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Understanding Metabolic Cross-Talk in Health and Disease

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Endocrinology and Metabolism".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 7794

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Special Issue Editor

Dr. Marcelina Parrizas

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Guest Editor

Laboratori de Diabetis i Obesitat, CIBERDEM, 08036 Barcelona, Spain
Interests: metabolic disorders (particularly type 2 diabetes and obesity); epigenetics; exosomes; microRNAs and tissue crosstalk in the regulation of metabolism
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Maintenance of metabolic homeostasis requires complex crosstalk not only among the different organs that conform the body but also between them and the myriad of microorganisms associated with it. A variety of mediators including nutrients, hormones, and extracellular vesicles released by all cell types and the intestinal microbiome, elicit cellular responses by acting as signaling mediators to coordinate the adaptation of the organism as a whole to the diverse physiological and nutritional states it encounters. Environmental influences may disturb tissue crosstalk, leading to decompensations in fuel use that ultimately result in insulin resistance, obesity, and overt disease.

This Special Issue aims to highlight the latest research exploring how metabolic crosstalk in the broad sense, including the different organs and cell types, the microbiome, and the ingested nutrients, can be disturbed in pathological conditions such as obesity, liver cirrhosis, or cancer, but also with physiological challenges, including exercise or intermittent fasting. The topics that we intend to cover include but are not limited to the following:

Regulation of metabolic crosstalk by diet and exercise
Extracellular vesicles and their cargo in the regulation of metabolism
Crosstalk between the gut microbiome and the host
Tissue crosstalk in metabolic diseases and cancer.

Dr. Marcelina Parrizas
Guest Editor

Manuscript Submission Information

Manuscripts should be submitted online at www.mdpi.com by registering and logging in to this website. Once you are registered, click here to go to the submission form. Manuscripts can be submitted until the deadline. All submissions that pass pre-check are peer-reviewed. Accepted papers will be published continuously in the journal (as soon as accepted) and will be listed together on the special issue website. Research articles, review articles as well as short communications are invited. For planned papers, a title and short abstract (about 100 words) can be sent to the Editorial Office for announcement on this website.

Submitted manuscripts should not have been published previously, nor be under consideration for publication elsewhere (except conference proceedings papers). All manuscripts are thoroughly refereed through a single-blind peer-review process. A guide for authors and other relevant information for submission of manuscripts is available on the Instructions for Authors page. International Journal of Molecular Sciences is an international peer-reviewed open access semimonthly journal published by MDPI.

Please visit the Instructions for Authors page before submitting a manuscript. There is an Article Processing Charge (APC) for publication in this open access journal. For details about the APC please see here. Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

crosstalk
metabolism
obesity
diabetes
cancer
exosomes
microbiome
miRNA
hormones

Published Papers (5 papers)

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Research

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18 pages, 9470 KiB

Open AccessArticle

Semaglutide Modulates Extracellular Matrix Production of LX-2 Cells via Exosomes and Improves Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD)

by Maria Principia Scavo, Giuseppe Lisco, Nicoletta Depalo, Federica Rizzi, Sara Volpe, Valentina Arrè, Livianna Carrieri, Maria Notarnicola, Valentina De Nunzio, Maria Lucia Curri, Giovanni De Pergola, Giuseppina Piazzolla and Gianluigi Giannelli

Int. J. Mol. Sci. 2024, 25(3), 1493; https://doi.org/10.3390/ijms25031493 - 25 Jan 2024

Cited by 1 | Viewed by 1376

Abstract

Metabolic dysfunction-associated steatotic liver disease (MASLD) is closely related to some metabolic disorders, such as central obesity and type 2 diabetes (T2D). Glucagon-like peptide 1 receptor agonists (GLP-1RAs), such as semaglutide, may have therapeutic roles in MASLD associated with T2D. This study aims to investigate the molecular mechanisms underlying the effectiveness of semaglutide on MASLD in terms of progression from liver steatosis to fibrosis. We characterized exosomes from ten patients with type 2 diabetes (T2D) before (T0) and after 12 months (T12) of treatment with once-weekly subcutaneous semaglutide. Six of ten patients were considered responders to therapy (R) based on MASLD severity downgrading by at least one class according to a validated ultrasonographic (US) score. Normal hepatocytes (HEPA-RG) and stellate (LX-2) cells were challenged with exosomes from R and NR patients, isolated before and after 12 months of therapy. Exosomes from both R and NR patients isolated at T0 significantly affected LX-2 viability. After 12 months of treatment, only those isolated from R patients restored cell viability, whereas those from NR patients did not. No effects were observed on HEPA-RG cells. Exosomes at T12 from R but not from NR patients significantly decreased the production of α-SMA, a marker of LX-2 activation, a liver stellate cell model, and ph-SMAD2 and CTGF, involved in fibrosis processes. TGF-β1 was not modulated by the exosomes of R and NR patients. As a downstream effect, Vimentin, Collagen 1A1, and Fibronectin extracellular matrix components were also downregulated, as measured by droplets digital PCR. In conclusion, these results shed light on the potential effectiveness of semaglutide in improving liver fibrosis in MASLD. Full article

(This article belongs to the Special Issue Understanding Metabolic Cross-Talk in Health and Disease)

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18 pages, 2045 KiB

Open AccessArticle

Tissue and Circulating MicroRNAs 378 and 142 as Biomarkers of Obesity and Its Treatment Response

by Georgy A. Matveev, Natalya V. Khromova, German G. Zasypkin, Yulia A. Kononova, Elena Yu. Vasilyeva, Alina Yu. Babenko and Evgeny V. Shlyakhto

Int. J. Mol. Sci. 2023, 24(17), 13426; https://doi.org/10.3390/ijms241713426 - 30 Aug 2023

Cited by 1 | Viewed by 741

Abstract

Promising approaches to the treatment of obesity include increasing energy expenditure and slowing down fibrogenesis of adipose tissue. The neurotransmitter reuptake inhibitor sibutramine affects appetite and activates lipolysis in a catecholaminergic way. MicroRNAs (miRs) are considered as biomarkers of molecular genetic mechanisms underlying various processes. The profile of a number of miRs is altered in obesity, both in the circulation and in adipose tissue. The aim of this study was to assess the expression levels of miRs (hsa-miR-378a-3p, hsa-miR-142-3p) by real-time polymerase chain reaction in subcutaneous adipose tissue (SAT) and in plasma in patients with different degrees and duration of obesity and during sibutramine therapy. This study included 51 obese patients and 10 healthy subjects with normal weight who formed a control group. The study found that, before treatment, obese patients had no significant difference in the expression level of miR-378 in SAT and plasma compared to the control group, while the expression of miR-142 was significantly decreased in SAT and increased in plasma. A significant elevation in miR-378 expression level was noted in patients with first-degree obesity and duration of less than 10 years, and the decline in miR-142 increased with the duration of obesity. These data indicate a maximal increase in the expression of the adipogenesis inducer miR-378 in the early stages of obesity, a progressive decrease in the expression of the fibrogenesis inhibitor miR-142 in SAT with growth of duration of obesity and the likely presence of antifibrogenic effects of sibutramine realized through miR-142 activation. Full article

(This article belongs to the Special Issue Understanding Metabolic Cross-Talk in Health and Disease)

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12 pages, 581 KiB

Open AccessArticle

Investigation of the Changes in Concentrations of Vitamin D-Binding Protein and Lactoferin in Plasma and Peritoneal Fluid of Patients with Endometriosis

by Barbara Lisowska-Myjak, Ewa Skarżyńska, Monika Wróbel, Grzegorz Mańka, Mariusz Kiecka, Michał Lipa, Damian Warzecha, Robert Spaczyński, Piotr Piekarski, Beata Banaszewska, Artur Jakimiuk, Tadeusz Issat, Wojciech Rokita, Jakub Młodawski, Maria Szubert, Piotr Sieroszewski, Grzegorz Raba, Kamil Szczupak, Tomasz Kluz, Marek Kluza, Mirosław Wielgoś and Piotr Laudański Show full author list Hide full author list

Int. J. Mol. Sci. 2023, 24(9), 7828; https://doi.org/10.3390/ijms24097828 - 25 Apr 2023

Cited by 5 | Viewed by 1329

Abstract

An evaluation of the association between the concentrations of vitamin D-binding protein and lactoferrin in the plasma and peritoneal fluid may facilitate the elucidation of molecular mechanisms in endometriosis. Vitamin D-binding protein and lactoferrin concentrations were measured by ELISA in plasma and peritoneal fluid samples from 95 women with suspected endometriosis as classified by laparoscopy into groups with (n = 59) and without endometriosis (n = 36). There were no differences (p > 0.05) in the plasma and peritoneal fluid concentrations of vitamin D-binding protein and lactoferrin between women with and without endometriosis. In women with endometriosis, there was a significant correlation between plasma and peritoneal fluid vitamin D-binding protein concentrations (r = 0.821; p = 0.000), but there was no correlation between lactoferrin concentrations in those compartments (r = 0.049; p > 0.05). Furthermore, in endometriosis, lactoferrin was found to correlate poorly with vitamin D-binding protein (r= −0.236; p > 0.05) in plasma, while in the peritoneal fluid, the correlation between those proteins was significant (r = 0.399; p = 0.002). The characteristic properties of vitamin D-binding protein and lactoferrin and the associations between their plasma and peritoneal fluid concentrations found in women with endometriosis may provide a novel panel of markers to identify high-risk patients in need of further diagnostic measures. Full article

(This article belongs to the Special Issue Understanding Metabolic Cross-Talk in Health and Disease)

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11 pages, 4382 KiB

Open AccessArticle

Effect of Genetic Factors, Age and Sex on Levels of Circulating Extracellular Vesicles and Platelets

by Valeria Orrù, Francesca Virdis, Michele Marongiu, Valentina Serra, David Schlessinger, Marcella Devoto, Francesco Cucca and Edoardo Fiorillo

Int. J. Mol. Sci. 2023, 24(8), 7183; https://doi.org/10.3390/ijms24087183 - 13 Apr 2023

Viewed by 1204

Abstract

Extracellular vesicles (EVs) mediate cell interactions in biological processes, such as receptor activation or molecule transfer. Estimates of variation by age and sex have been limited by small sample size, and no report has assessed the contribution of genetic factors to levels of EVs. Here, we evaluated blood levels of 25 EV and 3 platelet traits in 974 individuals (933 genotyped) and reported the first genome-wide association study (GWAS) on levels of these traits. EV levels all decreased with age, whereas the trend for their surface markers was more heterogeneous. Platelets and CD31dim platelet EVs significantly increased in females compared to males, although CD31 expression on both platelets and platelet EVs decreased in females. Levels of the other EV subsets were similar between sexes. GWAS revealed three statistically significant genetic signals associated with EV levels in the F10 and GBP1 genes and in the intergenic region between LRIG1 and KBTBD8. These add to a signal in the 3′UTR of RHOF associated with CD31 expression on platelets that was previously found to be associated with other platelet traits. These findings suggest that EV formation is not a simple, constant adjunct of metabolism but is under both age-related and genetic control that can be independent of the regulation of the levels of the cells from which the EVs derive. Full article

(This article belongs to the Special Issue Understanding Metabolic Cross-Talk in Health and Disease)

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Review

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28 pages, 3504 KiB

Open AccessReview

An Overview of Inter-Tissue and Inter-Kingdom Communication Mediated by Extracellular Vesicles in the Regulation of Mammalian Metabolism

by Carlos Castaño, Anna Novials and Marcelina Párrizas

Int. J. Mol. Sci. 2023, 24(3), 2071; https://doi.org/10.3390/ijms24032071 - 20 Jan 2023

Cited by 2 | Viewed by 2520

Abstract

Obesity and type 2 diabetes are associated with defects of insulin action in different tissues or alterations in β-cell secretory capacity that may be triggered by environmental challenges, inadequate lifestyle choices, or an underlying genetic predisposition. In addition, recent data shows that obesity may also be caused by perturbations of the gut microbiota, which then affect metabolic function and energy homeostasis in the host. Maintenance of metabolic homeostasis in complex organisms such as mammals requires organismal-level communication, including between the different organs and the gut microbiota. Extracellular vesicles (EVs) have been identified in all domains of life and have emerged as crucial players in inter-organ and inter-kingdom crosstalk. Interestingly, EVs found in edible vegetables or in milk have been shown to influence gut microbiota or tissue function in mammals. Moreover, there is a multidirectional crosstalk mediated by EVs derived from gut microbiota and body organs that has implications for host health. Untangling this complex signaling network may help implement novel therapies for the treatment of metabolic disease. Full article

(This article belongs to the Special Issue Understanding Metabolic Cross-Talk in Health and Disease)

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