Glucocorticoid hormones and energy homeostasis

2014 ◽  
Vol 19 (2) ◽  
Author(s):  
Roldan M. de Guia ◽  
Adam J. Rose ◽  
Stephan Herzig
Keyword(s):  
Energy Homeostasis ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Metabolic Dysfunction ◽  
Endocrine Control ◽  
Regulatory Pathways ◽  
Glucose And Lipid Metabolism ◽  
Steroid Binding

AbstractGlucocorticoids (GC) and their cognate intracellular receptor, the glucocorticoid receptor (GR), have been characterised as critical checkpoints in the endocrine control of energy homeostasis in mammals. Indeed, aberrant GC action has been linked to a variety of severe metabolic diseases, including obesity, insulin resistance and type 2 diabetes. As a steroid-binding member of the nuclear receptor superfamily of transcription factors, the GR translocates into the cell nucleus upon GC binding where it serves as a transcriptional regulator of distinct GC-responsive target genes that are – in many cases – associated with glucose and lipid regulatory pathways and thereby intricately control both physiological and pathophysiological systemic energy homeostasis. Here, we summarize the current knowledge of GC/GR function in energy metabolism and systemic metabolic dysfunction, particularly focusing on glucose and lipid metabolism.

scholarly journals Update on FXR Biology: Promising Therapeutic Target?

2018 ◽  
Vol 19 (7) ◽  
pp. 2069 ◽  
Author(s):  
Chang Han
Keyword(s):  
Therapeutic Target ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Farnesoid X Receptor ◽  
Metabolic Effects ◽  
Metabolic Dysfunction ◽  
Energy Status ◽  
Safety Issues ◽  
Attractive Therapeutic Target

Farnesoid X receptor (FXR), a metabolic nuclear receptor, plays critical roles in the maintenance of systemic energy homeostasis and the integrity of many organs, including liver and intestine. It regulates bile acid, lipid, and glucose metabolism, and contributes to inter-organ communication, in particular the enterohepatic signaling pathway, through bile acids and fibroblast growth factor-15/19 (FGF-15/19). The metabolic effects of FXR are also involved in gut microbiota. In addition, FXR has various functions in the kidney, adipose tissue, pancreas, cardiovascular system, and tumorigenesis. Consequently, the deregulation of FXR may lead to abnormalities of specific organs and metabolic dysfunction, allowing the protein as an attractive therapeutic target for the management of liver and/or metabolic diseases. Indeed, many FXR agonists have been being developed and are under pre-clinical and clinical investigations. Although obeticholic acid (OCA) is one of the promising candidates, significant safety issues have remained. The effects of FXR modulation might be multifaceted according to tissue specificity, disease type, and/or energy status, suggesting the careful use of FXR agonists. This review summarizes the current knowledge of systemic FXR biology in various organs and the gut–liver axis, particularly regarding the recent advancement in these fields, and also provides pharmacological aspects of FXR modulation for rational therapeutic strategies and novel drug development.

scholarly journals MicroRNAs in Obesity, Metabolic Syndrome and Diabetes Mellitus

2011 ◽  
Vol 3 (1) ◽  
pp. 4
Author(s):  
Anna Meiliana ◽  
Andi Wijaya
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Energy Homeostasis ◽  
Target Genes ◽  
Metabolic Diseases ◽  
Full Potential ◽  
Glucose And Lipid Metabolism ◽  
Small Regulatory Rnas ◽  
Novel Therapeutic Strategies ◽  
Novel Therapeutic

BACKGROUND: MicroRNAs (miRNAs) are small regulatory RNAs that play important roles in development of diseases. Several studies have provided evidences showing that miRNAs affect pathways that are fundamental for metabolic control in adipocyte and skeletal muscle differentiations. Some miRNAs have been implicated in lipid, amino acid, and glucose homeostasis. This leads to the possibility that miRNAs may contribute to common metabolic diseases and point to novel therapeutic opportunities based on targeting of miRNAs.CONTENT: miRNAs have been recognized as a class of epigenetic regulators of metabolism and energy homeostasis, primarily because the simultaneous regulation of a large number of target genes can be accomplished by a single miRNA. Emerging evidences suggest that miRNAs play a key role in the pathological development of obesity by affecting adipocyte differentiation. miRNAs have been implicated as novel protagonists in the pathogenesis of Diabetes Mellitus (DM), regulation of insulin production, secretion and action. They also appear to play a role in the development of diabetic complications such as nephropathy and cardiac hypertrophy.SUMMARY: Involvement of miRNAs in glucose and lipid metabolism has provided strong evidences to confirm their roles as key players in regulation of complex metabolic pathways. Additionally, it indicates potential outlook for novel therapeutic strategies in the management of obesity, metabolic syndrome and DM. Further research in this field is needed to ascertain the full potential of miRNAs as novel metabolic biomarkers and potent therapeutic agents against obesity and its metabolic disorders.KEYWORDS: obesity, metabolic syndrome, diabetes, miRNAs, adipogenesis, insulin, pancreatic cells

scholarly journals The Alterations in and the Role of the Th17/Treg Balance in Metabolic Diseases

2021 ◽  
Vol 12 ◽  
Author(s):  
Siwen Zhang ◽  
Xiaokun Gang ◽  
Shuo Yang ◽  
Mengzhao Cui ◽  
Lin Sun ◽  
...  
Keyword(s):  
Chronic Inflammation ◽  
Metabolic Diseases ◽  
Treg Cells ◽  
Metabolic Dysfunction ◽  
T Helper ◽  
T Helper 17 ◽  
Glucose And Lipid Metabolism ◽  
Underlying Mechanisms

Chronic inflammation plays an important role in the development of metabolic diseases. These include obesity, type 2 diabetes mellitus, and metabolic dysfunction-associated fatty liver disease. The proinflammatory environment maintained by the innate immunity, including macrophages and related cytokines, can be influenced by adaptive immunity. The function of T helper 17 (Th17) and regulatory T (Treg) cells in this process has attracted attention. The Th17/Treg balance is regulated by inflammatory cytokines and various metabolic factors, including those associated with cellular energy metabolism. The possible underlying mechanisms include metabolism-related signaling pathways and epigenetic regulation. Several studies conducted on human and animal models have shown marked differences in and the important roles of Th17/Treg in chronic inflammation associated with obesity and metabolic diseases. Moreover, Th17/Treg seems to be a bridge linking the gut microbiota to host metabolic disorders. In this review, we have provided an overview of the alterations in and the functions of the Th17/Treg balance in metabolic diseases and its role in regulating immune response-related glucose and lipid metabolism.

An Overview of FGF19 and FGF21: The Therapeutic Role in the Treatment of the Metabolic Disorders and Obesity

2018 ◽  
Vol 50 (06) ◽  
pp. 441-452 ◽  
Author(s):  
Nasim Babaknejad ◽  
Hashem Nayeri ◽  
Roohullah Hemmati ◽  
Somaye Bahrami ◽  
Ahmad Esmaillzadeh
Keyword(s):  
Cellular Proliferation ◽  
Metabolic Diseases ◽  
Glucose And Lipid Metabolism ◽  
Timely Review ◽  
Wide Range ◽  
Probable Role ◽  
Artery Disease ◽  
Treatment Of Obesity ◽  
The Relationship

AbstractFibroblast growth factors (FGFs) are responsible for the regulation of a wide range of biological functions, among which cellular proliferation, survival, migration, and differentiation could be pointed out. FGF19 controls the enterohepatic bile acid/cholesterol system, and FGF21 modulates fatty acid/glucose metabolism. Obesity, type 2 diabetes, coronary artery disease, and cancer, all can alter FGF21 circulating concentrations. In contrast to FGF21, metabolic diseases exhibit reduced serum FGF19 levels. Accordingly, FGF19 and FGF21 play important roles in regulating glucose and lipid metabolism. Hence, we present here a timely review on the relationship between FGF19/21 and metabolic diseases, especially obesity, and their probable role in development and treatment of obesity seems necessary.

scholarly journals Can Epigenetics of Endothelial Dysfunction Represent the Key to Precision Medicine in Type 2 Diabetes Mellitus?

2019 ◽  
Vol 20 (12) ◽  
pp. 2949 ◽  
Author(s):  
Celeste Coco ◽  
Luca Sgarra ◽  
Maria Assunta Potenza ◽  
Carmela Nacci ◽  
Barbara Pasculli ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Endothelial Dysfunction ◽  
Environmental Factors ◽  
Precision Medicine ◽  
Metabolic Diseases ◽  
Current Knowledge ◽  
Transcriptional Responses

In both developing and industrialized Countries, the growing prevalence of Type 2 Diabetes Mellitus (T2DM) and the severity of its related complications make T2DM one of the most challenging metabolic diseases worldwide. The close relationship between genetic and environmental factors suggests that eating habits and unhealthy lifestyles may significantly affect metabolic pathways, resulting in dynamic modifications of chromatin-associated proteins and homeostatic transcriptional responses involved in the progression of T2DM. Epigenetic mechanisms may be implicated in the complex processes linking environmental factors to genetic predisposition to metabolic disturbances, leading to obesity and type 2 diabetes mellitus (T2DM). Endothelial dysfunction represents an earlier marker and an important player in the development of this disease. Dysregulation of the endothelial ability to produce and release vasoactive mediators is recognized as the initial feature of impaired vascular activity under obesity and other insulin resistance conditions and undoubtedly concurs to the accelerated progression of atherosclerotic lesions and overall cardiovascular risk in T2DM patients. This review aims to summarize the most current knowledge regarding the involvement of epigenetic changes associated with endothelial dysfunction in T2DM, in order to identify potential targets that might contribute to pursuing “precision medicine” in the context of diabetic illness.

scholarly journals The Liver under the Spotlight: Bile Acids and Oxysterols as Pivotal Actors Controlling Metabolism

Cells ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 400
Author(s):  
Charlotte Lefort ◽  
Patrice D. Cani
Keyword(s):  
Bile Acids ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Inflammatory Diseases ◽  
Attractive Potential ◽  
Bioactive Lipids ◽  
Glucose And Lipid Metabolism ◽  
Long Time ◽  
New Treatments

Among the myriad of molecules produced by the liver, both bile acids and their precursors, the oxysterols are becoming pivotal bioactive lipids which have been underestimated for a long time. Their actions are ranging from regulation of energy homeostasis (i.e., glucose and lipid metabolism) to inflammation and immunity, thereby opening the avenue to new treatments to tackle metabolic disorders associated with obesity (e.g., type 2 diabetes and hepatic steatosis) and inflammatory diseases. Here, we review the biosynthesis of these endocrine factors including their interconnection with the gut microbiota and their impact on host homeostasis as well as their attractive potential for the development of therapeutic strategies for metabolic disorders.

Biological role of miRNA-146a at virus infections. Modern strategy of search of new safe pharmacological agents for treatment

2021 ◽  
Vol 19 (2) ◽  
pp. 145-174
Author(s):  
Petr D. Shabanov ◽  
Vladimir I. Vashchenko
Keyword(s):  
Virus Infection ◽  
Posttranscriptional Regulation ◽  
Target Genes ◽  
Viral Infections ◽  
Current Knowledge ◽  
Recipient Cell ◽  
Viral Disease ◽  
Cellular Mirnas ◽  
Specific Expression ◽  
Regulatory Pathways

Cellular microRNAs (miRNAs) were identified as a key player in the posttranscriptional regulation of cellular-genes regulatory pathways. Here, we review the current knowledge on the interaction between RNA viruses and cellular miRNAs. We also discuss how cell and tissue-specific expression of miRNAs can directly affect viral pathogenesis. They also emerged as a significant regulator of the immune response. In particular, miR-146a acts as an importance modulator of function and differentiation cells of the innate and adaptive immunity. It has been associated with disorder including cancer and viral infections. Given its significance in the regulation of key cellular processes, it is not surprising which virus infection have found ways to dysregulation of miRNAs. miR-146a has been identified in exosomes (exosomal miR-146a). After the exosomes release from donor cells, they are taken up by the recipient cell and probably the exosomal miR-146a is able to modulate the antiviral response in the recipient cell and result in making them more susceptible to virus infection. In this review, we discuss recent reports regarding miR-146a expression levels, target genes, function, and contributing role in the pathogenesis of the viral infection and provide a clue to develop the new preventive and therapeutic strategies for medical treatment viral disease, and СOVID-19.

scholarly journals You Are What You Eat—The Relationship between Diet, Microbiota, and Metabolic Disorders—A Review

Nutrients ◽  
2020 ◽  
Vol 12 (4) ◽  
pp. 1096 ◽  
Author(s):  
Małgorzata Moszak ◽  
Monika Szulińska ◽  
Paweł Bogdański
Keyword(s):  
Gut Microbiota ◽  
Metabolic Disorders ◽  
Energy Homeostasis ◽  
Current Knowledge ◽  
Vegetarian Diet ◽  
Bile Acid Metabolism ◽  
Glucose And Lipid Metabolism ◽  
Inflammatory Bowel ◽  
Major Factors ◽  
The Relationship

The gut microbiota (GM) is defined as the community of microorganisms (bacteria, archaea, fungi, viruses) colonizing the gastrointestinal tract. GM regulates various metabolic pathways in the host, including those involved in energy homeostasis, glucose and lipid metabolism, and bile acid metabolism. The relationship between alterations in intestinal microbiota and diseases associated with civilization is well documented. GM dysbiosis is involved in the pathogenesis of diverse diseases, such as metabolic syndrome, cardiovascular diseases, celiac disease, inflammatory bowel disease, and neurological disorders. Multiple factors modulate the composition of the microbiota and how it physically functions, but one of the major factors triggering GM establishment is diet. In this paper, we reviewed the current knowledge about the relationship between nutrition, gut microbiota, and host metabolic status. We described how macronutrients (proteins, carbohydrates, fat) and different dietary patterns (e.g., Western-style diet, vegetarian diet, Mediterranean diet) interact with the composition and activity of GM, and how gut bacterial dysbiosis has an influence on metabolic disorders, such as obesity, type 2 diabetes, and hyperlipidemia.

scholarly journals The Role of Adipose Tissue Mitochondria: Regulation of Mitochondrial Function for the Treatment of Metabolic Diseases

2019 ◽  
Vol 20 (19) ◽  
pp. 4924 ◽  
Author(s):  
Lee ◽  
Park ◽  
Oh ◽  
Lee ◽  
Kim ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Mitochondrial Function ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Oxidative Capacity ◽  
Adipose Tissues ◽  
Adaptive Thermogenesis ◽  
Brown Adipose

: Mitochondria play a key role in maintaining energy homeostasis in metabolic tissues, including adipose tissues. The two main types of adipose tissues are the white adipose tissue (WAT) and the brown adipose tissue (BAT). WAT primarily stores excess energy, whereas BAT is predominantly responsible for energy expenditure by non-shivering thermogenesis through the mitochondria. WAT in response to appropriate stimuli such as cold exposure and β-adrenergic agonist undergoes browning wherein it acts as BAT, which is characterized by the presence of a higher number of mitochondria. Mitochondrial dysfunction in adipocytes has been reported to have strong correlation with metabolic diseases, including obesity and type 2 diabetes. Dysfunction of mitochondria results in detrimental effects on adipocyte differentiation, lipid metabolism, insulin sensitivity, oxidative capacity, and thermogenesis, which consequently lead to metabolic diseases. Recent studies have shown that mitochondrial function can be improved by using thiazolidinedione, mitochondria-targeted antioxidants, and dietary natural compounds; by performing exercise; and by controlling caloric restriction, thereby maintaining the metabolic homeostasis by inducing adaptive thermogenesis of BAT and browning of WAT. In this review, we focus on and summarize the molecular regulation involved in the improvement of mitochondrial function in adipose tissues so that strategies can be developed to treat metabolic diseases.

scholarly journals The Roles and Pharmacological Effects of FGF21 in Preventing Aging-Associated Metabolic Diseases

2021 ◽  
Vol 8 ◽  
Author(s):  
Junbin Yan ◽  
Yunmeng Nie ◽  
Jielu Cao ◽  
Minmin Luo ◽  
Maoxiang Yan ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Cellular Aging ◽  
Fibroblast Growth Factor 21 ◽  
Aging Effects ◽  
Dark Cloud ◽  
Alcoholic Fatty Liver ◽  
Glucose And Lipid Metabolism ◽  
Theoretical Support

With the continuous improvement of living standards but the lack of exercise, aging-associated metabolic diseases such as obesity, type 2 diabetes mellitus (T2DM), and non-alcoholic fatty liver disease (NAFLD) are becoming a lingering dark cloud over society. Studies have found that metabolic disorders are near related to glucose, lipid metabolism, and cellular aging. Fibroblast growth factor 21 (FGF21), a member of the FGFs family, efficiently regulates the homeostasis of metabolism and cellular aging. By activating autophagy genes and improving inflammation, FGF21 indirectly delays cellular aging and directly exerts anti-aging effects by regulating aging genes. FGF21 can also regulate glucose and lipid metabolism by controlling metabolism-related genes, such as adipose triglyceride lipase (ATGL) and acetyl-CoA carboxylase (ACC1). Because FGF21 can regulate metabolism and cellular aging simultaneously, FGF21 analogs and FGF21 receptor agonists are gradually being valued and could become a treatment approach for aging-associated metabolic diseases. However, the mechanism by which FGF21 achieves curative effects is still not known. This review aims to interpret the interactive influence between FGF21, aging, and metabolic diseases and delineate the pharmacology of FGF21, providing theoretical support for further research on FGF21.

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