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Adipokines in Health and Diseases
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Adipokines in Health and Diseases

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 (30 June 2021) | Viewed by 22754

Special Issue Editor

Prof. Dr. Aurora Daniele

E-Mail Website
Guest Editor
Dipartimento di Scienze e Tecnologie Ambientali, Biologiche, Farmaceutiche, Università della Campania “Luigi Vanvitelli”, 81100 Caserta, Italy
Interests: adiponectin; nutrition; health and disease; physical activity; sport; metabolic diseases; immune disorders
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Adipose tissue is not a passive reservoir for energy storage; indeed, it produces several adipocytokines that act on different tissues and organs.

Adipocytokines have attracted increased attention when multiple and pleiotropic effects, in proliferative, inflammatory, and immune responses, show up. The involvement of adipocytokines in the abovementioned processes represents the starting point and the rationale for analyzing the involvement of adipose tissue in health conditions (e.g., different lifestyles, aging) and several diseases (e.g., metabolic diseases, malignancies, immune disorders).

For this Special Issue, we invite you to contribute with either an original research article or a comprehensive review focusing on the role of adipose tissue or adipokines in the regulation of health and disease or deepening our understanding of the molecular aspects that link this depot of tissues with other organs.

Prof. Aurora Daniele
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

  • adiponectin
  • adipose tissue
  • adipokines
  • nutrition
  • molecular pathways
  • biomarkers
  • health
  • disease

Related Special Issue

Published Papers (7 papers)

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Research

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16 pages, 6028 KiB  
Article
Adipokines as New Biomarkers of Immune Recovery: Apelin Receptor, RBP4 and ZAG Are Related to CD4+ T-Cell Reconstitution in PLHIV on Suppressive Antiretroviral Therapy
by Elena Yeregui, Jenifer Masip, Consuelo Viladés, Pere Domingo, Yolanda M. Pacheco, Julià Blanco, Josep Mallolas, Verónica Alba, Montserrat Vargas, Graciano García-Pardo, Eugènia Negredo, Montserrat Olona, Judit Vidal-González, Maria Peraire, Anna Martí, Laia Reverté, Fréderic Gómez-Bertomeu, Manuel Leal, Francesc Vidal, Joaquim Peraire and Anna Rulladd Show full author list remove Hide full author list
Int. J. Mol. Sci. 2022, 23(4), 2202; https://doi.org/10.3390/ijms23042202 - 17 Feb 2022
Cited by 3 | Viewed by 2108
Abstract
A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the [...] Read more.
A significant proportion of people living with HIV (PLHIV) who successfully achieve virological suppression fail to recover CD4+ T-cell counts. Since adipose tissue has been discovered as a key immune organ, this study aimed to assess the role of adipokines in the HIV immunodiscordant response. This is a multicenter prospective study including 221 PLHIV starting the first antiretroviral therapy (ART) and classified according to baseline CD4+ T-cell counts/µL (controls > 200 cells/µL and cases ≤ 200 cells/µL). Immune failure recovery was considered when cases did not reach more than 250 CD4+ T cells/µL at 144 weeks (immunological nonresponders, INR). Circulating adipokine concentrations were longitudinally measured using enzyme-linked immunosorbent assays. At baseline, apelin receptor (APLNR) and zinc-alpha-2-glycoprotein (ZAG) concentrations were significantly lower in INRs than in immunological responders (p = 0.043 and p = 0.034), and they remained lower during all ART follow-up visits (p = 0.044 and p = 0.028 for APLNR, p = 0.038 and p = 0.010 for ZAG, at 48 and 144 weeks, respectively). ZAG levels positively correlated with retinol-binding protein 4 (RBP4) levels (p < 0.01), and low circulating RBP4 concentrations were related to a low CD4+ T-cell gain (p = 0.018 and p = 0.039 at 48 and 144 weeks, respectively). Multiple regression adjusted for clinical variables and adipokine concentrations confirmed both low APLNR and RBP4 as independent predictors for CD4+ T cells at 144 weeks (p < 0.001). In conclusion, low APLNR and RBP4 concentrations were associated with poor immune recovery in treated PLHIV and could be considered predictive biomarkers of a discordant immunological response. Full article
(This article belongs to the Special Issue Adipokines in Health and Diseases)
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13 pages, 5205 KiB  
Article
Adiponectin and Leptin Exert Antagonizing Effects on HUVEC Tube Formation and Migration Modulating the Expression of CXCL1, VEGF, MMP-2 and MMP-9
by Ersilia Nigro, Marta Mallardo, Rita Polito, Filippo Scialò, Andrea Bianco and Aurora Daniele
Int. J. Mol. Sci. 2021, 22(14), 7516; https://doi.org/10.3390/ijms22147516 - 13 Jul 2021
Cited by 9 | Viewed by 2658
Abstract
Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on [...] Read more.
Adiponectin and leptin are two abundant adipokines with different properties but both described such as potent factors regulating angiogenesis. AdipoRon is a small-molecule that, binding to AdipoRs receptors, acts as an adiponectin agonist. Here, we investigated the effects of AdipoRon and leptin on viability, migration and tube formation on a human in vitro model, the human umbilical vein endothelial cells (HUVEC) focusing on the expression of the main endothelial angiogenic factors: hypoxia-inducible factor 1-alpha (HIF-1α), C-X-C motif chemokine ligand 1 (CXCL1), vascular endothelial growth factor A (VEGF-A), matrix metallopeptidase 2 (MMP-2) and matrix metallopeptidase 9 (MMP-9). Treatments with VEGF-A were used as positive control. Our data revealed that, at 24 h treatment, proliferation of HUVEC endothelial cells was not influenced by AdipoRon or leptin administration; after 48 h longer exposure time, the viability was negatively influenced by AdipoRon while leptin treatment and the combination of AdipoRon+leptin produced no effects. In addition, AdipoRon induced a significant increase in complete tubular structures together with induction of cell migration while, on the contrary, leptin did not induce tube formation and inhibited cell migration; interestingly, the co-treatment with both AdipoRon and leptin determined a significant decrease of the tubular structures and cell migration indicating that leptin antagonizes AdipoRon effects. Finally, we found that the effects induced by AdipoRon administration are accompanied by an increase in the expression of CXCL1, VEGF-A, MMP-2 and MMP-9. In conclusion, our data sustain the active role of adiponectin and leptin in linking adipose tissue with the vascular endothelium encouraging the further deepening of the role of adipokines in new vessel’s formation, to candidate them as therapeutic targets. Full article
(This article belongs to the Special Issue Adipokines in Health and Diseases)
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20 pages, 2299 KiB  
Article
Anti-Apoptotic Effect of Apelin in Human Placenta: Studies on BeWo Cells and Villous Explants from Third-Trimester Human Pregnancy
by Ewa Mlyczyńska, Małgorzata Myszka, Patrycja Kurowska, Monika Dawid, Tomasz Milewicz, Marta Bałajewicz-Nowak, Paweł Kowalczyk and Agnieszka Rak
Int. J. Mol. Sci. 2021, 22(5), 2760; https://doi.org/10.3390/ijms22052760 - 09 Mar 2021
Cited by 16 | Viewed by 2512
Abstract
Previously, we demonstrated the expression of apelin and G-protein-coupled receptor APJ in human placenta cell lines as well as its direct action on placenta cell proliferation and endocrinology. The objective of this study was to examine the effect of apelin on placenta apoptosis [...] Read more.
Previously, we demonstrated the expression of apelin and G-protein-coupled receptor APJ in human placenta cell lines as well as its direct action on placenta cell proliferation and endocrinology. The objective of this study was to examine the effect of apelin on placenta apoptosis in BeWo cells and villous explants from the human third trimester of pregnancy. The BeWo cells and villous explants were incubated with apelin (2 and 20 ng/mL) alone or with staurosporine for 24 to 72 h. First, we analysed the dose- and time-dependent effect of apelin on the expression of apoptotic factors on the mRNA level by real-time PCR and on the protein level using Western blot. Next, we checked caspase 3 and 7 activity by Caspase-Glo 3/7, DNA fragmentation by the Cell Death Detection ELISA kit and oxygen consumption by the MitoXpress-Xtra Oxygen Consumption assay. We found that apelin increased the expression of pro-survival and decreased proapoptotic factors on mRNA and protein levels in both BeWo cells and villous explants. Additionally, apelin inhibited caspase 3 and 7 activity and DNA fragmentation in staurosporine-induced apoptosis as also attenuated oxidative stress by increasing extracellular oxygen consumption. The antiapoptotic effect of apelin in BeWo cells was mediated by the APJ receptor and mitogen-activated protein kinase (ERK1/2/MAP3/1) and protein kinase B (AKT). The obtained results showed the antiapoptotic effect of apelin on trophoblast cells, suggesting its participation in the development of the placenta. Full article
(This article belongs to the Special Issue Adipokines in Health and Diseases)
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15 pages, 1717 KiB  
Article
Central Apolipoprotein A-IV Stimulates Thermogenesis in Brown Adipose Tissue
by Sydney Pence, Zachary LaRussa, Zhijun Shen, Min Liu, Karen T. Coschigano, Haifei Shi and Chunmin C. Lo
Int. J. Mol. Sci. 2021, 22(3), 1221; https://doi.org/10.3390/ijms22031221 - 27 Jan 2021
Cited by 5 | Viewed by 2149
Abstract
Stimulation of thermogenesis in brown adipose tissue (BAT) could have far-reaching health benefits in combatting obesity and obesity-related complications. Apolipoprotein A-IV (ApoA-IV), produced by the gut and the brain in the presence of dietary lipids, is a well-known short-term satiating protein. While our [...] Read more.
Stimulation of thermogenesis in brown adipose tissue (BAT) could have far-reaching health benefits in combatting obesity and obesity-related complications. Apolipoprotein A-IV (ApoA-IV), produced by the gut and the brain in the presence of dietary lipids, is a well-known short-term satiating protein. While our previous studies have demonstrated reduced diet-induced thermogenesis in ApoA-IV-deficient mice, it is unclear whether this reduction is due to a loss of peripheral or central effects of ApoA-IV. We hypothesized that central administration of ApoA-IV stimulates BAT thermogenesis and that sympathetic and sensory innervation is necessary for this action. To test this hypothesis, mice with unilateral denervation of interscapular BAT received central injections of recombinant ApoA-IV protein or artificial cerebrospinal fluid (CSF). The effects of central ApoA-IV on BAT temperature and thermogenesis in mice with unilateral denervation of the intrascapular BAT were monitored using transponder probe implantation, qPCR, and immunoblots. Relative to CSF, central administration of ApoA-IV significantly increased temperature and UCP expression in BAT. However, all of these effects were significantly attenuated or prevented in mice with unilateral denervation. Together, these results clearly demonstrate that ApoA-IV regulates BAT thermogenesis centrally, and this effect is mediated through sympathetic and sensory nerves. Full article
(This article belongs to the Special Issue Adipokines in Health and Diseases)
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Review

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28 pages, 2942 KiB  
Review
Adiponectin Deregulation in Systemic Autoimmune Rheumatic Diseases
by Neža Brezovec, Katja Perdan-Pirkmajer, Saša Čučnik, Snežna Sodin-Šemrl, John Varga and Katja Lakota
Int. J. Mol. Sci. 2021, 22(8), 4095; https://doi.org/10.3390/ijms22084095 - 15 Apr 2021
Cited by 12 | Viewed by 3952
Abstract
Deregulation of adiponectin is found in systemic autoimmune rheumatic diseases (SARDs). Its expression is downregulated by various inflammatory mediators, but paradoxically, elevated serum levels are present in SARDs with high inflammatory components, such as rheumatoid arthritis and systemic lupus erythematosus. Circulating adiponectin is [...] Read more.
Deregulation of adiponectin is found in systemic autoimmune rheumatic diseases (SARDs). Its expression is downregulated by various inflammatory mediators, but paradoxically, elevated serum levels are present in SARDs with high inflammatory components, such as rheumatoid arthritis and systemic lupus erythematosus. Circulating adiponectin is positively associated with radiographic progression in rheumatoid arthritis as well as with cardiovascular risks and lupus nephritis in systemic lupus erythematosus. However, in SARDs with less prominent inflammation, such as systemic sclerosis, adiponectin levels are low and correlate negatively with disease activity. Regulators of adiponectin gene expression (PPAR-γ, Id3, ATF3, and SIRT1) and inflammatory cytokines (interleukin 6 and tumor necrosis factor α) are differentially expressed in SARDs and could therefore influence total adiponectin levels. In addition, anti-inflammatory therapy could also have an impact, as tocilizumab treatment is associated with increased serum adiponectin. However, anti-tumor necrosis factor α treatment does not seem to affect its levels. Our review provides an overview of studies on adiponectin levels in the bloodstream and other biological samples from SARD patients and presents some possible explanations why adiponectin is deregulated in the context of therapy and gene regulation. Full article
(This article belongs to the Special Issue Adipokines in Health and Diseases)
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29 pages, 3196 KiB  
Review
The Inflammatory Profile of Obesity and the Role on Pulmonary Bacterial and Viral Infections
by Franziska Hornung, Julia Rogal, Peter Loskill, Bettina Löffler and Stefanie Deinhardt-Emmer
Int. J. Mol. Sci. 2021, 22(7), 3456; https://doi.org/10.3390/ijms22073456 - 26 Mar 2021
Cited by 21 | Viewed by 4675
Abstract
Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of [...] Read more.
Obesity is a globally increasing health problem, entailing diverse comorbidities such as infectious diseases. An obese weight status has marked effects on lung function that can be attributed to mechanical dysfunctions. Moreover, the alterations of adipocyte-derived signal mediators strongly influence the regulation of inflammation, resulting in chronic low-grade inflammation. Our review summarizes the known effects regarding pulmonary bacterial and viral infections. For this, we discuss model systems that allow mechanistic investigation of the interplay between obesity and lung infections. Overall, obesity gives rise to a higher susceptibility to infectious pathogens, but the pathogenetic process is not clearly defined. Whereas, viral infections often show a more severe course in obese patients, the same patients seem to have a survival benefit during bacterial infections. In particular, we summarize the main mechanical impairments in the pulmonary tract caused by obesity. Moreover, we outline the main secretory changes within the expanded adipose tissue mass, resulting in chronic low-grade inflammation. Finally, we connect these altered host factors to the influence of obesity on the development of lung infection by summarizing observations from clinical and experimental data. Full article
(This article belongs to the Special Issue Adipokines in Health and Diseases)
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18 pages, 3825 KiB  
Review
Adiponectin as a Potential Biomarker for Pregnancy Disorders
by Carmen Pheiffer, Stephanie Dias, Babalwa Jack, Nompumelelo Malaza and Sumaiya Adam
Int. J. Mol. Sci. 2021, 22(3), 1326; https://doi.org/10.3390/ijms22031326 - 29 Jan 2021
Cited by 18 | Viewed by 3786
Abstract
Adiponectin is an adipocyte-derived hormone that plays a critical role in energy homeostasis, mainly attributed to its insulin-sensitizing properties. Accumulating studies have reported that adiponectin concentrations are decreased during metabolic diseases, such as obesity and type 2 diabetes, with an emerging body of [...] Read more.
Adiponectin is an adipocyte-derived hormone that plays a critical role in energy homeostasis, mainly attributed to its insulin-sensitizing properties. Accumulating studies have reported that adiponectin concentrations are decreased during metabolic diseases, such as obesity and type 2 diabetes, with an emerging body of evidence providing support for its use as a biomarker for pregnancy complications. The identification of maternal factors that could predict the outcome of compromised pregnancies could act as valuable tools that allow the early recognition of high-risk pregnancies, facilitating close follow-up and prevention of pregnancy complications in mother and child. In this review we consider the role of adiponectin as a potential biomarker of disorders associated with pregnancy. We discuss common disorders associated with pregnancy (gestational diabetes mellitus, preeclampsia, preterm birth and abnormal intrauterine growth) and highlight studies that have investigated the potential of adiponectin to serve as biomarkers for these disorders. We conclude the review by recommending strategies to consider for future research. Full article
(This article belongs to the Special Issue Adipokines in Health and Diseases)
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