scholarly journals Lipid Chaperones and Metabolic Inflammation

2011 ◽  
Vol 2011 ◽  
pp. 1-12 ◽  
Author(s):  
Masato Furuhashi ◽  
Shutaro Ishimura ◽  
Hideki Ota ◽  
Tetsuji Miura
Keyword(s):  
Large Body ◽  
Metabolic Stress ◽  
Fatty Acid Binding Proteins ◽  
Low Grade ◽  
Oxygen Species ◽  
Fatty Acid Binding ◽  
Metabolic Inflammation ◽  
The Past ◽  
Inflammatory State

Over the past decade, a large body of evidence has emerged demonstrating an integration of metabolic and immune response pathways. It is now clear that obesity and associated disorders such as insulin resistance and type 2 diabetes are associated with a metabolically driven, low-grade, chronic inflammatory state, referred to as “metaflammation.” Several inflammatory cytokines as well as lipids and metabolic stress pathways can activate metaflammation, which targets metabolically critical organs and tissues including adipocytes and macrophages to adversely affect systemic homeostasis. On the other hand, inside the cell, fatty acid-binding proteins (FABPs), a family of lipid chaperones, as well as endoplasmic reticulum (ER) stress, and reactive oxygen species derived from mitochondria play significant roles in promotion of metabolically triggered inflammation. Here, we discuss the molecular and cellular basis of the roles of FABPs, especially FABP4 and FABP5, in metaflammation and related diseases including obesity, diabetes, and atherosclerosis.

scholarly journals Estrogen Signaling in Metabolic Inflammation

2014 ◽  
Vol 2014 ◽  
pp. 1-20 ◽  
Author(s):  
Rosário Monteiro ◽  
Diana Teixeira ◽  
Conceição Calhau
Keyword(s):  
Visceral Obesity ◽  
Estrogen Signaling ◽  
Low Grade ◽  
Metabolic Inflammation ◽  
Inflammatory State ◽  
Inflammatory Processes ◽  
Prevalence Of Obesity ◽  
Research Questions ◽  
Metabolic Dysfunctions

There is extensive evidence supporting the interference of inflammatory activation with metabolism. Obesity, mainly visceral obesity, is associated with a low-grade inflammatory state, triggered by metabolic surplus where specialized metabolic cells such as adipocytes activate cellular stress initiating and sustaining the inflammatory program. The increasing prevalence of obesity, resulting in increased cardiometabolic risk and precipitating illness such as cardiovascular disease, type 2 diabetes, fatty liver, cirrhosis, and certain types of cancer, constitutes a good example of this association. The metabolic actions of estrogens have been studied extensively and there is also accumulating evidence that estrogens influence immune processes. However, the connection between these two fields of estrogen actions has been underacknowledged since little attention has been drawn towards the possible action of estrogens on the modulation of metabolism through their anti-inflammatory properties. In the present paper, we summarize knowledge on the modification inflammatory processes by estrogens with impact on metabolism and highlight major research questions on the field. Understanding the regulation of metabolic inflammation by estrogens may provide the basis for the development of therapeutic strategies to the management of metabolic dysfunctions.

scholarly journals The role of specific chaperons in pathogenesis of obesity and related diseases

2012 ◽  
Vol 58 (4) ◽  
pp. 48-53
Author(s):  
O V Vasiukova ◽  
P L Okorokov
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Saturated Fatty Acids ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Binding ◽  
Metabolic Inflammation ◽  
Protein Transporters

Obesity, type 2 diabetes mellitus, and atherosclerosis are associated with the development of "metabolic" inflammation. The proinflammatory mechanisms in adipocytes and macrophages are initiated by both extracellular mediators (cytokines, saturated fatty acids) and intracellular processes (endoplasmic reticulum stress, excessive production of free radicals). An important role in the development of "metabolic" inflammation is played by protein transporters of fatty acids ("fatty acid-binding proteins").

Abstract 1319: Plasma Levels of Fatty Acid Binding Proteins 4 and 5 are Markers of Adiposity and the Metabolic Syndrome but are not Independent Predictors of Subclinical Atherosclerosis in Type 2 Diabetes

Circulation ◽  
2007 ◽  
Vol 116 (suppl_16) ◽  
Author(s):  
Roshanak Bagheri ◽  
Michael Lehrke ◽  
Shiv Kapoor ◽  
Megan Wolfe ◽  
Karen Terembula ◽  
...  
Keyword(s):  
Risk Factors ◽  
Metabolic Syndrome ◽  
Fatty Acid ◽  
Subclinical Atherosclerosis ◽  
Fatty Acid Binding Proteins ◽  
Tobit Regression ◽  
Fatty Acid Binding ◽  
The Metabolic Syndrome ◽  
Type 2 Dm

Objectives: Adipocyte-fatty acid binding protein (aP2) or FABP4 is expressed predominantly in adipose and macrophages. Its less abundant family member, FABP5 (Mal1), is more diffusely expressed but also found in adipocytes and macrophages. Gene deletion studies in rodents suggest that FABP4, to a greater extent than FABP5, modulates obesity and atherosclerosis. Preliminary clinical studies support a relationship of circulating FABP4 with obesity and the metabolic syndrome (MetSyn). However, there are no studies of circulating FABPs and atherosclerosis in humans. Methods: We evaluated the association of FABP4 and 5 (ELISA, Biovender) with cardiovascular risk factors, NCEP-defined MetSyn and Coronary Artery Calcification (CAC) in 846 asymptomatic, type 2 DM subjects (62.5% Caucasian, 32.5% African-American; 60% male; aged 58.6±9.2) recruited to the Penn Diabetes Heart Study. Findings : Levels [(median (IQ range)] of FABP4 [37.1 (23.0–55.2) vs 20.9 (14.0–31.0) ng/mL; p<0.001] and FABP5 [1.5 (1.2–1.9) vs 1.4 (1.1–1.8) ng/mL; p<0.01] were higher in women than men. FABP4 was significantly correlated with waist circumference (r=0.4, p<0.001), levels of leptin (r=0.5, p<0.001), insulin (r=0.21, p<0.001), hsCRP (r=0.23, p<0.001), triglycerides (r=0.25, p<0.001) and inversely with HDL cholesterol (women r=−0.23, p<0.001; men r=−0.11, p<0.05). Plasma FABP5 had similar, but weaker biomarker correlations. Both were strongly associated with MetSyn (FABP4 χ 2 =29.8, p<0.0001; FABP5 χ 2 =36.2, p<0.0001). Notably, FABP4 [22.7 (15.0–35.9) vs 34.4 (22.9–55.0), p<0.001], but not FABP5 (p<0.89), levels were lower in subjects on thiazolidinedione therapy. In tobit regression, FABP4, but not FABP5, levels above the median were associated with CAC scores after adjustment for age, gender and ethnicity [1.68 (1.05–2.66), Ratio (CI), p<0.03] but this was attenuated after further adjusting for BMI and established risk factors [1.52 (0.49–2.48), Ratio (CI), p<0.09]. Conclusion: Both FABP 4 and 5 are biomarkers of adiposity and MetSyn. In the first study of its kind, plasma FABP4, but not FABP5, was associated with CAC in type 2 DM, but neither were independent predictors of this subclinical atherosclerosis measure.

scholarly journals Omega-3 fatty acids transport through the placenta

2016 ◽  
Vol 2 (1) ◽  
pp. 1-8
Author(s):  
Ariful Islam ◽  
Takanori Kodama ◽  
Yui Yamamoto ◽  
Majid Ebrahimi ◽  
Hirofumi Miyazaki ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Placental Transfer ◽  
Fatty Acid Binding Proteins ◽  
Fatty Acid Transport ◽  
Omega 3 ◽  
Fatty Acid Binding ◽  
Membrane Bound ◽  
Fatty Acid Transport Proteins

The placenta is a temporary vital organ for sustaining the development of the fetus throughout gestation. Although the fatty acid composition delivered to the fetus is largely determined by maternal circulating levels, the placenta preferentially transfers physiologically important long-chain polyunsaturated fatty acids (LC-PUFAs), particularly omega-3 (n-3) FAs. The precise mechanisms governing these transfers were covered in a veil, but have started to be revealed gradually. Several evidences suggest fatty acid transport proteins (FATPs), placental specific membrane bound fatty acid binding proteins (pFABPpm) and fatty acid translocases (FAT/CD36) involved in LC-PUFAs uptake. Our studies have shown that the placental transfer of omega-3 FAs through the trophoblast cells is largely contributed by fatty acid binding protein 3 (FABP3). Recently there are considerable interests in the potential for dietary omega-3 FAs as a therapeutic intervention for fetal disorders. In fact, prenatal supply of omega-3 FAs is essential for brain and retinal development. Recent findings suggest a potential opportunity of omega-3 FA interventions to decrease the incidence of type 2 diabetes in future generations. In this review, we discuss the molecular mechanism of transportation of omega-3 FAs through the placenta and how omega-3 FAs deficiency/supplementation impact on fetal development.Asian J. Med. Biol. Res. March 2016, 2(1): 1-8

scholarly journals The Essential Element Manganese, Oxidative Stress, and Metabolic Diseases: Links and Interactions

2018 ◽  
Vol 2018 ◽  
pp. 1-11 ◽  
Author(s):  
Longman Li ◽  
Xiaobo Yang
Keyword(s):  
Oxidative Stress ◽  
Metabolic Diseases ◽  
Essential Element ◽  
Ros Generation ◽  
Oxygen Species ◽  
Mitochondrial Oxidative Stress ◽  
Nonalcoholic Fatty Liver ◽  
The Past ◽  
The Relationship

Manganese (Mn) is an essential element that is involved in the synthesis and activation of many enzymes and in the regulation of the metabolism of glucose and lipids in humans. In addition, Mn is one of the required components for Mn superoxide dismutase (MnSOD) that is mainly responsible for scavenging reactive oxygen species (ROS) in mitochondrial oxidative stress. Both Mn deficiency and intoxication are associated with adverse metabolic and neuropsychiatric effects. Over the past few decades, the prevalence of metabolic diseases, including type 2 diabetes mellitus (T2MD), obesity, insulin resistance, atherosclerosis, hyperlipidemia, nonalcoholic fatty liver disease (NAFLD), and hepatic steatosis, has increased dramatically. Previous studies have found that ROS generation, oxidative stress, and inflammation are critical for the pathogenesis of metabolic diseases. In addition, deficiency in dietary Mn as well as excessive Mn exposure could increase ROS generation and result in further oxidative stress. However, the relationship between Mn and metabolic diseases is not clear. In this review, we provide insights into the role Mn plays in the prevention and development of metabolic diseases.

scholarly journals Hypertension and Erectile Dysfunction: Breaking Down the Challenges

2020 ◽  
Author(s):  
Amanda Almeida de Oliveira ◽  
Kenia Pedrosa Nunes
Keyword(s):  
Erectile Dysfunction ◽  
Innate Immune System ◽  
Innate Immune ◽  
Low Grade ◽  
Oxygen Species ◽  
Toll Like Receptor ◽  
Toll Like Receptor 4 ◽  
Corpora Cavernosa ◽  
Inflammatory State ◽  
Antioxidant Mechanisms

Abstract A diagnostic of hypertension increases the risk of erectile dysfunction (ED); likewise, ED can be an early sign of hypertension. In both cases, there is evidence that endothelial dysfunction is a common link between the 2 conditions. During hypertension, the sustained and widespread release of procontractile factors (e.g., angiotensin II, endothelin 1, and aldosterone) impairs the balance between vasoconstrictors and vasodilators and, in turn, detrimentally impacts vascular and erectile structures. This prohypertensive state associates with an enhancement in the generation of reactive oxygen species, which is not compensated by internal antioxidant mechanisms. Recently, the innate immune system, mainly via Toll-like receptor 4, has also been shown to actively contribute to the pathophysiology of hypertension and ED not only by inducing oxidative stress but also by sustaining a low-grade inflammatory state. Furthermore, some drugs used to treat hypertension can cause ED and, consequently, reduce compliance with the prescribed pharmacotherapy. To break down these challenges, in this review, we focus on discussing the well-established as well as the emerging mechanisms linking hypertension and ED with an emphasis on the signaling network of the vasculature and corpora cavernosa, the vascular-like structure of the penis.

Metabolic Syndrome and Its Effect on the Brain: Possible Mechanism

2018 ◽  
Vol 17 (8) ◽  
pp. 595-603 ◽  
Author(s):  
Nurul ‘Ain Arshad ◽  
Teoh Seong Lin ◽  
Mohamad Fairuz Yahaya
Keyword(s):  
Diabetes Mellitus ◽  
Metabolic Syndrome ◽  
Neurodegenerative Diseases ◽  
Disease Type ◽  
Low Grade ◽  
Oxygen Species ◽  
Metabolic Factors ◽  
Low Grade Inflammation ◽  
The Brain

Background & Objective: Metabolic syndrome (MetS) is an interconnected group of physiological, biochemical, clinical and metabolic factors that directly increase the risk of cardiovascular disease, type 2 diabetes mellitus (T2DM) and mortality. Rising evidence suggests that MetS plays a significant role in the progression of Alzheimer’s disease and other neurodegenerative diseases. Nonetheless, the factors linking this association has not yet been elucidated. As we are facing an increasing incidence of obesity and T2DM in all stages of life, understanding the association of MetS and neurodegenerative diseases is crucial to lessen the burden of the disease. Conclusion: In this review, we will discuss the possible mechanisms which may relate the association between MetS and cognitive decline which include vascular damages, elevation of reactive oxygen species (ROS), insulin resistance and low-grade inflammation.

scholarly journals Computational Tools in the Discovery of FABP4 Ligands: A Statistical and Molecular Modeling Approach

2019 ◽  
Author(s):  
Giuseppe Floresta ◽  
Davide Gentile ◽  
Giancarlo Perrini ◽  
Vincenzo Patamia ◽  
Antonio Rescifina
Keyword(s):  
Fatty Acid Binding Protein ◽  
Metabolic Diseases ◽  
New Drugs ◽  
Computational Tools ◽  
Computer Aided Drug Design ◽  
Fatty Acid Binding ◽  
Beneficial Effects ◽  
Acid Binding Protein ◽  
The Past

Small molecule inhibitors of adipocyte fatty-acid binding protein 4 (FABP4) have got interest following the recent publication of their pharmacologically beneficial effects. Recently it comes out that FABP4 is an attractive molecular target for the treatment of type 2 diabetes, other metabolic diseases, and some type of cancers. In the past years, hundreds of effective FABP4 inhibitors have been synthesized and discovered but, unfortunately, none of them is in the clinical research phase. The field of computer-aided drug design seems to be promising and useful for the identification of FABP4 inhibitors; hence, different structure- and ligand-based computational approaches were already performed for their identification. In this paper, we searched for new potentially active FABP4 ligands in the Marine Natural Products (MNP) database. 14,492 compounds were retrieved from this database and filtered through a statistical and computational filter. Seven compounds were suggested by our methodology to possess a potential inhibitory activity upon FABP4 in the range of 79&ndash;245 nM. ADMET properties prediction were performed to validate the hypothesis of the interaction with the intended target and to assess the drug-likeness of these derivatives; from these analyses, three molecules resulted as excellent candidates for becoming new drugs.

scholarly journals Cardiac Autonomic Neuropathy: A Progressive Consequence of Chronic Low-Grade Inflammation in Type 2 Diabetes and Related Metabolic Disorders

2020 ◽  
Vol 21 (23) ◽  
pp. 9005
Author(s):  
Nour-Mounira Z. Bakkar ◽  
Haneen S. Dwaib ◽  
Souha Fares ◽  
Ali H. Eid ◽  
Yusra Al-Dhaheri ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Autonomic Neuropathy ◽  
Experimental Models ◽  
Cardiac Autonomic Neuropathy ◽  
Low Grade ◽  
Metabolic Inflammation ◽  
The Metabolic Syndrome ◽  
Cardiovascular Morbidity And Mortality

Cardiac autonomic neuropathy (CAN) is one of the earliest complications of type 2 diabetes (T2D), presenting a silent cause of cardiovascular morbidity and mortality. Recent research relates the pathogenesis of cardiovascular disease in T2D to an ensuing chronic, low-grade proinflammatory and pro-oxidative environment, being the hallmark of the metabolic syndrome. Metabolic inflammation emerges as adipose tissue inflammatory changes extending systemically, on the advent of hyperglycemia, to reach central regions of the brain. In light of changes in glucose and insulin homeostasis, dysbiosis or alteration of the gut microbiome (GM) emerges, further contributing to inflammatory processes through increased gut and blood–brain barrier permeability. Interestingly, studies reveal that the determinants of oxidative stress and inflammation progression exist at the crossroad of CAN manifestations, dictating their evolution along the natural course of T2D development. Indeed, sympathetic and parasympathetic deterioration was shown to correlate with markers of adipose, vascular, and systemic inflammation. Additionally, evidence points out that dysbiosis could promote a sympatho-excitatory state through differentially affecting the secretion of hormones and neuromodulators, such as norepinephrine, serotonin, and γ-aminobutyric acid, and acting along the renin–angiotensin–aldosterone axis. Emerging neuronal inflammation and concomitant autophagic defects in brainstem nuclei were described as possible underlying mechanisms of CAN in experimental models of metabolic syndrome and T2D. Drugs with anti-inflammatory characteristics provide potential avenues for targeting pathways involved in CAN initiation and progression. The aim of this review is to delineate the etiology of CAN in the context of a metabolic disorder characterized by elevated oxidative and inflammatory load.

Gut microbiota in health and disease: an overview focused on metabolic inflammation

2016 ◽  
Vol 7 (2) ◽  
pp. 181-194 ◽  
Author(s):  
R. Nagpal ◽  
M. Kumar ◽  
A.K. Yadav ◽  
R. Hemalatha ◽  
H. Yadav ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Adverse Outcomes ◽  
Special Focus ◽  
Low Grade ◽  
Immune Functions ◽  
Metabolic Inflammation

In concern to the continuously rising global prevalence of obesity, diabetes and associated diseases, novel preventive and therapeutic approaches are urgently required. However, to explore and develop such innovative strategies, a meticulous comprehension of the biological basis of these diseases is extremely important. Past decade has witnessed an enormous amount of research investigation and advancement in the field of obesity, diabetes and metabolic syndrome, with the gut microbiota receiving a special focus in the triangle of nutrition, health and diseases. In particular, the role of gut microbiota in health and diseases has been one of the most vigorous and intriguing field of recent research; however, much still remains to be elucidated about its precise role in host metabolism and immune functions and its implication in the onset, progression as well as in the amelioration of metabolic ailments. Recent investigations have suggested a significant contribution of the gut microbiota in the regulation and impairment of energy homeostasis, thereby causing metabolic disorders, such as metabolic endotoxemia, insulin resistance and type 2 diabetes. Numerous inflammatory biomarkers have been found to be associated with obesity, diabetes and risk of other associated adverse outcomes, thereby suggesting that a persistent low-grade inflammatory response is a potential risk factor. In this milieu, this review intends to discuss potential evidences supporting the disturbance of the gut microbiota balance and the intestinal barrier permeability as a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.

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