scholarly journals The Impact of Ghrelin in Metabolic Diseases: An Immune Perspective

2017 ◽  
Vol 2017 ◽  
pp. 1-15 ◽  
Author(s):  
Jéssica Aparecida da Silva Pereira ◽  
Felipe Corrêa da Silva ◽  
Pedro Manoel Mendes de Moraes-Vieira
Keyword(s):  
Immune Cells ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Low Grade ◽  
Growth Hormone Secretagogue Receptor ◽  
Growth Hormone Secretagogue ◽  
Increased Risk ◽  
Inflammatory Profile ◽  
The Impact

Obesity and insulin resistance have reached epidemic proportions. Obesogenic conditions are associated with increased risk for the development of other comorbidities and obesity-related diseases. In metabolic disorders, there is chronic low-grade inflammation induced by the activation of immune cells, especially in metabolic relevant organs such as white adipose tissue (WAT). These immune cells are regulated by environmental and systemic cues. Ghrelin is a peptide secreted mainly by X/A-like gastric cells and acts through the growth hormone secretagogue receptor (GHS-R). This receptor is broadly expressed in the central nervous system (CNS) and in several cell types, including immune cells. Studies show that ghrelin induces an orexigenic state, and there is increasing evidence implicating an immunoregulatory role for ghrelin. Ghrelin mainly acts on the innate and adaptive immune systems to suppress inflammation and induce an anti-inflammatory profile. In this review, we discuss the immunoregulatory roles of ghrelin, the mechanisms by which ghrelin acts and potential pharmacological applications for ghrelin in the treatment of obesity-associated inflammatory diseases, such as type 2 diabetes (T2D).

scholarly journals Adipocyte, Immune Cells, and miRNA Crosstalk: A Novel Regulator of Metabolic Dysfunction and Obesity

Cells ◽  
2021 ◽  
Vol 10 (5) ◽  
pp. 1004
Author(s):  
Sonia Kiran ◽  
Vijay Kumar ◽  
Santosh Kumar ◽  
Robert L Price ◽  
Udai P. Singh
Keyword(s):  
Insulin Resistance ◽  
Immune Response ◽  
T Cells ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Liver Disorder ◽  
Low Grade ◽  
Peripheral Tissues ◽  
Nonalcoholic Fatty Liver ◽  
Cytokines And Chemokines

Obesity is characterized as a complex and multifactorial excess accretion of adipose tissue (AT) accompanied with alterations in the immune response that affects virtually all age and socioeconomic groups around the globe. The abnormal accumulation of AT leads to several metabolic diseases, including nonalcoholic fatty liver disorder (NAFLD), low-grade inflammation, type 2 diabetes mellitus (T2DM), cardiovascular disorders (CVDs), and cancer. AT is an endocrine organ composed of adipocytes and immune cells, including B-Cells, T-cells and macrophages. These immune cells secrete various cytokines and chemokines and crosstalk with adipokines to maintain metabolic homeostasis and low-grade chronic inflammation. A novel form of adipokines, microRNA (miRs), is expressed in many developing peripheral tissues, including ATs, T-cells, and macrophages, and modulates the immune response. miRs are essential for insulin resistance, maintaining the tumor microenvironment, and obesity-associated inflammation (OAI). The abnormal regulation of AT, T-cells, and macrophage miRs may change the function of different organs including the pancreas, heart, liver, and skeletal muscle. Since obesity and inflammation are closely associated, the dysregulated expression of miRs in inflammatory adipocytes, T-cells, and macrophages suggest the importance of miRs in OAI. Therefore, in this review article, we have elaborated the role of miRs as epigenetic regulators affecting adipocyte differentiation, immune response, AT browning, adipogenesis, lipid metabolism, insulin resistance (IR), glucose homeostasis, obesity, and metabolic disorders. Further, we will discuss a set of altered miRs as novel biomarkers for metabolic disease progression and therapeutic targets for obesity.

scholarly journals The role of selected mechanisms of innate immunity in the pathogenesis of diabetes

2021 ◽  
Vol 11 (9) ◽  
pp. 544-549
Author(s):  
Paulina Trojanowska ◽  
Magdalena Chrościńska-Krawczyk ◽  
Alina Trojanowska ◽  
Ewa Tywanek ◽  
Jakub Wronecki ◽  
...  
Keyword(s):  
Innate Immunity ◽  
Metabolic Diseases ◽  
Inflammatory Diseases ◽  
The Body ◽  
Low Grade ◽  
Intracellular Space ◽  
Cytoplasmic Proteins

Understanding the important role of the non-specific immune response in protecting the body against the development of numerous diseases has become partially possible after the discovery of several classes of pattern recognition receptors (PRR), such as Toll-like or NOD-like receptors. A group of cytoplasmic proteins called the inflammasome, which detect PAMP and DAMP through the PRR receptors, is able to activate pro-inflammatory cytokines and trigger an acute inflammatory reaction both in the extracellular and intracellular space. Low-grade systemic and local inflammation contributes to the development and progression of various conditions, including autoimmune and metabolic diseases, such as diabetes, metabolic syndrome and atherosclerosis, which until recently were not even considered inflammatory diseases. This review will discuss the role of innate immunity in the development of type 1 and type 2 diabetes, focusing on the role of specific innate immunity receptors and insulin resistance involved in these diseases pathogenesis.

scholarly journals Probiotic Lactobacillus fermentum strain JDFM216 improves cognitive behavior and modulates immune response with gut microbiota

2020 ◽  
Vol 10 (1) ◽  
Author(s):  
Mi Ri Park ◽  
Minhye Shin ◽  
Daye Mun ◽  
Seong-Yeop Jeong ◽  
Do-Youn Jeong ◽  
...  
Keyword(s):  
Gut Microbiota ◽  
Immune Cells ◽  
Metabolic Diseases ◽  
Wheel Running ◽  
Treated Group ◽  
Probiotic Bacterium ◽  
Lactobacillus Fermentum ◽  
Cognitive Behavior ◽  
Aged Mice ◽  
The Impact

AbstractIncreasing evidence indicates that alterations in gut microbiota are associated with mammalian development and physiology. The gut microbiota has been proposed as an essential player in metabolic diseases including brain health. This study aimed to determine the impact of probiotics on degenerative changes in the gut microbiota and cognitive behavior. Assessment of various behavioral and physiological functions was performed using Y-maze tests, wheel running tests, accelerated rotarod tests, balance beam tests, and forced swimming tests (FSTs), using adult mice after 50 weeks of administering living probiotic bacterium Lactobacillus fermentum strain JDFM216 or a vehicle. Immunomodulatory function was investigated using immune organs, immune cells and immune molecules in the mice, and gut microbiota was also evaluated in their feces. Notably, the L. fermentum JDFM216-treated group showed significantly better performance in the behavior tests (P < 0.05) as well as improved phagocytic activity of macrophages, enhanced sIgA production, and stimulated immune cells (P < 0.05). In aged mice, we observed decreases in species belonging to the Porphyromonadaceae family and the Lactobacillus genus when compared to young mice. While administering the supplementation of L. fermentum JDFM216 to aged mice did not shift the whole gut microbiota, the abundance of Lactobacillus species was significantly increased (P < 0.05). Our findings suggested that L. fermentum JDFM216 also provided beneficial effects on the regulation of immune responses, which has promising implications for functional foods. Taken together, L. fermentum JDFM216 could confer the benefit of improving health with enhanced cognition, physiological behavior, and immunity by modulating the gut microbiota.

scholarly journals Nano-Biomimetic Drug Delivery Vehicles: Potential Approaches for COVID-19 Treatment

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5952
Author(s):  
Bwalya A. Witika ◽  
Pedzisai A. Makoni ◽  
Larry L. Mweetwa ◽  
Pascal V. Ntemi ◽  
Melissa T. R. Chikukwa ◽  
...  
Keyword(s):  
Drug Delivery ◽  
Targeted Delivery ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Charge Composition ◽  
Drug Delivery Vehicles ◽  
Therapeutic Outcomes ◽  
Delivery Vehicles ◽  
The Impact

The current COVID-19 pandemic has tested the resolve of the global community with more than 35 million infections worldwide and numbers increasing with no cure or vaccine available to date. Nanomedicines have an advantage of providing enhanced permeability and retention and have been extensively studied as targeted drug delivery strategies for the treatment of different disease. The role of monocytes, erythrocytes, thrombocytes, and macrophages in diseases, including infectious and inflammatory diseases, cancer, and atherosclerosis, are better understood and have resulted in improved strategies for targeting and in some instances mimicking these cell types to improve therapeutic outcomes. Consequently, these primary cell types can be exploited for the purposes of serving as a “Trojan horse” for targeted delivery to identified organs and sites of inflammation. State of the art and potential utilization of nanocarriers such as nanospheres/nanocapsules, nanocrystals, liposomes, solid lipid nanoparticles/nano-structured lipid carriers, dendrimers, and nanosponges for biomimicry and/or targeted delivery of bioactives to cells are reported herein and their potential use in the treatment of COVID-19 infections discussed. Physicochemical properties, viz., hydrophilicity, particle shape, surface charge, composition, concentration, the use of different target-specific ligands on the surface of carriers, and the impact on carrier efficacy and specificity are also discussed.

scholarly journals Early growth and postprandial appetite regulatory hormone responses

2013 ◽  
Vol 110 (9) ◽  
pp. 1591-1600 ◽  
Author(s):  
Mia-Maria Perälä ◽  
Eero Kajantie ◽  
Liisa M. Valsta ◽  
Jens J. Holst ◽  
Jaana Leiviskä ◽  
...  
Keyword(s):  
Test Meal ◽  
Metabolic Diseases ◽  
Hormone Secretion ◽  
Later Life ◽  
Early Growth ◽  
Birth Cohort Study ◽  
Slow Increase ◽  
Increased Risk ◽  
Hormone Responses ◽  
The Impact

Strong epidemiological evidence suggests that slow prenatal or postnatal growth is associated with an increased risk of CVD and other metabolic diseases. However, little is known whether early growth affects postprandial metabolism and, especially, the appetite regulatory hormone system. Therefore, we investigated the impact of early growth on postprandial appetite regulatory hormone responses to two high-protein and two high-fat content meals. Healthy, 65–75-year-old volunteers from the Helsinki Birth Cohort Study were recruited; twelve with a slow increase in BMI during the first year of life (SGI group) and twelve controls. Subjects ate a test meal (whey meal, casein meal, SFA meal and PUFA meal) once in a random order. Plasma glucose, insulin, TAG, NEFA, ghrelin, peptide tyrosine-tyrosine (PYY), glucose-dependent insulinotropic peptide, glucagon-like peptide-1 and a satiety profile were measured in the fasting state and for 4 h after each test meal. Compared with the controls, the SGI group had about 1·5-fold higher insulin responses after the whey meal (P= 0·037), casein meal (P= 0·023) and PUFA meal (P= 0·002). TAG responses were 34–69 % higher for the SGI group, but only the PUFA-meal responses differed significantly between the groups. The PYY response of the SGI group was 44 % higher after the whey meal (P= 0·046) and 115 % higher after the casein meal (P= 0·025) compared with the controls. No other statistically significant differences were seen between the groups. In conclusion, early growth may have a role in programming appetite regulatory hormone secretion in later life. Slow early growth is also associated with higher postprandial insulin and TAG responses but not with incretin levels.

scholarly journals Ghrelin and Des-Acyl Ghrelin Promote Differentiation and Fusion of C2C12 Skeletal Muscle Cells

2007 ◽  
Vol 18 (3) ◽  
pp. 986-994 ◽  
Author(s):  
Nicoletta Filigheddu ◽  
Viola F. Gnocchi ◽  
Marco Coscia ◽  
Miriam Cappelli ◽  
Paolo E. Porporato ◽  
...  
Keyword(s):  
Growth Hormone ◽  
Ectopic Expression ◽  
Cell Types ◽  
C2c12 Cells ◽  
Growth Hormone Secretagogue Receptor ◽  
Endocrine Activity ◽  
Growth Hormone Secretagogue ◽  
Inhibition Of Proliferation ◽  
Acyl Ghrelin

Ghrelin is an acylated peptidyl gastric hormone acting on the pituitary and hypothalamus to stimulate appetite, adiposity, and growth hormone release, through activation of growth hormone secretagogue receptor (GHSR)-1a receptor. Moreover, ghrelin features several activities such as inhibition of apoptosis, regulation of differentiation, and stimulation or inhibition of proliferation of several cell types. Ghrelin acylation is absolutely required for both GHSR-1a binding and its central endocrine activities. However, the unacylated ghrelin form, des-acyl ghrelin, which does not bind GHSR-1a and is devoid of any endocrine activity, is far more abundant than ghrelin in plasma, and it shares with ghrelin some of its cellular activities. Inhere we show that both ghrelin and des-acyl ghrelin stimulate proliferating C2C12 skeletal myoblasts to differentiate and to fuse into multinucleated myotubes in vitro through activation of p38. Consistently, both ghrelin and des-acyl ghrelin inhibit C2C12 proliferation in growth medium. Moreover, the ectopic expression of ghrelin in C2C12 enhances differentiation and fusion of these myoblasts in differentiation medium. Finally, we show that C2C12 cells do not express GHSR-1a, but they do contain a common high-affinity binding site recognized by both acylated and des-acylated ghrelin, suggesting that the described activities on C2C12 are likely mediated by this novel, yet unidentified receptor for both ghrelin forms.

scholarly journals OP13 Mucosal organoids capture Innate Lymphoid Cells (ILC) tissue-specific development and reveal that Inflammatory Bowel Disease-associated ILC modulate intestinal remodelling

2021 ◽  
Vol 15 (Supplement_1) ◽  
pp. S013-S014
Author(s):  
G M Jowett ◽  
E Read ◽  
M D Norman ◽  
P A Arevalo ◽  
M Vilà González ◽  
...  
Keyword(s):  
Inflammatory Bowel Disease ◽  
Bowel Disease ◽  
Inflammatory Diseases ◽  
Cell Types ◽  
Innate Lymphoid Cells ◽  
Lymphoid Cells ◽  
Tissue Specific ◽  
Final Maturation ◽  
Inflammatory Bowel ◽  
The Impact

Abstract Background Innate Lymphoid Cells (ILC) develop from Common Lymphoid Precursors in the bone marrow, and ILC precursors (ILCP) migrate to mucosa where they mature, promote homeostasis, and provide a potent, antigen-non-specific sources of cytokines. Deciphering what local stimuli drive the final stages of ILCP maturation in these tissues remains a pressing question, as ILC frequencies can become dysregulated during chronic infection and inflammatory diseases. For example, Type-1 innate lymphoid cells (ILC1) are enriched in the mucosa of patients with active inflammatory bowel disease (IBD) and the impact of this accumulation remains elusive. Methods Here, we develop and use co-cultures of both murine and human iPSC-derived gut and lung organoids with ILCP and with mature ILC isolated from IBD patients’ intestinal biopsies. Results Harnessing these versatile models, we demonstrate that epithelial cells provide a complex niche capable of supporting the final maturation of all helper-like ILC1, ILC2, and ILC3. Notably, organoid identity was sufficient to robustly recapitulate tissue-specific ILC imprints and frequencies, even in the absence of microbial stimuli, other cell types, or cytokine supplementation. In addition, we show that that ILC1 drive expansion of the epithelial stem cell crypt through p38γ phosphorylation, driving a potentially pathological proliferative feedback loop between β-catenin and Cd44v6. We harnessed this model to elucidate that this phenotype was unexpectedly regulated by ILC1-derived TGFβ1. We further show that human gut ILC1 also secrete TGFβ1, and drive CD44v6 expression in both HIO epithelium and mesenchyme. As TGFβ1 is a master regulator of fibrosis, the leading indicator for surgery in IBD, we next characterised the ability of ILC1 to regulate matrix remodelling using a functionalized, synthetic hydrogel system. We show that ILC1 drive both matrix stiffening and degradation, which we posit occurs through a balance of MMP9 degradation and TGFβ1-induced fibronectin deposition. Conclusion Taken together, our work provides unprecedented insight into in situ ILC maturation, which we show to be driven by epithelial signals, and into ILC function. We also report that intestinal ILC1 modulate epithelial and matrix remodelling, which may drive either wound healing in homeostasis, but may tip toward pathology when enriched in IBD. Moreover, our work introduces a modular organoid platform, which provides exquisite control over both environmental stimuli and host genetics, making it a powerful tool for dissecting the interactions between complex mucosal tissues and rare cell subtypes in development and disease.

scholarly journals Inflammation and Insulin Resistance as Risk Factors and Potential Therapeutic Targets for Alzheimer’s Disease

2021 ◽  
Vol 15 ◽  
Author(s):  
Angeles Vinuesa ◽  
Carlos Pomilio ◽  
Amal Gregosa ◽  
Melisa Bentivegna ◽  
Jessica Presa ◽  
...  
Keyword(s):  
Risk Factors ◽  
Alzheimer’S Disease ◽  
Insulin Resistance ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Brain Aging ◽  
Therapeutic Targets ◽  
Low Grade ◽  
Increased Risk ◽  
The Impact

Overnutrition and modern diets containing high proportions of saturated fat are among the major factors contributing to a low-grade state of inflammation, hyperglycemia and dyslipidemia. In the last decades, the global rise of type 2 diabetes and obesity prevalence has elicited a great interest in understanding how changes in metabolic function lead to an increased risk for premature brain aging and the development of neurodegenerative disorders such as Alzheimer’s disease (AD). Cognitive impairment and decreased neurogenic capacity could be a consequence of metabolic disturbances. In these scenarios, the interplay between inflammation and insulin resistance could represent a potential therapeutic target to prevent or ameliorate neurodegeneration and cognitive impairment. The present review aims to provide an update on the impact of metabolic stress pathways on AD with a focus on inflammation and insulin resistance as risk factors and therapeutic targets.

scholarly journals Dooming Phagocyte Responses: Inflammatory Effects of Endogenous Oxidized Phospholipids

2021 ◽  
Vol 12 ◽  
Author(s):  
Marco Di Gioia ◽  
Ivan Zanoni
Keyword(s):  
Immune Cells ◽  
Molecular Mechanisms ◽  
Inflammatory Responses ◽  
Inflammatory Diseases ◽  
Biological Activities ◽  
Oxidized Lipids ◽  
Oxidized Phospholipids ◽  
Clinical Tools ◽  
Stress Mediators ◽  
The Impact

Endogenous oxidized phospholipids are produced during tissue stress and are responsible for sustaining inflammatory responses in immune as well as non-immune cells. Their local and systemic production and accumulation is associated with the etiology and progression of several inflammatory diseases, but the molecular mechanisms that underlie the biological activities of these oxidized phospholipids remain elusive. Increasing evidence highlights the ability of these stress mediators to modulate cellular metabolism and pro-inflammatory signaling in phagocytes, such as macrophages and dendritic cells, and to alter the activation and polarization of these cells. Because these immune cells serve a key role in maintaining tissue homeostasis and organ function, understanding how endogenous oxidized lipids reshape phagocyte biology and function is vital for designing clinical tools and interventions for preventing, slowing down, or resolving chronic inflammatory disorders that are driven by phagocyte dysfunction. Here, we discuss the metabolic and signaling processes elicited by endogenous oxidized lipids and outline new hypotheses and models to elucidate the impact of these lipids on phagocytes and inflammation.

scholarly journals A Brazilian Cohort of Patients With Immuno-Mediated Chronic Inflammatory Diseases Infected by SARS-CoV-2 (ReumaCoV-Brasil Registry): Protocol for a Prospective, Observational Study

10.2196/24357 ◽  
2020 ◽  
Vol 9 (12) ◽  
pp. e24357
Author(s):  
Claudia Marques ◽  
Adriana Maria Kakehasi ◽  
Ana Paula Monteiro Gomides ◽  
Eduardo Dos Santos Paiva ◽  
Edgard Torres dos Reis Neto ◽  
...  
Keyword(s):  
Clinical Laboratory ◽  
Inflammatory Diseases ◽  
Progression Rate ◽  
Immune Mediated ◽  
Increased Risk ◽  
Observational Cohort ◽  
And Function ◽  
The Impact ◽  
Brazilian Cohort

Background Patients with immune-mediated rheumatic diseases (IMRD) are at increased risk of infections, including significant morbidity and high mortality. Considering the potential for unfavorable outcomes of SARS-CoV-2 infection in patients with IMRD, several questions were raised regarding the impact of COVID-19 at the start of the pandemic. Objective This paper presents the protocol of a study that aims to prospectively evaluate patients with IMRD and a confirmed COVID-19 diagnosis (using criteria provided by the Brazilian Ministry of Health). Methods The study comprised a prospective, observational cohort (patients with IMRD and COVID-19) and a comparison group (patients with only IMRD), with a follow-up time of 6 months to evaluate differences in health outcomes. The primary outcomes will be changes in IMRD disease activity after SARS-CoV-2 infection at 4 time points: (1) at baseline, (2) within 4-6 weeks after infection, (3) at 3 months after the second assessment (±15 days), and (4) at 6 months (±15 days). The secondary outcomes will be the progression rate to moderate or severe forms of COVID-19, need for intensive care unit admission and mechanical ventilation, death, and therapeutic changes related to IMRD. Two outcomes—pulmonary and thromboembolic events in patients with both IMRD and SARS-CoV-2 infection—are of particular interest and will be monitored with close attention (clinical, laboratory, and function tests as well as imaging). Results Recruitment opened in May 2020, with 1300 participants recruited from 43 sites as of November 2020. Patient recruitment will conclude by the end of December 2020, with follow-up occurring until April 2021. Data analysis is scheduled to start after all inclusion data have been collected, with an aim to publish a peer-reviewed paper in December 2020. Conclusions We believe this study will provide clinically relevant data on the general impact of COVID-19 on patients with IMRD. Trial Registration Brazilian Registry of Clinical Trials RBR-33YTQC; http://www.ensaiosclinicos.gov.br/rg/RBR-33ytqc/ International Registered Report Identifier (IRRID) DERR1-10.2196/24357

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