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Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools

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A special issue of Biology (ISSN 2079-7737). This special issue belongs to the section "Medical Biology".

Deadline for manuscript submissions: closed (30 March 2023) | Viewed by 34439

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Special Issue Editors

Dr. Vera Francisco

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Guest Editor

SERGAS, Xerencia Xestión Integrada de Santiago, Santiago University Clinical Hospital, 15706 Santiago de Compostela, A Coruña, Spain
Interests: inflammation; obesity; translational medicine; natural products

Dr. Oreste Gualillo

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Guest Editor

Servizo Galego de Saude and Institute of Biomedical Research (SERGAS-IDIS), The NEIRID LAB, Neuroendocrine Interactions in Rheumatology and Inflammatory Diseases, Santiago University Clinical Hospital, 15706 Santiago de Compostela, A Coruña, Spain
Interests: leptin; adipokines; inflammation; arthritis; cartilage pathophysiology; immunometabolism; natural drugs
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Dr. Jan Van den Bossche

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Department of Molecular Cell Biology and Immunology, Amsterdam UMC, 1081 HZ Amsterdam, The Netherlands
Interests: immunometabolism; innate immunity; macrophage heterogeneity and plasticity; immunometabolites
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Metabolic syndrome (MetS) represents one of the major public health challenges worldwide. Defined as a cluster of medical conditions that significantly increase the risk of developing cardiovascular diseases and Type 2 Diabetes, MetS also associates with diverse comorbidities, like nonalcoholic fatty liver disease (NAFLD), different cancer, chronic kidney disease, polycystic ovarian syndrome, rheumatic diseases, obstructive sleep apnea, and depressive disorder.

Abdominal adiposity and related chronic low-grade inflammation are driving forces in the MetS pathophysiology. Obese individuals are characterized by altered circulating cytokine profiles (e.g., increased levels of C-reactive protein, pro-inflammatory cytokines, and adipokines), immune cell infiltration into tissues (macrophages, neutrophils, dendritic cells, lymphocytes, etc.), and activation of inflammatory pathways within tissues parenchyma, hence propagating the cycle of metabolic inflammation. Along with peripheral inflammation, the involvement of the central nervous system (CNS) immune cells in metabolic dysfunction has also been revealed.

Conversely, activation of these distinct immune cells is regulated by systemic as well as intracellular metabolic changes. Immunometabolism research comprises this complex interplay of metabolism and immunity at the systemic and cellular level. This rapidly growing field had taught us how metabolic processes not only generate energy and biosynthetic precursors, but also directly control immunity, inflammation, and disease outcome.

Understanding the intricate links between metabolism and inflammation is thus crucial to precisely identify early specific components determining disease pathophysiology and determine molecular and cellular processes whose modulation can lead to effective therapeutic approaches.

This Special Issue welcomes basic and translational original and review articles focused on inflammatory mechanisms in metabolic syndrome and mechanisms by which the metabolism controls immune cell activation. Potential topics include, but are not limited to, basic molecular and cellular inflammatory mechanisms, inflammatory markers, and novel agents and therapeutics targeting inflammation and (immune)metabolism in metabolic syndrome and associated comorbidities.

Dr. Vera Francisco
Dr. Oreste Gualillo
Dr. Jan Van den Bossche
Guest Editors

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Keywords

inflammation
metabolism
immunometabolism
obesity
cardiovascular diseases
diabetes
metabolic syndrome comorbidities
biomarkers

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Published Papers (8 papers)

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Research

Jump to: Review

13 pages, 2027 KiB

Open AccessArticle

Farnesol-Loaded Nanoliposomes Inhibit Inflammatory Gene Expression in Primary Human Skeletal Myoblasts

by Eva Mückter, Maria Lozoya, Aline Müller, Volkmar Weissig and Mahtab Nourbakhsh

Biology 2022, 11(5), 701; https://doi.org/10.3390/biology11050701 - 2 May 2022

Cited by 3 | Viewed by 2284

Abstract

There is a substantial unmet need for the treatment of skeletal muscle mass loss that is associated with aging and obesity-related increases in FFA. Unsaturated FFAs stimulate the inflammatory gene expression in human skeletal myoblasts (SkMs). Farnesol is a hydrophobic acyclic sesquiterpene alcohol with potential anti-inflammatory effects. Here, we created farnesol-loaded small unilamellar (SUVs) or multilamellar lipid-based vesicles (MLVs), and investigated their effects on inflammatory gene expression in primary human skeletal myoblasts. The attachment of SUVs or MLVs to SkMs was tracked using BODIPY, a fluorescent lipid dye. The data showed that farnesol-loaded SUVs reduced FFA-induced IL6 and LIF expression by 77% and 70% in SkMs, respectively. Farnesol-loaded MLVs were less potent in inhibiting FFA-induced IL6 and LIF expression. In all experiments, equal concentrations of free farnesol did not exert significant effects on SkMs. This report suggests that farnesol, if efficiently directed into myoblasts through liposomes, may curb FFA-induced inflammation in human skeletal muscle. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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12 pages, 1286 KiB

Open AccessArticle

Angiogenin Levels and Their Association with Cardiometabolic Indices Following Vitamin D Status Correction in Saudi Adults

by Ghadeer M. Aldawsari, Shaun Sabico, Abir A. Alamro, Amal Alenad, Kaiser Wani, Abdullah M. Alnaami, Malak N. K. Khattak, Mohammad S. Masoud, Nasser M. Al-Daghri and Majed S. Alokail

Biology 2022, 11(2), 286; https://doi.org/10.3390/biology11020286 - 11 Feb 2022

Cited by 2 | Viewed by 1987

Abstract

Angiogenin (ANG), a multifunctional protein known to induce blood vessel formation, is a potential biomarker for cardiovascular diseases; however, whether it is affected by vitamin D supplementation is not known. This interventional study in vitamin D-deficient Saudi adults was designed to investigate it. A total of 100 vitamin D-deficient Saudi adults aged 30–50 years were randomly selected to undergo 6-month vitamin D supplementation. Circulating levels of fasting glucose, lipids, vitamin D, apolipoproteins (AI, AII, B, CI, CII, CIII, E, and H), and ANG were measured using commercially available assays at baseline and after six months. Overall, vitamin D levels increased significantly post intervention. With this, levels of apo-CIII and apo-E significantly increased (p-values of 0.001 and 0.009, respectively) with a significant parallel decrease in apo-B (p = 0.003). ANG levels were significantly positively associated with most apolipoproteins and inversely correlated with HDL-cholesterol. Post intervention, the changes in ANG levels were positively correlated with apo-E (r = 0.32; p < 0.01 in all subjects and r = 0.40; p < 0.05 in males). Vitamin D supplementation may modestly affect ANG levels. The association observed between ANG and apo-E is worthy of further investigation since both biomarkers have been linked to neurodegenerative disorders. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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20 pages, 5728 KiB

Open AccessArticle

Replication of Integrative Data Analysis for Adipose Tissue Dysfunction, Low-Grade Inflammation, Postprandial Responses and OMICs Signatures in Symptom-Free Adults

by Esther C. Gallegos-Cabriales, Ernesto Rodriguez-Ayala, Hugo A. Laviada-Molina, Edna J. Nava-Gonzalez, Rocío A. Salinas-Osornio, Lorena Orozco, Irene Leal-Berumen, Juan Carlos Castillo-Pineda, Laura Gonzalez-Lopez, Claudia Escudero-Lourdes, Judith Cornejo-Barrera, Fabiola Escalante-Araiza, Eira E. Huerta-Avila, Fatima A. Buenfil-Rello, Vanessa-Giselle Peschard, Eliud Silva, Rosa A. Veloz-Garza, Angelica Martinez-Hernandez, Francisco M. Barajas-Olmos, Fernanda Molina-Segui, Lucia Gonzalez-Ramirez, Ruy D. Arjona-Villicaña, Victor M. Hernandez-Escalante, Janeth F. Gaytan-Saucedo, Zoila Vaquera, Monica Acebo-Martinez, Areli Murillo-Ramirez, Sara P. Diaz-Tena, Benigno Figueroa-Nuñez, Melesio E. Valencia-Rendon, Rafael Garzon-Zamora, Juan Manuel Viveros-Paredes, Salvador B. Valdovinos-Chavez, Anthony G Comuzzie, Karin Haack, Ashley A. Thorsell, Xianlin Han, Shelley A. Cole and Raul A. Bastarrachea Show full author list Hide full author list

Biology 2021, 10(12), 1342; https://doi.org/10.3390/biology10121342 - 16 Dec 2021

Cited by 1 | Viewed by 5790

Abstract

We previously reported preliminary characterization of adipose tissue (AT) dysfunction through the adiponectin/leptin ratio (ALR) and fasting/postprandial (F/P) gene expression in subcutaneous (SQ) adipose tissue (AT) biopsies obtained from participants in the GEMM study, a precision medicine research project. Here we present integrative data replication of previous findings from an increased number of GEMM symptom-free (SF) adults (N = 124) to improve characterization of early biomarkers for cardiovascular (CV)/immunometabolic risk in SF adults with AT dysfunction. We achieved this goal by taking advantage of the rich set of GEMM F/P 5 h time course data and three tissue samples collected at the same time and frequency on each adult participant (F/P blood, biopsies of SQAT and skeletal muscle (SKM)). We classified them with the presence/absence of AT dysfunction: low (<1) or high (>1) ALR. We also examined the presence of metabolically healthy (MH)/unhealthy (MUH) individuals through low-grade chronic subclinical inflammation (high sensitivity C-reactive protein (hsCRP)), whole body insulin sensitivity (Matsuda Index) and Metabolic Syndrome criteria in people with/without AT dysfunction. Molecular data directly measured from three tissues in a subset of participants allowed fine-scale multi-OMIC profiling of individual postprandial responses (RNA-seq in SKM and SQAT, miRNA from plasma exosomes and shotgun lipidomics in blood). Dynamic postprandial immunometabolic molecular endophenotypes were obtained to move towards a personalized, patient-defined medicine. This study offers an example of integrative translational research, which applies bench-to-bedside research to clinical medicine. Our F/P study design has the potential to characterize CV/immunometabolic early risk detection in support of precision medicine and discovery in SF individuals. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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14 pages, 1779 KiB

Open AccessArticle

Free Fatty Acid Species Differentially Modulate the Inflammatory Gene Response in Primary Human Skeletal Myoblasts

by Melanie Rauen, Dandan Hao, Aline Müller, Eva Mückter, Leo Cornelius Bollheimer and Mahtab Nourbakhsh

Biology 2021, 10(12), 1318; https://doi.org/10.3390/biology10121318 - 12 Dec 2021

Cited by 6 | Viewed by 3021

Abstract

Age-related loss of skeletal muscle is associated with obesity and inflammation. In animal models, intramuscular fat deposits compromise muscle integrity; however, the relevant fat components that mediate muscular inflammation are not known. Previously, we hypothesized that free fatty acids (FFAs) may directly induce inflammatory gene expression in skeletal muscle cells of obese rats. Here, we examined this hypothesis in primary human skeletal myoblasts (SkMs) using multiplex expression analysis of 39 inflammatory proteins in response to different FFA species. Multiplex mRNA quantification confirmed that the IL6, IL1RA, IL4, LIF, CXCL8, CXCL1, CXCL12 and CCL2 genes were differentially regulated by saturated and unsaturated C16 or C18 FFAs. Fluorescence staining revealed that only saturated C16 and C18 strongly interfere with myoblast replication independent of desmin expression, mitochondrial abundance and oxidative activity. Furthermore, we addressed the possible implications of 71 human receptor tyrosine kinases (RTKs) in FFA-mediated effects. Phosphorylated EphB6 and TNK2 were associated with impaired myoblast replication by saturated C16 and C18 FFAs. Our data suggest that abundant FFA species in human skeletal muscle tissue may play a decisive role in the progression of sarcopenic obesity by affecting inflammatory signals or myoblast replication. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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10 pages, 764 KiB

Open AccessArticle

Tristetraprolin, Inflammation, and Metabolic Syndrome in Arab Adults: A Case Control Study

by Nasser M. Al-Daghri, Albatul Y.A. Al-Shuwaie, Amani Alghamdi, Osama E. Amer, Malak N.K. Khattak, Mohammed G.A. Ansari, Abdullah M. Alnaami and Shaun Sabico

Biology 2021, 10(6), 550; https://doi.org/10.3390/biology10060550 - 18 Jun 2021

Cited by 4 | Viewed by 2638

Abstract

Tristetraprolin (TTP) is an mRNA binding protein suggested to have a substantial role in regulating the mRNA expression of numerous inflammatory factors, but data on TTP and its association with metabolic syndrome (MetS), a chronic low-grade inflammatory disorder, are scarce. We hypothesize that TTP may modulate MetS and its components. A total of 200 Saudi adults (aged 38.6 ± 8.3 years) were included in this cross-sectional study. Anthropometrics data were collected and fasting blood glucose taken for the assessment of glycemic, lipids and inflammatory markers using commercially available assays. The National Cholesterol Education Program Adult Treatment Panel (NCEP ATP III) criteria were used to define MetS. Results showed significantly higher levels of TTP in the MetS group than in controls [288.1 pg/mL vs. 150.9 pg/mL, p < 0.001]. Circulating TTP was significantly associated with tumor necrosis factor alpha [TNF-α, R = 0.30, p < 0.05], interleukin 1β [IL-1β, R = 0.41, p < 0.01] and C-reactive protein [CRP, R = 0.36, p < 0.01], adiponectin [R = 0.36, p < 0.05], insulin [R = 0.37, p < 0.05], and insulin resistance [HOMA-IR, R = 0.40, p < 0.05]. Receiver operating characteristics (ROC) suggest a potential use of TTP as diagnostic biomarker for MetS [AUC = 0.819, p < 0.001]. The findings suggest that TTP is associated with inflammation and glycemia, which may influence MetS. TTP is a promising diagnostic biomarker for MetS which can be confirmed in larger cohorts. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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Review

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19 pages, 1334 KiB

Open AccessReview

by Tamás Ilyés, Ciprian N. Silaghi and Alexandra M. Crăciun

Biology 2022, 11(11), 1556; https://doi.org/10.3390/biology11111556 - 24 Oct 2022

Cited by 20 | Viewed by 5377

Abstract

Obesity-related illnesses are one of the leading causes of death worldwide. Metabolic syndrome has been associated with numerous health issues. Short-chain fatty acids (SCFAs) have been shown to have multiple effects throughout the body, both directly as well as through specific G protein-coupled receptors. The main SCFAs produced by the gut microbiota are acetate, propionate, and butyrate, which are absorbed in varying degrees from the large intestine, with some acting mainly locally and others systemically. Diet has the potential to influence the gut microbial composition, as well as the type and amount of SCFAs produced. High fiber-containing foods and supplements increase the production of SCFAs and SCFA-producing bacteria in the gut and have been shown to have bodyweight-lowering effects. Dietary supplements, which increase SCFA production, could open the way for novel approaches to weight loss interventions. The aim of this review is to analyze the variations of fecal and blood SCFAs in obesity and metabolic syndrome through a systematic search and analysis of existing literature. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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26 pages, 1248 KiB

Open AccessReview

Adipokines in Non-Alcoholic Fatty Liver Disease: Are We on the Road toward New Biomarkers and Therapeutic Targets?

by Vera Francisco, Maria Jesus Sanz, José T. Real, Patrice Marques, Maurizio Capuozzo, Djedjiga Ait Eldjoudi and Oreste Gualillo

Biology 2022, 11(8), 1237; https://doi.org/10.3390/biology11081237 - 19 Aug 2022

Cited by 44 | Viewed by 5071

Abstract

Non-alcoholic fatty liver disease (NAFLD) has become the major cause of chronic hepatic illness and the leading indication for liver transplantation in the future decades. NAFLD is also commonly associated with other high-incident non-communicable diseases, such as cardiovascular complications, type 2 diabetes, and chronic kidney disease. Aggravating the socio-economic impact of this complex pathology, routinely feasible diagnostic methodologies and effective drugs for NAFLD management are unavailable. The pathophysiology of NAFLD, recently defined as metabolic associated fatty liver disease (MAFLD), is correlated with abnormal adipose tissue–liver axis communication because obesity-associated white adipose tissue (WAT) inflammation and metabolic dysfunction prompt hepatic insulin resistance (IR), lipid accumulation (steatosis), non-alcoholic steatohepatitis (NASH), and fibrosis. Accumulating evidence links adipokines, cytokine-like hormones secreted by adipose tissue that have immunometabolic activity, with NAFLD pathogenesis and progression; however, much uncertainty still exists. Here, the current knowledge on the roles of leptin, adiponectin, ghrelin, resistin, retinol-binding protein 4 (RBP4), visfatin, chemerin, and adipocyte fatty-acid-binding protein (AFABP) in NAFLD, taken from preclinical to clinical studies, is overviewed. The effect of therapeutic interventions on adipokines’ circulating levels are also covered. Finally, future directions to address the potential of adipokines as therapeutic targets and disease biomarkers for NAFLD are discussed. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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17 pages, 1552 KiB

Open AccessReview

Immune-Mediated Diseases from the Point of View of Psychoneuroimmunoendocrinology

by Miguel A. Ortega, Cielo García-Montero, Oscar Fraile-Martinez, Miguel Angel Alvarez-Mon, Ana Maria Gómez-Lahoz, Guillermo Lahera, Jorge Monserrat, Roberto Rodriguez-Jimenez, Javier Quintero and Melchor Álvarez-Mon

Biology 2022, 11(7), 973; https://doi.org/10.3390/biology11070973 - 28 Jun 2022

Cited by 14 | Viewed by 6114

Abstract

Immune-mediated inflammatory diseases (IMIDs) represent a large group of diseases (Crohn’s, ulcerative colitis, psoriasis, lupus, and rheumatoid arthritis) evidenced by systemic inflammation and multiorgan involvement. IMIDs result in a reduced quality of life and an economic burden for individuals, health care systems, and countries. In this brief descriptive review, we will focus on some of the common biological pathways of these diseases from the point of view of psychoneuroimmunoendocrinology (PNIE). PNIE consists of four medical disciplines (psychology, nervous system, immune system, and endocrine system), which are key drivers behind the health–disease concept that a human being functions as a unit. We examine these drivers and emphasize the need for integrative treatments that addresses the disease from a psychosomatic point of view. Full article

(This article belongs to the Special Issue Immunometabolic Crosstalk in Inflammation and Metabolic Syndrome: New Biomarkers and Therapeutic Tools)

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