scholarly journals Activation of PPARs Modulates Signalling Pathways and Expression of Regulatory Genes in Osteoclasts Derived from Human CD14+ Monocytes

2019 ◽  
Vol 20 (7) ◽  
pp. 1798 ◽  
Author(s):  
Abe Kasonga ◽  
Marlena C. Kruger ◽  
Magdalena Coetzee
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Nuclear Factor Κb ◽  
The Body ◽  
Signalling Pathways ◽  
Peroxisome Proliferator ◽  
Ppar Γ ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors

Osteoclasts are the sole bone resorbing cell in the body and their over activity is key in the development of osteoporosis. Osteoclastogenesis is mediated by receptor activator of nuclear factor κB ligand (RANKL) signalling pathways. Unsaturated fatty acids (UFA) are known to inhibit osteoclastogenesis by targeting RANKL signalling. However, the mechanisms of action remain unclear. Peroxisome proliferator activated receptors (PPARs) are a family of nuclear receptors, with three known isoforms (PPAR-α, PPAR-β/δ and PPAR-γ), that are known to bind UFAs and are expressed in osteoclasts. In this study, we aimed to determine how different families of UFAs activate PPARs and how PPAR activation influences osteoclast signalling. Human CD14+ monocytes were seeded into cluster plates with RANKL and macrophage colony stimulating factor (M-CSF) in the presence of PPAR agonists or different types of UFAs. All the PPAR agonists were shown to upregulate the activity of their respective receptors. Polyunsaturated fatty acids increased PPAR-α to a greater extent than monounsaturated fatty acids (MUFAs), which favoured PPAR-β/δ activation. All PPAR agonists inhibited osteoclastogenesis. The activation of RANKL signalling pathways and expression of key osteoclast genes were downregulated by PPAR agonists. This study reveals that PPAR activation can inhibit osteoclastogenesis through modulation of RANKL signalling.

scholarly journals Hydroxy Monounsaturated Fatty Acids as Agonists for Peroxisome Proliferator-Activated Receptors

2010 ◽  
Vol 33 (5) ◽  
pp. 854-861 ◽  
Author(s):  
Hiroshi Yokoi ◽  
Hajime Mizukami ◽  
Akito Nagatsu ◽  
Hiroki Tanabe ◽  
Makoto Inoue
Keyword(s):  
Fatty Acids ◽  
Monounsaturated Fatty Acids ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptors

scholarly journals Treatment of Obesity-Related Complications with Novel Classes of Naturally Occurring PPAR Agonists

2011 ◽  
Vol 2011 ◽  
pp. 1-7 ◽  
Author(s):  
Josep Bassaganya-Riera ◽  
Amir J. Guri ◽  
Raquel Hontecillas
Keyword(s):  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
Peroxisome Proliferator ◽  
Punicic Acid ◽  
Ppar Γ ◽  
Naturally Occurring ◽  
Wide Range ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Treatment Of Obesity

The prevalence of obesity and its associated comorbidities has grown to epidemic proportions in the US and worldwide. Thus, developing safe and effective therapeutic approaches against these widespread and debilitating diseases is important and timely. Activation of peroxisome proliferator-activated receptors (PPARs) α, γ, and δ through several classes of pharmaceuticals can prevent or treat a variety of metabolic and inflammatory diseases, including type II diabetes (T2D). Thus, PPARs represent important molecular targets for developing novel and better treatments for a wide range of debilitating and widespread obesity-related diseases and disorders. However, available PPAR γ agonistic drugs such as Avandia have significant adverse side effects, including weight gain, fluid retention, hepatotoxicity, and congestive heart failure. An alternative to synthetic agonists of PPAR γ is the discovery and development of naturally occurring and safer nutraceuticals that may be dual or pan PPAR agonists. The purpose of this paper is to summarize the health effects of three plant-derived PPAR agonists: abscisic acid (ABA), punicic acid (PUA), and catalpic acid (CAA) in the prevention and treatment of chronic inflammatory and metabolic diseases and disorders.

scholarly journals Minireview: Challenges and Opportunities in Development of PPAR Agonists

2014 ◽  
Vol 28 (11) ◽  
pp. 1756-1768 ◽  
Author(s):  
Matthew B. Wright ◽  
Michele Bortolini ◽  
Moh Tadayyon ◽  
Martin Bopst
Keyword(s):  
Peroxisome Proliferator ◽  
Gene Promoters ◽  
Ppar Γ ◽  
Specific Target Gene ◽  
Challenges And Opportunities ◽  
Ppar Agonists ◽  
Peroxisome Proliferator Activated Receptors ◽  
Transcriptional Complex ◽  
Ppar Ligands ◽  
Coregulatory Proteins

The clinical impact of the fibrate and thiazolidinedione drugs on dyslipidemia and diabetes is driven mainly through activation of two transcription factors, peroxisome proliferator-activated receptors (PPAR)-α and PPAR-γ. However, substantial differences exist in the therapeutic and side-effect profiles of specific drugs. This has been attributed primarily to the complexity of drug-target complexes that involve many coregulatory proteins in the context of specific target gene promoters. Recent data have revealed that some PPAR ligands interact with other non-PPAR targets. Here we review concepts used to develop new agents that preferentially modulate transcriptional complex assembly, target more than one PPAR receptor simultaneously, or act as partial agonists. We highlight newly described on-target mechanisms of PPAR regulation including phosphorylation and nongenomic regulation. We briefly describe the recently discovered non-PPAR protein targets of thiazolidinediones, mitoNEET, and mTOT. Finally, we summarize the contributions of on- and off-target actions to select therapeutic and side effects of PPAR ligands including insulin sensitivity, cardiovascular actions, inflammation, and carcinogenicity.

Nutritional modulation of metabolic inflammation

2017 ◽  
Vol 45 (4) ◽  
pp. 979-985 ◽  
Author(s):  
Anna M. Kirwan ◽  
Yvonne M. Lenighan ◽  
Marcella E. O'Reilly ◽  
Fiona C. McGillicuddy ◽  
Helen M. Roche
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Insulin Signalling ◽  
Saturated Fatty Acids ◽  
Dietary Fats ◽  
Peroxisome Proliferator ◽  
Metabolic Inflammation ◽  
Inflammatory Pathways ◽  
Pyrin Domain ◽  
Peroxisome Proliferator Activated Receptors

Metabolic inflammation is a very topical area of research, wherein aberrations in metabolic and inflammatory pathways probably contribute to atherosclerosis, insulin resistance (IR) and type 2 diabetes. Metabolic insults arising from obesity promote inflammation, which in turn impedes insulin signalling and reverse cholesterol transport (RCT). Key cells in the process are metabolically activated macrophages, which up-regulate both pro- and anti-inflammatory pathways in response to lipid spillover from adipocytes. Peroxisome proliferator-activated receptors and AMP-activated protein kinase (AMPK) are regulators of cellular homeostasis that influence both inflammatory and metabolic pathways. Dietary fats, such as saturated fatty acids (SFAs), can differentially modulate metabolic inflammation. Palmitic acid, in particular, is a well-characterized nutrient that promotes metabolic inflammation via the NLRP3 (the nod-like receptor containing a pyrin domain) inflammasome, which is partly attributable to AMPK inhibition. Conversely, some unsaturated fatty acids are less potent agonists of metabolic inflammation. For example, monounsaturated fatty acid does not reduce AMPK as potently as SFA and n-3 polyunsaturated fatty acids actively resolve inflammation via resolvins and protectins. Nevertheless, the full extent to which nutritional state modulates metabolic inflammation requires greater clarification.

DEVELOPMENT OF AN EXPERIMENTAL MODEL OF AVITAMINOSIS F

2020 ◽  
Vol 20 (2) ◽  
pp. 38-40
Author(s):  
A. Levitsky ◽  
A. Lapinska ◽  
I. Selivanskaya
Keyword(s):  
Fatty Acids ◽  
Experimental Model ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Coconut Oil ◽  
The Body ◽  
Regulatory Function ◽  
Omega 3 ◽  
White Rats ◽  
Arachidonic Acids

The article analyzes the role of essential polyunsaturated fatty acids (PUFA), especially omega-3 series in humans and animals. The biosynthesis of essential PUFA in humans and animals is very limited, so they must be consumed with food (feed). Тhe ratio of omega-3 and omega-6 PUFA is very important. Biomembranes of animal cells contain about 30% PUFA with a ratio of ω-6/ ω-3 1-2. As this ratio increases, the physicochemical properties of biomembranes and the functional activity of their receptors change. The regulatory function of essential PUFA is that in the body under the action of oxygenase enzymes (cyclooxygenase, lipoxygenase) are formed extremely active hormone-like substances (eicosanoids and docosanoids), which affect a number of physiological processes: inflammation, immunity, metabolism. Moreover, ω-6 PUFA form eicosanoids, which have pro-inflammatory, immunosuppressive properties, and ω-3 PUFAs form eicosanoids and docosanoids, which have anti-inflammatory and immunostimulatory properties. Deficiency of essential PUFA, and especially ω-3 PUFA, leads to impaired development of the body and its state of health, which are manifestations of avitaminosis F. Prevention and treatment of avitaminosis F is carried out with drugs that contain PUFA. To create new, more effective vitamin F preparations, it is necessary to reproduce the model of vitamin F deficiency. An experimental model of vitamin F deficiency in white rats kept on a fat –free diet with the addition of coconut oil, which is almost completely free of unsaturated fatty acids, and saturated fatty acids make up almost 99 % of all fatty acids was developed. The total content of ω-6 PUFA (sum of linoleic and arachidonic acids), the content of ω-3 PUFA (α-linolenic, eicosapentaenoic and docosahexaenoic acids) in neutral lipids (triglycerides and cholesterol esters) defined. Тhe content of ω-6 PUFA under the influence of coconut oil decreased by 3.3 times, and the content of ω-3 PUFA - by 7.5 times. Тhe influence of coconut oil, the content of ω-6 PUFA decreased by 2.1 times, and the content of ω-3 PUFA - by 2.8 times. The most strongly reduces the content of ω-3 PUFA, namely eicosapentaenoic, coconut oil, starting from 5 %. Consumption of FFD with a content of 15 % coconut oil reduces the content of eicosapentaenoic acid to zero, ie we have an absolute deficiency of one of the most important essential PUFAs, which determined the presence of vitamin F deficiency.

USE OF ESSENTIAL FATTY ACIDS AND THEIR ROLE IN THE HUMAN ORGANISM DEVELOPMENT

2018 ◽  
Vol 28 (4) ◽  
pp. 1219-1225
Author(s):  
Filip Jovanovski ◽  
Toni Mitrovski ◽  
Viktorija Bezhovska
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
Essential Fatty Acids ◽  
Normal Growth ◽  
The Body ◽  
Human Nutrition ◽  
Human Organism ◽  
Working Ability ◽  
The World ◽  
Growth Development

Food is not just a pleasure in life, it is also an important factor for our health. Human nutrition is a mixture of nutrients, which are the only source of energy needed for survival. Energy-poor diet endangers many life functions, and above all the working ability. In the world, the meaning of the diet is very serious, and hence the demands for a –rational, healthy and safe diet are growing. Human nutrition contains saturated and unsaturated fatty acids. Essential fatty acids (EFAs) must be ingested in everyday diet because the body does not produce it. They are very important for human health. They are present in each cell of the human body and are an important factor for the normal growth, development and functioning of cells, muscles, nerves and organs. They are also used in the production of certain hormones - such as prostaglandins, which are crucial for the performance of certain important processes. The deficit from EFAs is due to a number of health problems, including more serious diseases.

New trends in the pharmacological intervention of PPARs in obesity: Role of natural and synthetic compounds_

2020 ◽  
Vol 28 ◽  
Author(s):  
Seyed Mohammad Nabavi ◽  
Kasi Pandima Devi ◽  
Sethuraman Sathya ◽  
Ana Sanches-Silva ◽  
Listos Joanna ◽  
...  
Keyword(s):  
Tissue Expression ◽  
Health Concern ◽  
Pharmacological Intervention ◽  
Peroxisome Proliferator ◽  
Expression Of Genes ◽  
Ppar Agonists ◽  
Prevalence Of Obesity ◽  
Peroxisome Proliferator Activated Receptors ◽  
Natural And Synthetic

: Obesity is a major health concern for a growing fraction of the population, with the prevalence of obesity and its related metabolic disorders not being fully understood. Over the last decade, many attempts have been undertaken to understand the mechanisms at the basis of this condition, in which the accumulation of fat occurring in adipose tissue, leads to the pathogenesis of obesity related disorders. Among the most recent studies, those on Peroxisome Proliferator Activated Receptors (PPARs) revealed that these nuclear receptor proteins acting as transcription factors, among others, regulate the expression of genes involved in energy, lipid, and glucose metabolisms, and chronic inflammation. The three different isotypes of PPARs, with different tissue expression and ligand binding specificity, exert similar or overlapping functions directly or indirectly linked to obesity. In this study, we reviewed the available scientific reports concerning the PPARs structure and functions, especially in obesity, considering both natural and synthetic ligands and their role in the therapy of obesity and obesity-associated disorders. In the whole, the collected data show that there are both natural and synthetic compounds that show beneficial promising activity as PPAR agonists in chronic diseases related to obesity.

Differential Effects of Dietary Fatty Acids on Body Composition and Adiposity

2020 ◽  
Vol 16 (2) ◽  
pp. 142-154 ◽  
Author(s):  
Hadi Emamat ◽  
Zahra Yari ◽  
Hossein Farhadnejad ◽  
Parvin Mirmiran
Keyword(s):  
Fatty Acids ◽  
Body Composition ◽  
Unsaturated Fatty Acids ◽  
Saturated Fatty Acids ◽  
Total Body Weight ◽  
Fat Distribution ◽  
Monounsaturated Fatty Acids ◽  
Dietary Fatty Acids ◽  
Dietary Fats ◽  
Total Body

Recent evidence has highlighted that fat accumulation, particularly abdominal fat distribution, is strongly associated with metabolic disturbance. It is also well-recognized that the metabolic responses to variations in macronutrients intake can affect body composition. Previous studies suggest that the quality of dietary fats can be considered as the main determinant of body-fat deposition, fat distribution, and body composition without altering the total body weight; however, the effects of dietary fats on body composition have controversial results. There is substantial evidence to suggest that saturated fatty acids are more obesogen than unsaturated fatty acids, and with the exception of some isomers like conjugate linoleic acid, most dietary trans fatty acids are adiposity enhancers, but there is no consensus on it yet. On the other hand, there is little evidence to indicate that higher intake of the n-3 and the n-6 polyunsaturated fatty acids can be beneficial in attenuating adiposity, and the effect of monounsaturated fatty acids on body composition is contradictory. Accordingly, the content of this review summarizes the current body of knowledge on the potential effects of the different types of dietary fatty acids on body composition and adiposity. It also refers to the putative mechanisms underlying this association and reflects on the controversy of this topic.

scholarly journals VITAL NEED OF THE BODY FOR CERTAIN UNSATURATED FATTY ACIDS

1932 ◽  
Vol 96 (1) ◽  
pp. 143-156
Author(s):  
Herbert M. Evans ◽  
Samuel Lepkovsky
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
The Body

scholarly journals VITAL NEED OF THE BODY FOR CERTAIN UNSATURATED FATTY ACIDS

1934 ◽  
Vol 106 (2) ◽  
pp. 445-450a
Author(s):  
Herbert M. Evans ◽  
Samuel Lepkovsky ◽  
Elizabeth A. Murphy
Keyword(s):  
Fatty Acids ◽  
Unsaturated Fatty Acids ◽  
The Body
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