leads to reduced WAT by treating mice with a p38 inhibitor for long periods of time. High-fat diet (HFD)-induced obesity was significantly reduced in mice fed the p38 inhibitor. Furthermore, the p38 inhibitor alleviated HFD-induced insulin resistance. In p38 inhibitor-treated mice, macrophage infiltration into WAT was reduced and the tumor necrosis factor alpha (TNF-α) levels were lower than control mice. Thus, p38 inhibitors may provide a novel antiobesity treatment.

scholarly journals Molecular and cellular mechanisms of adipogenesis

2015 ◽  
Vol 18 (2) ◽  
pp. 12-19 ◽  
Author(s):  
Alexander Dmitrievich Egorov ◽  
Dmitry Nikolaevich Penkov ◽  
Vsevolod Arsen'evich Tkachuk
Keyword(s):  
Metabolic Syndrome ◽  
Adipose Tissue ◽  
Transcription Factors ◽  
Drug Targets ◽  
Adenosine Monophosphate ◽  
Endocrine Function ◽  
Peroxisome Proliferator ◽  
Cellular Mechanisms ◽  
Peroxisome Proliferator Activated Receptor ◽  
The Impact

The main components of metabolic syndrome include insulin resistance, hypertriglyceridemia and arterial hypertension. Obesity is the cause of metabolic syndrome, mainly as a consequence of the endocrine function of adipose tissue. The volume of adipose tissue depends on the size of individual adipocytes and on their number. The number of adipocytes increases as a result of enhanced adipocyte differentiation. The transcriptional cascade that regulates this differentiation has been well studied. The major adipogenic transcription factor peroxisome proliferator-activated receptor gamma is a ligand-activated nuclear receptor with essential roles in adipogenesis. Its ligands are used to treat metabolic syndrome and type 2 diabetes mellitus. . The present article describes the basic molecular and cellular mechanisms of adipogenesis and discusses the impact of insulin, glucocorticoids, cyclic adenosine monophosphate-activating agents, nuclear receptors and transcription factors on the process of adipogenesis. New regulatory regions of the genome that are capable of binding multiple transcription factors are described, and the most promising drug targets for the treatment of metabolic syndrome and obesity, including the homeodomain proteins Pbx1 and Prep1, are discussed..

scholarly journals Role of Peroxisome Proliferator-Activated Receptor Gamma and Its Ligands in the Treatment of Hematological Malignancies

PPAR Research ◽  
2008 ◽  
Vol 2008 ◽  
pp. 1-18 ◽  
Author(s):  
Tatiana M. Garcia-Bates ◽  
Geniece M. Lehmann ◽  
Patricia J. Simpson-Haidaris ◽  
Steven H. Bernstein ◽  
Patricia J. Sime ◽  
...  
Keyword(s):  
Immune Cells ◽  
Hematological Malignancies ◽  
Malignant Cell ◽  
Cellular Growth ◽  
Peroxisome Proliferator ◽  
Therapeutic Approaches ◽  
Peroxisome Proliferator Activated Receptor ◽  
New Therapeutic Approaches ◽  
Leukemias And Lymphomas

Peroxisome proliferator-activated receptor gamma (PPARγ) is a multifunctional transcription factor with important regulatory roles in inflammation, cellular growth, differentiation, and apoptosis. PPARγis expressed in a variety of immune cells as well as in numerous leukemias and lymphomas. Here, we review recent studies that provide new insights into the mechanisms by which PPARγligands influence hematological malignant cell growth, differentiation, and survival. Understanding the diverse properties of PPARγligands is crucial for the development of new therapeutic approaches for hematological malignancies.

Constitutive activation of p46JNK2 is indispensable for C/EBPδ induction in the initial stage of adipogenic differentiation

2017 ◽  
Vol 474 (20) ◽  
pp. 3421-3437 ◽  
Author(s):  
Joji Kusuyama ◽  
Tomokazu Ohnishi ◽  
Kenjiro Bandow ◽  
Muhammad Subhan Amir ◽  
Kaori Shima ◽  
...  
Keyword(s):  
Transcription Factors ◽  
Energy Homeostasis ◽  
Early Stage ◽  
Adipogenic Differentiation ◽  
Endocrine System ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Initial Stage

Adipogenic differentiation plays a vital role in energy homeostasis and endocrine system. Several transcription factors, including peroxisome proliferator-activated receptor gamma 2 and CCAAT–enhancer-binding protein (C/EBP) α, β, and δ, are important for the process, whereas the stage-specific intracellular signal transduction regulating the onset of adipogenesis remains enigmatic. Here, we explored the functional role of c-jun N-terminal kinases (JNKs) in adipogenic differentiation using in vitro differentiation models of 3T3-L1 cells and primary adipo-progenitor cells. JNK inactivation with either a pharmacological inhibitor or JNK2-specific siRNA suppressed adipogenic differentiation, characterized by decreased lipid droplet appearance and the down-regulation of Adiponectin, fatty acid protein 4 (Fabp4), Pparg2, and C/ebpa expressions. Conversely, increased adipogenesis was observed by the inducible overexpression of p46JNK2 (JNK2-1), whereas it was not observed by that of p54JNK2 (JNK2-2), indicating a distinct role of p46JNK2. The essential role of JNK appears restricted to the early stage of adipogenic differentiation, as JNK inhibition in the later stages did not influence adipogenesis. Indeed, JNK phosphorylation was significantly induced at the onset of adipogenic differentiation. As for the transcription factors involved in early adipogenesis, JNK inactivation significantly inhibited the induction of C/ebpd, but not C/ebpb, during the initial stage of adipogenic differentiation. JNK activation increased C/ebpd mRNA and protein expression through the induction and phosphorylation of activating transcription factor 2 (ATF2) that binds to a responsive element within the C/ebpd gene promoter region. Taken together, these data indicate that constitutive JNK activity is specifically required for the initial stage differentiation events of adipocytes.

Transcriptional dysregulation in Huntington’s Disease. The role in pathogenesis and potency for pharmacological targeting.

2020 ◽  
Vol 27 ◽  
Author(s):  
Aleksandra Pogoda ◽  
Natalia Chmielewska ◽  
Piotr Maciejak ◽  
Janusz Szyndler
Keyword(s):  
Transcription Factor ◽  
Transcription Factors ◽  
Huntington's Disease ◽  
Huntington’S Disease ◽  
Neurodegenerative Disorder ◽  
Regulatory Protein ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Molecular Manipulation

: Huntington’s disease (HD) is an inherited neurodegenerative disorder caused by a mutation in the gene that encodes a critical cell regulatory protein, huntingtin (Htt). The expansion of cytosine-adenine-guanine (CAG) trinucleotide repeats causes improper folding of functional proteins and is an initial trigger of pathological changes in the brain. Recent research has indicated that the functional dysregulation of many transcription factors underlies the neurodegenerative processes that accompany HD. These disturbances are caused not only by the loss of wild-type Htt (WT Htt) function but also by the occurrence of abnormalities that result from the action of mutant Htt (mHtt). In this review, we aim to describe the role of transcription factors that are currently thought to be strongly associated with HD pathogenesis, namely, RE1-silencing transcription factor, also known as neuron-restrictive silencer factor (REST/NRSF), forkhead box proteins (FOXPs), peroxisome proliferator-activated receptor gamma coactivator-1a (PGC1α), heat shock transcription factor 1 (HSF1), and nuclear factor κ light-chain-enhancer of activated B cells (NF-κB). We also take into account the role of these factors in the phenotype of HD as well as potential pharmacological interventions targeting the analyzed proteins. Furthermore, we considered whether molecular manipulation resulting in changes in transcription factor function may have clinical potency for treating HD.

scholarly journals Adipocyte-Specific ACKR3 Regulates Lipid Levels in Adipose Tissue

Biomedicines ◽  
2021 ◽  
Vol 9 (4) ◽  
pp. 394
Author(s):  
Selin Gencer ◽  
Yvonne Döring ◽  
Yvonne Jansen ◽  
Soyolmaa Bayasgalan ◽  
Olga Schengel ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Metabolic Diseases ◽  
Cholesterol Content ◽  
Metabolic Effects ◽  
Peroxisome Proliferator ◽  
Lipid Levels ◽  
Peroxisome Proliferator Activated Receptor ◽  
Ppar Γ ◽  
Deficient Mice

Dysfunctional adipose tissue (AT) may contribute to the pathology of several metabolic diseases through altered lipid metabolism, insulin resistance, and inflammation. Atypical chemokine receptor 3 (ACKR3) expression was shown to increase in AT during obesity, and its ubiquitous elimination caused hyperlipidemia in mice. Although these findings point towards a role of ACKR3 in the regulation of lipid levels, the role of adipocyte-specific ACKR3 has not yet been studied exclusively in this context. In this study, we established adipocyte- and hepatocyte-specific knockouts of Ackr3 in ApoE-deficient mice in order to determine its impact on lipid levels under hyperlipidemic conditions. We show for the first time that adipocyte-specific deletion of Ackr3 results in reduced AT triglyceride and cholesterol content in ApoE-deficient mice, which coincides with increased peroxisome proliferator-activated receptor-γ (PPAR-γ) and increased Angptl4 expression. The role of adipocyte ACKR3 in lipid handling seems to be tissue-specific as hepatocyte ACKR3 deficiency did not demonstrate comparable effects. In summary, adipocyte-specific ACKR3 seems to regulate AT lipid levels in hyperlipidemic Apoe−/− mice, which may therefore be a significant determinant of AT health. Further studies are needed to explore the potential systemic or metabolic effects that adipocyte ACKR3 might have in associated disease models.

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