scholarly journals The Intricate Role of p53 in Adipocyte Differentiation and Function

Cells ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. 2621
Author(s):  
Yun Kyung Lee ◽  
Yu Seong Chung ◽  
Ji Hye Lee ◽  
Jin Mi Chun ◽  
Jun Hong Park

For more than three decades, numerous studies have demonstrated the function of p53 in cell cycle, cellular senescence, autophagy, apoptosis, and metabolism. Among diverse functions, the essential role of p53 is to maintain cellular homeostatic response to stress by regulating proliferation and apoptosis. Recently, adipocytes have been studied with increasing intensity owing to the increased prevalence of metabolic diseases posing a serious public health concern and because metabolic dysfunction can directly induce tumorigenesis. The prevalence of metabolic diseases has steadily increased worldwide, and a growing interest in these diseases has led to the focus on the role of p53 in metabolism and adipocyte differentiation with or without metabolic stress. However, our collective understanding of the direct role of p53 in adipocyte differentiation and function remains insufficient. Therefore, this review focuses on the newly discovered roles of p53 in adipocyte differentiation and function.

2021 ◽  
Vol 22 (4) ◽  
pp. 1949
Author(s):  
Emma Wilkinson ◽  
Yan-Hong Cui ◽  
Yu-Ying He

RNA modifications are diverse post-transcriptional modifications that regulate RNA metabolism and gene expression. RNA modifications, and the writers, erasers, and readers that catalyze these modifications, serve as important signaling machineries in cellular stress responses and disease pathogenesis. In response to stress, RNA modifications are mobilized to activate or inhibit the signaling pathways that combat stresses, including oxidative stress, hypoxia, therapeutic stress, metabolic stress, heat shock, DNA damage, and ER stress. The role of RNA modifications in response to these cellular stressors is context- and cell-type-dependent. Due to their pervasive roles in cell biology, RNA modifications have been implicated in the pathogenesis of different diseases, including cancer, neurologic and developmental disorders and diseases, and metabolic diseases. In this review, we aim to summarize the roles of RNA modifications in molecular and cellular stress responses and diseases.


Molecules ◽  
2021 ◽  
Vol 26 (3) ◽  
pp. 682
Author(s):  
Serena Coppola ◽  
Carmen Avagliano ◽  
Antonio Calignano ◽  
Roberto Berni Canani

Worldwide obesity is a public health concern that has reached pandemic levels. Obesity is the major predisposing factor to comorbidities, including type 2 diabetes, cardiovascular diseases, dyslipidemia, and non-alcoholic fatty liver disease. The common forms of obesity are multifactorial and derive from a complex interplay of environmental changes and the individual genetic predisposition. Increasing evidence suggest a pivotal role played by alterations of gut microbiota (GM) that could represent the causative link between environmental factors and onset of obesity. The beneficial effects of GM are mainly mediated by the secretion of various metabolites. Short-chain fatty acids (SCFAs) acetate, propionate and butyrate are small organic metabolites produced by fermentation of dietary fibers and resistant starch with vast beneficial effects in energy metabolism, intestinal homeostasis and immune responses regulation. An aberrant production of SCFAs has emerged in obesity and metabolic diseases. Among SCFAs, butyrate emerged because it might have a potential in alleviating obesity and related comorbidities. Here we reviewed the preclinical and clinical data that contribute to explain the role of butyrate in this context, highlighting its crucial contribute in the diet-GM-host health axis.


2021 ◽  
Vol 12 ◽  
Author(s):  
Diego Catalán ◽  
Miguel Andrés Mansilla ◽  
Ashley Ferrier ◽  
Lilian Soto ◽  
Kristine Oleinika ◽  
...  

Regulatory B cells (Bregs) is a term that encompasses all B cells that act to suppress immune responses. Bregs contribute to the maintenance of tolerance, limiting ongoing immune responses and reestablishing immune homeostasis. The important role of Bregs in restraining the pathology associated with exacerbated inflammatory responses in autoimmunity and graft rejection has been consistently demonstrated, while more recent studies have suggested a role for this population in other immune-related conditions, such as infections, allergy, cancer, and chronic metabolic diseases. Initial studies identified IL-10 as the hallmark of Breg function; nevertheless, the past decade has seen the discovery of other molecules utilized by human and murine B cells to regulate immune responses. This new arsenal includes other anti-inflammatory cytokines such IL-35 and TGF-β, as well as cell surface proteins like CD1d and PD-L1. In this review, we examine the main suppressive mechanisms employed by these novel Breg populations. We also discuss recent evidence that helps to unravel previously unknown aspects of the phenotype, development, activation, and function of IL-10-producing Bregs, incorporating an overview on those questions that remain obscure.


2014 ◽  
Vol 995 ◽  
pp. 1-27 ◽  
Author(s):  
Mahbuba Rahman ◽  
M. Rubayet Hasan

Pentose phosphate (PP) pathway, which is ubiquitously present in all living organisms, is one of the major metabolic pathways associated with glucose metabolism. The most important functions of this pathway includes the generation of reducing equivalents in the form of NADPH for reductive biosynthesis, and production of ribose sugars for the biosynthesis of nucleotides, amino acids, and other macromolecules required by all living cells. Under normal conditions of growth, PP pathway is important for cell cycle progression, myelin formation, and the maintenance of the structure and function of brain, liver, cortex and other organs. Under diseased conditions, such as in cases of many metabolic, neurological or malignant diseases, pathological mechanisms augment due to defects in the PP pathway genes. Adoption of alternative metabolic pathways by cells that are metabolically abnormal, or malignant cells that are resistant to chemotherapeutic drugs often plays important roles in disease progression and severity. Accordingly, the PP pathway has been suggested to play critical roles in protecting cancer or abnormal cells by providing reduced environment, to protect cells from oxidative damage and generating structural components for nucleic acids biosynthesis. Novel drugs that targets one or more components of the PP pathway could potentially serve to overcome challenges associated with currently available therapeutic options for many metabolic and non-metabolic diseases. However, careful designing of drugs is critical that takes into the accounts of cell’s broader genomic, proteomic and metabolic contexts under consideration, in order to avoid undesirable side-effects. In this review, we discuss the role of PP pathway under normal and abnormal physiological conditions and the potential of the PP pathway as a target for new drug development to treat metabolic and non-metabolic diseases.


2022 ◽  
pp. 212-229
Author(s):  
Ashfaq Ahmad Shah ◽  
Sumaira Qayoom ◽  
Amit Gupta ◽  
Aqueel Ur Rehman

Current research on phytochemicals is mainly focused on novel phenolic and polyphenolic compounds expressing their potential as therapeutic agents in various diseases like cancer, autoimmune diseases, cardiovascular disorders, diabetes, oxidative stress-related diseases, as well as their properties to inhibit the growth and proliferation of infectious agents. Among the human physiological disorders, one of the most severe endocrine metabolic diseases is Diabetes mellitus which is a clinical disease distinguished by a deficit in the production of insulin or resistance to the action of insulin. Globally, diabetes is an increasing health concern which is now emerging as an epidemic. About 700-800 plants are exhibiting anti-diabetic activity that has been studied. As far as nanotechnology in diabetes research is concerned, it has made possible the buildout of novel glucose measurement as well as insulin delivery modalities that possess the potential to excellently enhance the quality of life of the diabetic patient.


2004 ◽  
Vol 8 (2) ◽  
pp. 90-96 ◽  
Author(s):  
Aton M. Holzer ◽  
Richard D. Granstein

Background: The nucleotide adenosine triphosphate (ATP) has long been known to drive and participate in countless intracellular processes. Extracellular ATP and its metabolite adenosine have also been shown to exert a variety of effects on nearly every cell type in human skin. Knowledge of the sources and effects of extracellular ATP in human skin may help shape new therapies for skin injury, inflammation, and numerous other cutaneous disorders. Objective: The objective of this review is to introduce the reader to current knowledge regarding the sources and effects of extracellular ATP in human skin and to outline areas in which further research is necessary to clarify the nature and mechanism of these effects. Conclusion: Extracellular ATP seems to play a direct role in triggering skin inflammatory, regenerative, and fibrotic responses to mechanical injury, an indirect role in melanocyte proliferation and apoptosis, and a complex role in Langerhans cell-directed adaptive immunity.


Biochimie ◽  
2005 ◽  
Vol 87 (1) ◽  
pp. 21-25 ◽  
Author(s):  
S Laitinen ◽  
C Fontaine ◽  
JC Fruchart ◽  
B Staels

2019 ◽  
Vol 3 (Supplement_1) ◽  
Author(s):  
Yan Qin Tan ◽  
Lai Kwok Leung

Abstract Objectives The objective of the present study is to elucidate the role of Transient Receptor Potential (TRP) channels in the process of adipogenesis and diabetes mellitus, in hopes of getting more understanding of the role of TRP channels in the process as well as in hopes of discovering a novel therapeutic target against metabolic diseases. Methods The role of TRP channels in adipogenesis and diabetes mellitus was investigated by using in vivo (C57/BL6J mice) and in vitro (3T3-L1 cells). The expressions of TRP isoforms were studied by using RT-PCR and western blotting assay. TRP channels agonist and antagonist were used to study the role of TRP channels while fat accumulation in cells was visualized by Oil Red O staining. Intracellular calcium inflow was estimated by confocal microscopy. Results Among the TRP channels screened, the authors identified the differential expressions of TRPC isoforms by using in vivo model. The results were further confirmed by using western blotting analysis. The changes in expression suggested the importance of the specific isoforms in the adipogenesis process. The agonist-antagonist study illustrated that the treatment of TRPC antagonists induced the maturation process while TRPC agonist attenuated adipocyte differentiation of 3T3-L1 cells. Conclusions The present study serves to illustrate the role of TRP channels in adipocyte biology. In conclusion, the current study demonstrated that the TRPC isoforms have differential expression during the maturation process of fat. Further, the modulation of TRPC could affect the adipocyte differentiation of 3T3-L1 cells. The understanding of TRPC channels in adipocyte biology serves as a novel therapeutic target against metabolic diseases such as obesity and diabetes mellitus. Funding Sources The research is funded by The Chinese University of Hong Kong Direct Grant. Supporting Tables, Images and/or Graphs


2013 ◽  
Vol 2013 ◽  
pp. 1-7 ◽  
Author(s):  
Hyun-Ae Seo ◽  
In-Kyu Lee

Metabolic diseases, such as type 2 diabetes and obesity, are increasing globally, and much work has been performed to elucidate the regulatory mechanisms of these diseases. Nuclear factor E2-related factor 2 (Nrf2) is a basic leucine zipper transcription factor that serves as a primary cellular defense against the cytotoxic effects of oxidative stress. Recent studies have proposed a close relationship between oxidative stress and energy metabolism-associated disease. The Nrf2 pathway, as a master regulator of cellular defense against oxidative stress, has emerged as a critical target of energy metabolism; however, its effects are controversial. This review examines the current state of research on the role of Nrf2 on energy metabolism, specifically with respect to its participation in adipocyte differentiation, obesity, and insulin resistance, and discusses the possibility of using Nrf2 as a therapeutic target in the clinic.


2018 ◽  
Vol 20 (1) ◽  
pp. 26 ◽  
Author(s):  
Jin Choi ◽  
No-Joon Song ◽  
A Lee ◽  
Dong Lee ◽  
Min-Ju Seo ◽  
...  

The phytochemical oxyresveratrol has been shown to exert diverse biological activities including prevention of obesity. However, the exact reason underlying the anti-obese effects of oxyresveratrol is not fully understood. Here, we investigated the effects and mechanism of oxyresveratrol in adipocytes and high-fat diet (HFD)-fed obese mice. Oxyresveratrol suppressed lipid accumulation and expression of adipocyte markers during the adipocyte differentiation of 3T3-L1 and C3H10T1/2 cells. Administration of oxyresveratrol in HFD-fed obese mice prevented body-weight gains, lowered adipose tissue weights, improved lipid profiles, and increased glucose tolerance. The anti-obese effects were linked to increases in energy expenditure and higher rectal temperatures without affecting food intake, fecal lipid content, and physical activity. The increased energy expenditure by oxyresveratrol was concordant with the induction of thermogenic genes including Ucp1, and the reduction of white adipocyte selective genes in adipose tissue. Furthermore, Foxo3a was identified as an oxyresveratrol-induced gene and it mimicked the effects of oxyresveratrol for induction of thermogenic genes and suppression of white adipocyte selective genes, suggesting the role of Foxo3a in oxyresveratrol-mediated anti-obese effects. Taken together, these data show that oxyresveratrol increases energy expenditure through the induction of thermogenic genes in adipose tissue and further implicates oxyresveratrol as an ingredient and Foxo3a as a molecular target for the development of functional foods in obesity and metabolic diseases.


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