scholarly journals Role of FTO in Adipocyte Development and Function: Recent Insights

2015 ◽  
Vol 2015 ◽  
pp. 1-7 ◽  
Author(s):  
Myrte Merkestein ◽  
Dyan Sellayah
Keyword(s):  
Adipose Tissue ◽  
Genome Wide Association Study ◽  
Genome Wide ◽  
Adipose Tissue Development ◽  
Obesity Susceptibility ◽  
Mechanistic Basis ◽  
And Function ◽  
Adipocyte Development ◽  
Shed Light

In 2007,FTOwas identified as the first genome-wide association study (GWAS) gene associated with obesity in humans. Since then, various animal models have served to establish the mechanistic basis behind this association. Many earlier studies focussed on FTO’s effects on food intake via central mechanisms. Emerging evidence, however, implicates adipose tissue development and function in the causal relationship between perturbations in FTO expression and obesity. The purpose of this mini review is to shed light on these new studies of FTO function in adipose tissue and present a clearer picture of its impact on obesity susceptibility.

scholarly journals Vitamin D signalling in adipose tissue

2012 ◽  
Vol 108 (11) ◽  
pp. 1915-1923 ◽  
Author(s):  
Cherlyn Ding ◽  
Dan Gao ◽  
John Wilding ◽  
Paul Trayhurn ◽  
Chen Bing
Keyword(s):  
Vitamin D ◽  
Adipose Tissue ◽  
Vitamin D Deficiency ◽  
Vitamin D Metabolites ◽  
Hydroxyvitamin D ◽  
The Metabolic Syndrome ◽  
Prevalence Of Obesity ◽  
Adipose Tissue Development ◽  
And Function

Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function.

Latest advances in STAT signaling and function in adipocytes

2020 ◽  
Vol 134 (6) ◽  
pp. 629-639 ◽  
Author(s):  
Jasmine A. Burrell ◽  
Anik Boudreau ◽  
Jacqueline M. Stephens
Keyword(s):  
Adipose Tissue ◽  
Growth Factors ◽  
Immune Responses ◽  
Energy Homeostasis ◽  
Biological Processes ◽  
Mature Adipocyte ◽  
Adipose Tissue Development ◽  
And Function ◽  
Adipocyte Development ◽  
Stat Pathway

Abstract Adipocytes and adipose tissue are not inert and make substantial contributions to systemic metabolism by influencing energy homeostasis, insulin sensitivity, and lipid storage. In addition to well-studied hormones such as insulin, there are numerous hormones, cytokines, and growth factors that modulate adipose tissue function. Many endocrine mediators utilize the JAK–STAT pathway to mediate dozens of biological processes, including inflammation and immune responses. JAKs and STATs can modulate both adipocyte development and mature adipocyte function. Of the seven STAT family members, four STATs are expressed in adipocytes and regulated during adipogenesis (STATs 1, 3, 5A, and 5B). These STATs have been shown to play influential roles in adipose tissue development and function. STAT6, in contrast, is highly expressed in both preadipocytes and mature adipocytes, but is not considered to play a major role in regulating adipose tissue function. This review will summarize the latest research that pertains to the functions of STATs in adipocytes and adipose tissue.

scholarly journals Long non-coding RNAs in regulation of adipogenesis and adipose tissue function

eLife ◽  
2020 ◽  
Vol 9 ◽  
Author(s):  
Tiziana Squillaro ◽  
Gianfranco Peluso ◽  
Umberto Galderisi ◽  
Giovanni Di Bernardo
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Drug Targets ◽  
Metabolic Diseases ◽  
Tissue Development ◽  
Cellular Functions ◽  
Adipose Tissue Development ◽  
And Function

Complex interaction between genetics, epigenetics, environment, and nutrition affect the physiological activities of adipose tissues and their dysfunctions, which lead to several metabolic diseases including obesity or type 2 diabetes. Here, adipogenesis appears to be a process characterized by an intricate network that involves many transcription factors and long noncoding RNAs (lncRNAs) that regulate gene expression. LncRNAs are being investigated to determine their contribution to adipose tissue development and function. LncRNAs possess multiple cellular functions, and they regulate chromatin remodeling, along with transcriptional and post-transcriptional events; in this way, they affect gene expression. New investigations have demonstrated the pivotal role of these molecules in modulating white and brown/beige adipogenic tissue development and activity. This review aims to provide an update on the role of lncRNAs in adipogenesis and adipose tissue function to promote identification of new drug targets for treating obesity and related metabolic diseases.

scholarly journals Inflammation and JNK's Role in Niacin-GPR109A Diminished Flushed Effect in Microglial and Neuronal Cells With Relevance to Schizophrenia

2021 ◽  
Vol 12 ◽  
Author(s):  
Sabrina H. Ansarey
Keyword(s):  
Inflammatory Mediators ◽  
Neuronal Death ◽  
Microglial Activation ◽  
Negative Symptoms ◽  
Genome Wide Association Study ◽  
Genetic Mutation ◽  
Genome Wide ◽  
Ultra High Risk ◽  
Altered Proteins

Schizophrenia is a neuropsychiatric illness with no single definitive aetiology, making its treatment difficult. Antipsychotics are not fully effective because they treat psychosis rather than the cognitive or negative symptoms. Antipsychotics fail to alleviate symptoms when patients enter the chronic stage of illness. Topical application of niacin showed diminished skin flush in the majority of patients with schizophrenia compared to the general population who showed flushing. The niacin skin flush test is useful for identifying patients with schizophrenia at their ultra-high-risk stage, and understanding this pathology may introduce an effective treatment. This review aims to understand the pathology behind the diminished skin flush response, while linking it back to neurons and microglia. First, it suggests that there are altered proteins in the GPR109A-COX-prostaglandin pathway, inflammatory imbalance, and kinase signalling pathway, c-Jun N-terminal kinase (JNK), which are associated with diminished flush. Second, genes from the GPR109A-COX-prostaglandin pathway were matched against the 128-loci genome wide association study (GWAS) for schizophrenia using GeneCards, suggesting that G-coupled receptor-109A (GPR109A) may have a genetic mutation, resulting in diminished flush. This review also suggests that there may be increased pro-inflammatory mediators in the GPR109A-COX-prostaglandin pathway, which contributes to the diminished flush pathology. Increased levels of pro-inflammatory markers may induce microglial-activated neuronal death. Lastly, this review explores the role of JNK on pro-inflammatory mediators, proteins in the GPR109A-COX-prostaglandin pathway, microglial activation, and neuronal death. Inhibiting JNK may reverse the changes observed in the diminished flush response, which might make it a good therapeutic target.

scholarly journals Immune Checkpoints Expression in Chronic Lung Allograft Rejection

2021 ◽  
Vol 12 ◽  
Author(s):  
Ilaria Righi ◽  
Valentina Vaira ◽  
Letizia Corinna Morlacchi ◽  
Giorgio Alberto Croci ◽  
Valeria Rossetti ◽  
...  
Keyword(s):  
T Lymphocytes ◽  
Bronchiolitis Obliterans Syndrome ◽  
Immune Checkpoints ◽  
Hla Antibodies ◽  
Restrictive Allograft Syndrome ◽  
And Function ◽  
Shed Light

Chronic lung allograft dysfunction (CLAD) is the main cause of poor survival and low quality of life of lung transplanted patients. Several studies have addressed the role of dendritic cells, macrophages, T cells, donor specific as well as anti-HLA antibodies, and interleukins in CLAD, but the expression and function of immune checkpoint molecules has not yet been analyzed, especially in the two CLAD subtypes: BOS (bronchiolitis obliterans syndrome) and RAS (restrictive allograft syndrome). To shed light on this topic, we conducted an observational study on eight consecutive grafts explanted from patients who received lung re-transplantation for CLAD. The expression of a panel of immune molecules (PD1/CD279, PDL1/CD274, CTLA4/CD152, CD4, CD8, hFoxp3, TIGIT, TOX, B-Cell-Specific Activator Protein) was analyzed by immunohistochemistry in these grafts and in six control lungs. Results showed that RAS compared to BOS grafts were characterized by 1) the inversion of the CD4/CD8 ratio; 2) a higher percentage of T lymphocytes expressing the PD-1, PD-L1, and CTLA4 checkpoint molecules; and 3) a significant reduction of exhausted PD-1-expressing T lymphocytes (PD-1pos/TOXpos) and of exhausted Treg (PD-1pos/FOXP3pos) T lymphocytes. Results herein, although being based on a limited number of cases, suggest a role for checkpoint molecules in the development of graft rejection and offer a possible immunological explanation for the worst prognosis of RAS. Our data, which will need to be validated in ampler cohorts of patients, raise the possibility that the evaluation of immune checkpoints during follow-up offers a prognostic advantage in monitoring the onset of rejection, and suggest that the use of compounds that modulate the function of checkpoint molecules could be evaluated in the management of chronic rejection in LTx patients.

scholarly journals The FAM171A2 gene is a key regulator of progranulin expression and modifies the risk of multiple neurodegenerative diseases

2020 ◽  
Vol 6 (43) ◽  
pp. eabb3063
Author(s):  
Wei Xu ◽  
Si-Da Han ◽  
Can Zhang ◽  
Jie-Qiong Li ◽  
Yan-Jiang Wang ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Genome Wide Association Study ◽  
In Vitro Study ◽  
Genome Wide ◽  
A Genome ◽  
Increased Risk ◽  
Pathophysiological Role ◽  
Independent Cohort

Progranulin (PGRN) is a secreted pleiotropic glycoprotein associated with the development of common neurodegenerative diseases. Understanding the pathophysiological role of PGRN may help uncover biological underpinnings. We performed a genome-wide association study to determine the genetic regulators of cerebrospinal fluid (CSF) PGRN levels. Common variants in region of FAM171A2 were associated with lower CSF PGRN levels (rs708384, P = 3.95 × 10−12). This was replicated in another independent cohort. The rs708384 was associated with increased risk of Alzheimer’s disease, Parkinson’s disease, and frontotemporal dementia and could modify the expression of the FAM171A2 gene. FAM171A2 was considerably expressed in the vascular endothelium and microglia, which are rich in PGRN. The in vitro study further confirmed that the rs708384 mutation up-regulated the expression of FAM171A2, which caused a decrease in the PGRN level. Collectively, genetic, molecular, and bioinformatic findings suggested that FAM171A2 is a key player in regulating PGRN production.

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