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14 pages, 2157 KiB

Open AccessArticle

Inflammation-Involved Proteins in Blood Serum of Cataract Patients—A Preliminary Study

by Paweł Sutkowy, Hanna Lesiewska, Alina Woźniak and Grażyna Malukiewicz

Biomedicines 2023, 11(10), 2607; https://doi.org/10.3390/biomedicines11102607 - 22 Sep 2023

Cited by 3 | Viewed by 1295

Abstract

Approximately 50% of all global blindness is caused by cataract in adults aged ≥50 years. The mechanisms of the disease are most arguably related to a redox imbalance and inflammation; therefore, the aim of the study was to evaluate the processes associated with [...] Read more.

Approximately 50% of all global blindness is caused by cataract in adults aged ≥50 years. The mechanisms of the disease are most arguably related to a redox imbalance and inflammation; therefore, the aim of the study was to evaluate the processes associated with inflammation in cataract patients. Twenty-four patients aged 22–60 years (62.5% females) participated in the study, with 33 controls aged 28–60 years (66.7% females). Venous blood serum of the subjects was examined for alpha 1-antitrypsin, as well as selected lysosomal enzymes and adipokines. The activities of lysosomal enzymes, as well as the activity of alpha 1-antitrypsin and the concentrations of c-reactive protein and leptin, were similar in the patients versus the controls. The concentrations of interleukin 6 and resistin were lower, in turn, whereas omentin-1 and adiponectin were higher. Moreover, the study revealed the existence of many linear relationships between the parameters, including multiple linear regression, especially gender-wise. No systemic inflammation was probably noted in the cataract patients tested; nevertheless, the deregulation of adiponectin, omentin-1 and resistin secretion was observed. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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13 pages, 1868 KiB

Open AccessArticle

Association between TGFβ1 Levels in Cord Blood and Weight Progress in the First Year of Life

by Noura Kabbani, Holger Stepan, Matthias Blüher, Thomas Ebert, Ronny Baber, Mandy Vogel, Wieland Kiess, Michael Stumvoll, Jana Breitfeld, Ulrike Lössner, Anke Tönjes and Susanne Schrey-Petersen

Biomedicines 2023, 11(8), 2220; https://doi.org/10.3390/biomedicines11082220 - 8 Aug 2023

Viewed by 1295

Abstract

Transforming growth factor beta-1 (TGFβ1) is an adipokine secreted from adipose tissue, placental tissue and immune cells with a role in cell proliferation, cell apoptosis and angiogenic proliferation. The role of TGFβ1 in pregnancy and child growth and the source of cord TGFβ1 [...] Read more.

Transforming growth factor beta-1 (TGFβ1) is an adipokine secreted from adipose tissue, placental tissue and immune cells with a role in cell proliferation, cell apoptosis and angiogenic proliferation. The role of TGFβ1 in pregnancy and child growth and the source of cord TGFβ1 are yet unknown. In this study, we sought to clarify the correlation of TGFβ1 levels with parameters of intrauterine growth and child growth during the first year of life, and to determine whether their source is primarily of fetal or maternal origin. Serum samples and anthropometric measurements were obtained from the LIFE Child cohort of 79 healthy mother–child pairs. Measurements were conducted using enzyme-linked immunosorbent assays. Statistical analyses including Mann–Whitney U-test, correlation analyses and linear regression analyses were performed using GraphPad Prism and R. TGFβ1 levels were significantly higher in cord than in maternal serum, suggesting a fetal origin. Multivariate regression analyses revealed strong positive associations between cord TGFβ1 levels at birth and child weight at U6. Furthermore, cord TGFβ1 was significantly correlated with child weight at approximately one year of age. An increase of 10,000 pg/mL in cord TGFβ1 concentrations at birth was associated with a higher body weight of 201 g at roughly one year of age when adjusted for sex. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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13 pages, 1289 KiB

Open AccessArticle

GLP-1 Increases Circulating Leptin Levels in Truncal Vagotomized Rats

by Tiago Morais, Sofia S. Pereira, Sara Andrade, Diogo Neves, Marta Guimarães, Mário Nora, Marcos C. Carreira, Felipe F. Casanueva and Mariana P. Monteiro

Biomedicines 2023, 11(5), 1322; https://doi.org/10.3390/biomedicines11051322 - 28 Apr 2023

Cited by 2 | Viewed by 2079

Abstract

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls [...] Read more.

GLP-1 is a gastro-intestinal hormone acting within the gut/brain axis for energy balance regulation. We aimed to evaluate the role of the vagus nerve in whole-body energy homeostasis and in mediating GLP-1 effects. For this, rats submitted to truncal vagotomy and sham-operated controls underwent a comprehensive evaluation, including eating behavior, body weight, percentage of white (WAT) and brown adipose tissue (BAT), resting energy expenditure (REE) and acute response to GLP-1. Truncal vagotomized rats had significantly lower food intake, body weight, body weight gain, WAT and BAT, with a higher BAT/WAT ratio, but no significant difference in REE when compared to controls. Vagotomized rats also had significantly higher fasting ghrelin and lower glucose and insulin levels. After GLP-1 administration, vagotomized rats depicted a blunted anorexigenic response and higher plasma leptin levels, as compared to controls. However, in vitro stimulation of VAT explants with GLP-1 resulted in no significant changes in leptin secretion. In conclusion, the vagus nerve influences whole-body energy homeostasis by modifying food intake, body weight and body composition and by mediating the GLP-1 anorectic response. The higher leptin levels in response to acute GLP-1 administration observed after truncal vagotomy suggest the existence of a putative GLP-1-leptin axis that relies on the integrity of gut–brain vagal pathway. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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10 pages, 1242 KiB

Open AccessEditor’s ChoiceArticle

Dihydrotestosterone, and Not Testosterone, Enhances the LPS-Induced Inflammatory Cytokine Gene Expression in Human Adipocytes

by Angelo Di Vincenzo, Marnie Granzotto, Marika Crescenzi, Vincenzo Vindigni, Roberto Vettor and Marco Rossato

Biomedicines 2023, 11(4), 1194; https://doi.org/10.3390/biomedicines11041194 - 17 Apr 2023

Cited by 3 | Viewed by 2470

Abstract

Background: The development of obesity-related complications lies in the low-grade inflammatory state consequent to adipocyte dysfunction. The direct involvement of sex hormones in adipose tissue inflammation has been previously suggested, but the evidence is scarce. In this study, we evaluated the effects of [...] Read more.

Background: The development of obesity-related complications lies in the low-grade inflammatory state consequent to adipocyte dysfunction. The direct involvement of sex hormones in adipose tissue inflammation has been previously suggested, but the evidence is scarce. In this study, we evaluated the effects of sex steroids on the in-vitroexpression of inflammatory mediators in human-derived adipocytes before and after lipopolysaccharide (LPS) exposure. Methods: Human adipocytes were differentiated from the vascular stromal fraction of adipose tissue samples of subjects undergoing abdominoplasty. We evaluated MCP-1, IL-1β, IL-6, and TNF-α gene expression in the presence of the main sex steroids, testosterone (T), and 17β-estradiol (E). Furthermore, we analyzed the effects of adipocytes exposure to the non-aromatizable androgen dihydrotestosterone (DHT), together with the effects of adipocytes pre-incubation with the aromatase inhibitor anastrozole alone (A), and in combination with T (A/T) before incubation with LPS. Results: DHT, but not T, significantly enhanced the LPSinduction of MCP-1, IL-1β, IL-6, and TNF-α. Intriguingly, the exposure of adipocytes with A/T dramatically increased the LPS-induced expression of all considered inflammatory cytokines, even more than a hundred-fold. Conclusions: DHT and A/T dramatically enhance LPS-induced inflammatory cytokine expression in human-derived adipocytes. These results confirm the involvement of sex hormones in adipose tissue inflammation, suggesting a specific role for non-aromatizable androgens as the amplificatory sex hormones of the inflammatory response. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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10 pages, 696 KiB

Open AccessArticle

Investigating Urine Biomarkers in Detrusor Underactivity and Detrusor Overactivity with Detrusor Underactivity Patients

by Yuan-Hong Jiang, Jia-Fong Jhang, Ya-Hui Wu and Hann-Chorng Kuo

Biomedicines 2023, 11(4), 1191; https://doi.org/10.3390/biomedicines11041191 - 17 Apr 2023

Cited by 7 | Viewed by 1428

Abstract

Bladder inflammation and tissue hypoxia were considered important pathognomonic bladder features in detrusor underactivity (DU) and detrusor overactivity (DO) patients. This study investigated urine inflammatory and oxidative stress biomarker levels in DU and DO with DU (DO-DU) patients. Urine samples were collected from [...] Read more.

Bladder inflammation and tissue hypoxia were considered important pathognomonic bladder features in detrusor underactivity (DU) and detrusor overactivity (DO) patients. This study investigated urine inflammatory and oxidative stress biomarker levels in DU and DO with DU (DO-DU) patients. Urine samples were collected from 50 DU and 18 DO-DU patients, as well as 20 controls. The targeted analytes included three oxidative stress biomarkers (8-OHdG, 8-isoprostane, and total antioxidant capacity [TAC]) and 33 cytokines. DU and DO-DU patients had different urine biomarker profiles from controls, including 8-OHdG, PGE2, EGF, TNFα, IL-1β, IL-5, IL-6, IL-8, IL-10, IL-17A, and CXCL10. Controlling for age and sex, multivariate logistic-regression models revealed that 8-OHdG, PGE2, EGF, IL-5, IL-8, IL-10, and TAC were significant biomarkers for diagnosing DU. In DU patients, urine TAC and PGE₂ levels were positively correlated with detrusor voiding pressure. In DO-DU patients, urine 8-OHdG, PGE₂, IL-6, IL-10, and MIP-1α levels were positively correlated with maximal urinary flow rate, while urine IL-5, IL-10, and MIP-1α were negatively correlated with the first sensation of bladder filling. Urine inflammatory and oxidative stress biomarker analysis provides a non-invasive and convenient approach for important clinical information in DU and DO-DU patients. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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13 pages, 1257 KiB

Open AccessArticle

The Association of Leptin with Left Ventricular Hypertrophy in End-Stage Kidney Disease Patients on Dialysis

by Susana Coimbra, Cristina Catarino, Maria Sameiro Faria, José Pedro L. Nunes, Susana Rocha, Maria João Valente, Petronila Rocha-Pereira, Elsa Bronze-da-Rocha, Nuno Bettencourt, Ana Beco, Sofia Homem de Melo Marques, José Gerardo Oliveira, José Madureira, João Carlos Fernandes, Vasco Miranda, Luís Belo and Alice Santos-Silva

Biomedicines 2023, 11(4), 1026; https://doi.org/10.3390/biomedicines11041026 - 27 Mar 2023

Cited by 1 | Viewed by 2127

Abstract

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) [...] Read more.

Left ventricular hypertrophy (LVH) is a common cardiovascular complication in end-stage kidney disease (ESKD) patients. We aimed at studying the association of LVH with adiponectin and leptin levels, cardiovascular stress/injury biomarkers and nutritional status in these patients. We evaluated the LV mass (LVM) and calculated the LVM index (LVMI) in 196 ESKD patients on dialysis; the levels of hemoglobin, calcium, phosphorus, parathyroid hormone, albumin, adiponectin, leptin, N-terminal pro B-type natriuretic peptide (NT-proBNP) and growth differentiation factor (GDF)-15 were analyzed. ESKD patients with LVH (n = 131) presented higher NT-proBNP and GDF-15, lower hemoglobin and, after adjustment for gender, lower leptin levels compared with non-LVH patients. LVH females also showed lower leptin than the non-LVH female group. In the LVH group, LVMI presented a negative correlation with leptin and a positive correlation with NT-proBNP. Leptin emerged as an independent determinant of LVMI in both groups, and NT-proBNP in the LVH group. Low hemoglobin and leptin and increased calcium, NT-proBNP and dialysis vintage are associated with an increased risk of developing LVH. In ESKD patients on dialysis, LVH is associated with lower leptin values (especially in women), which are negatively correlated with LVMI, and with higher levels of biomarkers of myocardial stress/injury. Leptin and NT-proBNP appear as independent determinants of LVMI; dialysis vintage, hemoglobin, calcium, NT-proBNP and leptin emerged as predicting markers for LVH development. Further studies are needed to better understand the role of leptin in LVH in ESKD patients. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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14 pages, 296 KiB

Open AccessEditor’s ChoiceArticle

Effect of Lifestyle Interventions during Pregnancy on Maternal Leptin, Resistin and Offspring Weight at Birth and One Year of Life

by Nina Ferrari, Nikola Schmidt, Lisa Schmidt, Waltraut M. Merz, Konrad Brockmeier, Jörg Dötsch, Inga Bae-Gartz, Esther Mahabir and Christine Joisten

Biomedicines 2023, 11(2), 447; https://doi.org/10.3390/biomedicines11020447 - 3 Feb 2023

Viewed by 1692

Abstract

Lifestyle during pregnancy impacts the health of the mother and child. However, the extent to which physical activity affects maternal biomarkers and factors that might influence birth weight remains unclear. We analysed data from two lifestyle interventions in which the effects of an [...] Read more.

Lifestyle during pregnancy impacts the health of the mother and child. However, the extent to which physical activity affects maternal biomarkers and factors that might influence birth weight remains unclear. We analysed data from two lifestyle interventions in which the effects of an exercise programme (2x/week, 60–90 min) on the course of pregnancy with regard to adipokines and offspring were evaluated. A total of 70 women participated in this study (45, intervention group; 25, control group). Anthropometric data and maternal fasting serum leptin and resistin levels were measured at three time points (approximately 14th (T1), 24th (T2), and 36th (T3) weeks of gestation). Neonatal/child data were retrieved from screening examinations. Independent of the intervention, we found a positive correlation between the fat mass at T1 and both leptin and resistin levels at all time points. Leptin level was significantly higher in the control group at T3; however, no differences between the groups were found for resistin. The birth weight was influenced by the birth length, fat mass at T1/T3, and resistin level at T2. The BMI-SDS at one year of age was influenced by maternal fat-free mass at T3 and resistin at T1/T2. Even if these results can only be interpreted cautiously, lifestyle interventions during pregnancy are important in promoting maternal and child health. Further randomised controlled trials and translational studies are warranted to clarify the underlying mechanisms. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

14 pages, 1304 KiB

Open AccessArticle

Secreted Frizzled Related Protein 5 (SFRP5) Serum Levels Are Decreased in Critical Illness and Sepsis and Are Associated with Short-Term Mortality

by Philipp Hohlstein, Jonathan F. Brozat, Julia Schuler, Samira Abu Jhaisha, Maike R. Pollmanns, Lukas Bündgens, Theresa H. Wirtz, Eray Yagmur, Karim Hamesch, Ralf Weiskirchen, Frank Tacke, Christian Trautwein and Alexander Koch

Biomedicines 2023, 11(2), 313; https://doi.org/10.3390/biomedicines11020313 - 22 Jan 2023

Cited by 5 | Viewed by 1863

Abstract

Sepsis is a major health burden with insufficiently understood mechanisms of inflammation and immune paralysis, leading to a life-threatening critical illness. The secreted frizzled related protein 5 (SFRP5) acts as an anti-inflammatory adipokine by antagonizing the Wnt5a pathway. The aim of this study [...] Read more.

Sepsis is a major health burden with insufficiently understood mechanisms of inflammation and immune paralysis, leading to a life-threatening critical illness. The secreted frizzled related protein 5 (SFRP5) acts as an anti-inflammatory adipokine by antagonizing the Wnt5a pathway. The aim of this study was to elucidate the role of SFRP5 in critical illness and sepsis and to determine its value as a prognostic biomarker for mortality. We analyzed SFRP5 serum concentrations of 223 critically ill patients at admission to a medical intensive care unit (ICU) and compared those to 24 healthy individuals. SFRP5 serum concentrations were significantly decreased in critical illness as compared to healthy controls (24.66 vs. 100 ng/mL, p = 0.029). Even lower serum concentrations were found in septic as compared to nonseptic critically ill patients (19.21 vs. 32.83 ng/mL, p = 0.031). SFRP5 concentrations correlated with liver disease, age, anti-inflammation, and metabolic parameters. Furthermore, patients with sepsis recovered levels of SFRP5 in the first week of ICU treatment. SFRP5 levels at admission predicted short-term mortality in critically ill but not in septic patients. This study points to the role of the anti-inflammatory mediator SFRP5 not only in sepsis but also in nonseptic critically ill patients and associates high levels of SFRP5 to worse outcomes, predominantly in nonseptic critically ill patients. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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9 pages, 1738 KiB

Open AccessArticle

The Adipokine Visfatin Modulates Cancer Stem Cell Properties in Triple-Negative Breast Cancer

by Yi-Fen Chiang, Ko-Chieh Huang, Hsin-Yuan Chen, Tsui-Chin Huang, Mohamed Ali, Hsin-Yi Chang, Tzong-Ming Shieh, Yin-Hwa Shih, Kai-Lee Wang, Yun-Ju Huang, Cheng-Pei Chung and Shih-Min Hsia

Biomedicines 2023, 11(2), 297; https://doi.org/10.3390/biomedicines11020297 - 20 Jan 2023

Cited by 3 | Viewed by 2255

Abstract

Obesity is a cancer progression risk factor; excessive adipocytes increase adipokine secretion. Visfatin, a novel adipokine highly expressed in cancer patients, is related to breast cancer risk. The modulation of nicotinamide adenine dinucleotide (NAD+) metabolism and the induction of a tumorigenic environment plays [...] Read more.

Obesity is a cancer progression risk factor; excessive adipocytes increase adipokine secretion. Visfatin, a novel adipokine highly expressed in cancer patients, is related to breast cancer risk. The modulation of nicotinamide adenine dinucleotide (NAD+) metabolism and the induction of a tumorigenic environment plays a vital role in cancer progression. Among cancer cell types, cancer stem-like cells (CSCs) with self-renewal and chemotherapy-resistance abilities could modulate tumor progression and cancer recurrence ability. In this study, we focused on visfatin’s modulation effect on stemness-related properties using the high-malignancy breast cancer cell line MDA-MB-231 in in vitro and in vivo studies. Visfatin treatment significantly increased both the sphere number and sphere diameter and increased the protein expression of NANOG homeobox (NANOG), sex-determining region Y-box 2 (SOX2), and octamer-binding transcription factor 4 (OCT4), as well as SIRT1 protein levels. The serum angiogenesis marker VEGF and extracellular nicotinamide phosphoribosyl transferase (NAMPT, visfatin) were induced after visfatin treatment, increasing the stemness and angiogenesis environment, which were significantly reduced by the visfatin inhibitor FK866. Our results demonstrate that the visfatin-activated SIRT–SOX2 axis promotes triple-negative breast cancer stemness and enriches the tumorigenic microenvironment. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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18 pages, 4118 KiB

Open AccessArticle

Increasing Adiponectin Signaling by Sub-Chronic AdipoRon Treatment Elicits Antidepressant- and Anxiolytic-Like Effects Independent of Changes in Hippocampal Plasticity

by Douglas A. Formolo, Thomas H. Lee, Jiasui Yu, Kangguang Lin, Gang Chen, Georg S. Kranz and Suk-Yu Yau

Biomedicines 2023, 11(2), 249; https://doi.org/10.3390/biomedicines11020249 - 18 Jan 2023

Cited by 7 | Viewed by 2201

Abstract

(1) Background: Adiponectin is an adipocyte-secreted hormone that has antidepressant- and anxiolytic-like effects in preclinical studies. Here, we investigated the antidepressant- and anxiolytic-like effects of sub-chronic treatment with AdipoRon, an adiponectin receptor agonist, and its potential linkage to changes in hippocampal adult neurogenesis [...] Read more.

(1) Background: Adiponectin is an adipocyte-secreted hormone that has antidepressant- and anxiolytic-like effects in preclinical studies. Here, we investigated the antidepressant- and anxiolytic-like effects of sub-chronic treatment with AdipoRon, an adiponectin receptor agonist, and its potential linkage to changes in hippocampal adult neurogenesis and synaptic plasticity. (2) Methods: Different cohorts of wild-type C57BL/6J and CamKIIα-Cre male mice were treated with sub-chronic (7 days) AdipoRon, followed by behavioral, molecular, and electrophysiological experiments. (3) Results: 7-day AdipoRon treatment elicited antidepressant- and anxiolytic-like effects but did not affect hippocampal neurogenesis. AdipoRon treatment reduced hippocampal brain-derived neurotrophic factor (BDNF) levels, neuronal activation in the ventral dentate gyrus, and long-term potentiation of the perforant path. The knockdown of N-methyl-D-aspartate (NMDA) receptor subunits GluN2A and GluN2B in the ventral hippocampus did not affect the antidepressant- and anxiolytic-like effects of AdipoRon. (4) Conclusions: Increasing adiponectin signaling through sub-chronic AdipoRon treatment results in antidepressant- and anxiolytic-like effects independent of changes in hippocampal structural and synaptic function. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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14 pages, 1645 KiB

Open AccessArticle

Chemerin as a Potential Marker of Resolution of Inflammation in COVID-19 Infection

by Joanna Sulicka-Grodzicka, Andrzej Surdacki, Marcin Surmiak, Marek Sanak, Barbara Wizner, Wojciech Sydor, Monika Bociąga-Jasik, Magdalena Strach, Mariusz Korkosz, Lubomir Skladany, Ivica Grgurevic, Kristian Podrug and Michał Kukla

Biomedicines 2022, 10(10), 2462; https://doi.org/10.3390/biomedicines10102462 - 1 Oct 2022

Cited by 11 | Viewed by 1964

Abstract

Chemerin is one of the specialized pro-resolving mediators that participate in the early phase of inflammation and contribute to the initiation of the pro-resolving response. There is a paucity of data regarding the time course of chemerin during acute infections. We aimed to [...] Read more.

Chemerin is one of the specialized pro-resolving mediators that participate in the early phase of inflammation and contribute to the initiation of the pro-resolving response. There is a paucity of data regarding the time course of chemerin during acute infections. We aimed to evaluate the sequence of inflammatory responses in the acute COVID-19 phase throughout onset and resolution of inflammation. We evaluated changes in selected biomarkers in COVID-19 survivors on the 7-day and 28-day follow up. Chemerin was lower in patients with baseline moderate/severe disease at day 7 compared with asymptomatic patients and individuals with mild illness (7265 [5526–9448] vs. 8730 [6888–11,058] pg/mL; p = 0.03). Only in patients with moderate/severe disease, but not in those with mild symptoms, were chemerin concentrations decreased one week after infection onset compared with baseline (7265 [5526–9448] vs. 8866 [6383–10,690] pg/mL; p < 0.05) with a subsequent increase on the 28-day follow up (9313 [7353–11,033] pg/mL; p < 0.05). Resolution of inflammation in the group of moderate/severe SARS-CoV2 infection was associated with increasing serum concentrations of chemerin, contrary to pro-inflammatory cytokines and adipokines (pentraxin 3, TNFα, resistin, leptin). A similar pattern of angiopoietin-2 dynamics may suggest signs of enhanced vascularization as a consequence of acute SARS-CoV2 infection. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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11 pages, 1741 KiB

Open AccessArticle

Resistin Modulates the Functional Activity of Colostral Macrophages from Mothers with Obesity and Diabetes

by Letícia Damas Leão Dalcin, Danny Laura Gomes Fagundes-Triches, Adriele Ataides de Queiroz, André Henrique Furtado Torres, Danielle Cristina Honorio França, Tatiane Araújo Soares, Luana Cristina da Silva Ramos, Carla Roberta Silva Souza Antônio, Mahmi Fujimori, Eduardo Luzia França and Adenilda Cristina Honorio-França

Biomedicines 2022, 10(10), 2332; https://doi.org/10.3390/biomedicines10102332 - 20 Sep 2022

Cited by 3 | Viewed by 1551

Abstract

Background: Obesity and diabetes are major public health problems. Resistin is an adipokine that links the two diseases. There are few reports regarding colostrum cells and resistin from mothers with obesity and diabetes. Thus, this study aimed to determine the functional activity of [...] Read more.

Background: Obesity and diabetes are major public health problems. Resistin is an adipokine that links the two diseases. There are few reports regarding colostrum cells and resistin from mothers with obesity and diabetes. Thus, this study aimed to determine the functional activity of macrophages present in the breast milk and colostrum of diabetic mothers with obesity and the effects of resistin on these cells. Methods: The women were divided according to BMI and glycemic status into normal weight non-diabetic, obese non-diabetic, normal weight type 2 diabetic, or obese type 2 diabetic groups. ELISA determined the resistin in colostrum. The cell subsets and apoptosis were determined by flow cytometry and the functional activity of cells by fluorescence microscopy. Results: The resistin levels were higher in the colostrum from diabetic mothers with obesity. The frequencies of CD14⁺ cells and cells expressing CD95⁺, independent of resistin treatment, were higher in the colostrum from diabetic mothers with obesity. The frequency of cells expressing CD14⁺CD95⁺ was higher in cells not treated with resistin in the colostrum from diabetic mothers with obesity. Apoptosis, irrespective of the presence of resistin, increased, whereas microbicidal activity decreased in cells from diabetic mothers with obesity. Conclusion: The data suggest that hyperglycemia associated with low-grade inflammation caused by obesity affects the percentage of cells expressing CD14⁺CD95⁺, death by apoptosis, and microbicidal indices; meanwhile, resistin restored the microbicidal activity of colostrum cells. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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14 pages, 3685 KiB

Open AccessArticle

Chronic Central Leptin Infusion Promotes an Anti-Inflammatory Cytokine Profile Related to the Activation of Insulin Signaling in the Gastrocnemius of Male Rats

by Vicente Barrios, Santiago Guerra-Cantera, Álvaro Martín-Rivada, Sandra Canelles, Ana Campillo-Calatayud, Eduardo Arilla-Ferreiro, Laura M. Frago, Julie A. Chowen and Jesús Argente

Biomedicines 2022, 10(7), 1465; https://doi.org/10.3390/biomedicines10071465 - 21 Jun 2022

Cited by 2 | Viewed by 1954

Abstract

Leptin is involved in the modulation of insulin signaling in peripheral tissues, being closely associated with changes in lipid metabolism. This adipokine modifies inflammatory pathways that can interact with insulin targets in peripheral organs; however, the mechanisms remain unclear. Inflammatory and insulin signaling [...] Read more.

Leptin is involved in the modulation of insulin signaling in peripheral tissues, being closely associated with changes in lipid metabolism. This adipokine modifies inflammatory pathways that can interact with insulin targets in peripheral organs; however, the mechanisms remain unclear. Inflammatory and insulin signaling targets, cytokines, adiponectin, irisin and non-esterified fatty acid (NEFA) levels and enzymes of fatty acid anabolism were studied in the gastrocnemius of chronic centrally infused leptin (L), pair-fed and control rats. The phosphorylation of signal transducer and activator of transcription 3 (STAT3) and c-Jun N-terminal kinase (JNK) was reduced in L rats (59% and 58%, respectively). The phosphorylation of the insulin receptor and Akt and adiponectin and irisin content was increased in L rats (154%, 157%, 308% and 329%, respectively). The levels of glucose-6-phosphate dehydrogenase, the mRNA content of acetyl Co-A carboxylase and NEFA concentrations were diminished in the muscles of L rats (59%, 50% and 61%, respectively). The activation of JNK correlated positively with STAT3 phosphorylation, tumoral necrosis factor-α and NEFA and negatively with irisin and Akt phosphorylation. These data suggest that the activation of insulin signaling targets and a decrease in NEFA content are associated with a reduction in muscle inflammation parameters, suggesting that leptin may integrate these pathways. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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Review

Jump to: Research

17 pages, 968 KiB

Open AccessReview

The Role of Adipokines in Tumor Progression and Its Association with Obesity

by Jae Won Kim, Jun Hyeok Kim and Yoon Jae Lee

Biomedicines 2024, 12(1), 97; https://doi.org/10.3390/biomedicines12010097 - 3 Jan 2024

Cited by 12 | Viewed by 2727

Abstract

Obesity is a well-established risk factor for various malignancies and emerging evidence suggests that adipokines play a pivotal role in linking excess adiposity to tumorigenesis. Adipokines are bioactive molecules secreted by adipose tissue and their altered expression in obesity contributes to a pro-inflammatory, [...] Read more.

Obesity is a well-established risk factor for various malignancies and emerging evidence suggests that adipokines play a pivotal role in linking excess adiposity to tumorigenesis. Adipokines are bioactive molecules secreted by adipose tissue and their altered expression in obesity contributes to a pro-inflammatory, pro-angiogenic, and growth-promoting microenvironment conducive to tumorigenesis. Leptin, a key adipokine, activates survival and proliferative signaling pathways whereas adiponectin exhibits tumor-suppressive effects by inducing apoptosis and cell cycle arrest. Visfatin has also been documented to promote tumor growth, angiogenesis, migration, and invasion. Moreover, emerging studies suggest that adipokines, such as resistin, apelin, and chemerin, which are overexpressed in obesity, may also possess oncogenic functions. Despite advancements in our understanding of the roles of individual adipokines in cancer, the intricate interplay and crosstalk between adipokines, tumor cells, and the tumor microenvironment remain complex and multifaceted. This review highlights the evolving knowledge of how adipokines contribute to obesity-related tumorigenesis, shedding light on the potential of targeting adipokine signaling pathways as a novel therapeutic approach for obesity-associated cancers. Further research on the specific mechanisms and interactions between adipokines and tumor cells is crucial for a comprehensive understanding of obesity-associated cancer pathogenesis. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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15 pages, 2850 KiB

Open AccessReview

Linking Adiponectin and Its Receptors to Age-Related Macular Degeneration (AMD)

by Mayank Choubey, Munichandra B. Tirumalasetty, Nalini S. Bora and Puran S. Bora

Biomedicines 2023, 11(11), 3044; https://doi.org/10.3390/biomedicines11113044 - 14 Nov 2023

Cited by 2 | Viewed by 2568

Abstract

In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged [...] Read more.

In recent years, there has been a captivating focus of interest in elucidating the intricate crosstalk between adiponectin (APN), a versatile fat-associated adipokine and ocular pathologies. Unveiling the intricate relationship between adipocytokine APN and its receptors (AdipoRs) with aging eye disorders has emerged as a fascinating frontier in medical research. This review article delves into this connection, illuminating the hidden influence of APN on retinal health. This comprehensive review critically examines the latest findings and breakthroughs that underscore the pivotal roles of APN/AdipoRs signaling in maintaining ocular homeostasis and protecting against eye ailments. Here, we meticulously explore the intriguing mechanisms by which APN protein influences retinal function and overall visual acuity. Drawing from an extensive array of cutting-edge studies, the article highlights APN’s multifaceted functions, ranging from anti-inflammatory properties and oxidative stress reduction to angiogenic regulation within retinal and macula tissues. The involvement of APN/AdipoRs in mediating these effects opens up novel avenues for potential therapeutic interventions targeting prevalent aging eye conditions. Moreover, this review unravels the interplay between APN signaling pathways and age-related macular degeneration (AMD). The single-cell RNA-seq results validate the expression of both the receptor isoforms (AdipoR1/R2) in retinal cells. The transcriptomic analysis showed lower expression of AdipoR1/2 in dry AMD pathogenesis compared to healthy subjects. The inhibitory adiponectin peptide (APN1) demonstrated over 75% suppression of CNV, whereas the control peptide did not exert any inhibitory effect on choroidal neovascularization (CNV). The elucidation of these relationships fosters a deeper understanding of adipose tissue’s profound influence on ocular health, presenting new prospects for personalized treatments and preventative measures. Because APN1 inhibits CNV and leakage, it can be used to treat human AMD, although the possibility to treat human AMD is in the early stage and more clinical research is needed. In conclusion, this review provides a captivating journey into the enthralling world of APN, intertwining the realms of adipose biology and ophthalmology in aging. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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19 pages, 2215 KiB

Open AccessEditor’s ChoiceReview

Complement 1q/Tumor Necrosis Factor-Related Proteins (CTRPs): Structure, Receptors and Signaling

by Constanze Schanbacher, Heike M. Hermanns, Kristina Lorenz, Harald Wajant and Isabell Lang

Biomedicines 2023, 11(2), 559; https://doi.org/10.3390/biomedicines11020559 - 14 Feb 2023

Cited by 3 | Viewed by 2889

Abstract

Adiponectin and the other 15 members of the complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) family are secreted proteins composed of an N-terminal variable domain followed by a stalk region and a characteristic C-terminal trimerizing globular C1q (gC1q) domain originally identified in [...] Read more.

Adiponectin and the other 15 members of the complement 1q (C1q)/tumor necrosis factor (TNF)-related protein (CTRP) family are secreted proteins composed of an N-terminal variable domain followed by a stalk region and a characteristic C-terminal trimerizing globular C1q (gC1q) domain originally identified in the subunits of the complement protein C1q. We performed a basic PubMed literature search for articles mentioning the various CTRPs or their receptors in the abstract or title. In this narrative review, we briefly summarize the biology of CTRPs and focus then on the structure, receptors and major signaling pathways of CTRPs. Analyses of CTRP knockout mice and CTRP transgenic mice gave overwhelming evidence for the relevance of the anti-inflammatory and insulin-sensitizing effects of CTRPs in autoimmune diseases, obesity, atherosclerosis and cardiac dysfunction. CTRPs form homo- and heterotypic trimers and oligomers which can have different activities. The receptors of some CTRPs are unknown and some receptors are redundantly targeted by several CTRPs. The way in which CTRPs activate their receptors to trigger downstream signaling pathways is largely unknown. CTRPs and their receptors are considered as promising therapeutic targets but their translational usage is still hampered by the limited knowledge of CTRP redundancy and CTRP signal transduction. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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14 pages, 569 KiB

Open AccessReview

The Influence of Adipokines on Radiographic Damage in Inflammatory Rheumatic Diseases

by Eric Toussirot

Biomedicines 2023, 11(2), 536; https://doi.org/10.3390/biomedicines11020536 - 13 Feb 2023

Cited by 3 | Viewed by 2059

Abstract

Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax [...] Read more.

Inflammatory rheumatic diseases (IRDs) are complex immune-mediated diseases that are characterized by chronic inflammation of the joints. Rheumatoid arthritis (RA) and spondyloarthritis (SpA), including axial SpA (ax SpA) and psoriatic arthritis (PsA), are the most common forms of IRD. Both RA and ax SpA are characterized by a chronic course with progressive structural modifications, namely, cartilage damage and bone erosions in RA and osteoproliferative changes with spinal ossifications in ax SpA. The adipose tissue is involved in the pathophysiology of IRDs via the release of several proteins, namely, adipokines. Several adipokines with pro-inflammatory effects have been identified, such as leptin, adiponectin, visfatin and resistin. In this review, we discuss the role that adipokines may play in the structural modifications of the peripheral joints and/or axial skeleton. In RA, the role of leptin in structural damage remains controversial, while adiponectin and its high-molecular-weight isoform are known to have an influence on the development of bone erosions and radiographic progression. Resistin also appears to be a potent detrimental adipokine for the joints in RA. In ax SpA, visfatin seems to be an attractive candidate for radiographic progression, while leptin and adiponectin have negative effects on radiographic progression. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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24 pages, 1882 KiB

Open AccessReview

Extracellular Vesicles as Carriers of Adipokines and Their Role in Obesity

by Tamara Camino, Nerea Lago-Baameiro and María Pardo

Biomedicines 2023, 11(2), 422; https://doi.org/10.3390/biomedicines11020422 - 1 Feb 2023

Cited by 8 | Viewed by 3436

Abstract

Extracellular vesicles (EVs) have lately arisen as new metabolic players in energy homeostasis participating in intercellular communication at the local and distant levels. These nanosized lipid bilayer spheres, carrying bioactive molecular cargo, have somehow changed the paradigm of biomedical research not only as [...] Read more.

Extracellular vesicles (EVs) have lately arisen as new metabolic players in energy homeostasis participating in intercellular communication at the local and distant levels. These nanosized lipid bilayer spheres, carrying bioactive molecular cargo, have somehow changed the paradigm of biomedical research not only as a non-classic cell secretion mechanism, but as a rich source of biomarkers and as useful drug-delivery vehicles. Although the research about the role of EVs on metabolism and its deregulation on obesity and associated pathologies lagged slightly behind other diseases, the knowledge about their function under normal and pathological homeostasis is rapidly increasing. In this review, we are focusing on the current research regarding adipose tissue shed extracellular vesicles including their characterization, size profile, and molecular cargo content comprising miRNAs and membrane and intra-vesicular proteins. Finally, we will focus on the functional aspects attributed to vesicles secreted not only by adipocytes, but also by other cells comprising adipose tissue, describing the evidence to date on the deleterious effects of extracellular vesicles released by obese adipose tissue both locally and at the distant level by interacting with other peripheral organs and even at the central level. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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17 pages, 691 KiB

Open AccessReview

Targeting Adiponectin in Breast Cancer

by Rawan Nehme, Mona Diab-Assaf, Caroline Decombat, Laetitia Delort and Florence Caldefie-Chezet

Biomedicines 2022, 10(11), 2958; https://doi.org/10.3390/biomedicines10112958 - 17 Nov 2022

Cited by 17 | Viewed by 3242

Abstract

Obesity and breast cancer are two major health issues that could be categorized as sincere threats to human health. In the last few decades, the relationship between obesity and cancer has been well established and extensively investigated. There is strong evidence that overweight [...] Read more.

Obesity and breast cancer are two major health issues that could be categorized as sincere threats to human health. In the last few decades, the relationship between obesity and cancer has been well established and extensively investigated. There is strong evidence that overweight and obesity increase the risk of postmenopausal breast cancer, and adipokines are the central players in this relationship. Produced and secreted predominantly by white adipose tissue, adiponectin is a bioactive molecule that exhibits numerous protective effects and is considered the guardian angel of adipokine. In the obesity–cancer relationship, more and more evidence shows that adiponectin may prevent and protect individuals from developing breast cancer. Recently, several updates have been published on the implication of adiponectin in regulating tumor development, progression, and metastases. In this review, we provide an updated overview of the metabolic signaling linking adiponectin and breast cancer in all its stages. On the other hand, we critically summarize all the available promising candidates that may reactivate these pathways mainly by targeting adiponectin receptors. These molecules could be synthetic small molecules or plant-based proteins. Interestingly, the advances in genomics have made it possible to create peptide sequences that could specifically replace human adiponectin, activate its receptor, and mimic its function. Thus, the obvious anti-cancer activity of adiponectin on breast cancer should be better exploited, and adiponectin must be regarded as a serious biomarker that should be targeted in order to confront this threatening disease. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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19 pages, 1922 KiB

Open AccessReview

New Insights into Adiponectin and Leptin Roles in Chronic Kidney Disease

by Susana Coimbra, Susana Rocha, Maria João Valente, Cristina Catarino, Elsa Bronze-da-Rocha, Luís Belo and Alice Santos-Silva

Biomedicines 2022, 10(10), 2642; https://doi.org/10.3390/biomedicines10102642 - 20 Oct 2022

Cited by 16 | Viewed by 2500

Abstract

Chronic kidney disease (CKD) is commonly associated with a high burden of comorbidities and poor clinical outcomes. Malnutrition–inflammation–atherosclerosis syndrome is common in the more severe stages of CKD, suggesting a close interplay for these three comorbid conditions. Both malnutrition and obesity are associated [...] Read more.

Chronic kidney disease (CKD) is commonly associated with a high burden of comorbidities and poor clinical outcomes. Malnutrition–inflammation–atherosclerosis syndrome is common in the more severe stages of CKD, suggesting a close interplay for these three comorbid conditions. Both malnutrition and obesity are associated with a disturbed adipokine profile and inflammation, contributing to a higher risk of cardiovascular disease (CVD) events. Adiponectin and leptin have important roles in carbohydrate and lipid metabolism, and in the inflammatory process. The effects of adiponectin and leptin alterations in CKD, which are usually increased, and their association with the different comorbidities found in CKD, will be focused on to understand their crosstalk with the risk of CVD events. Nonetheless, although adiponectin and leptin contribute to a higher risk of CVD events, further studies are warranted to fully clarify their roles, especially when different comorbidities exist. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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32 pages, 1786 KiB

Open AccessEditor’s ChoiceReview

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

by Susanne Schüler-Toprak, Olaf Ortmann, Christa Buechler and Oliver Treeck

Biomedicines 2022, 10(10), 2503; https://doi.org/10.3390/biomedicines10102503 - 7 Oct 2022

Cited by 23 | Viewed by 5451

Abstract

Polycystic ovary syndrome (PCOS) and endometriosis are frequent diseases of the female reproductive tract causing high morbidity as they can significantly affect fertility and quality of life. Adipokines are pleiotropic signaling molecules secreted by white or brown adipose tissues with a central role [...] Read more.

Polycystic ovary syndrome (PCOS) and endometriosis are frequent diseases of the female reproductive tract causing high morbidity as they can significantly affect fertility and quality of life. Adipokines are pleiotropic signaling molecules secreted by white or brown adipose tissues with a central role in energy metabolism. More recently, their involvement in PCOS and endometriosis has been demonstrated. In this review article, we provide an update on the role of adipokines in both diseases and summarize previous findings. We also address the results of multi-omics approaches in adipokine research to examine the role of single nucleotide polymorphisms (SNPs) in genes coding for adipokines and their receptors, the secretome of adipocytes and to identify epigenetic alterations of adipokine genes that might be conferred from mother to child. Finally, we address novel data on the role of brown adipose tissue (BAT), which seems to have notable effects on PCOS. For this review, original research articles on adipokine actions in PCOS and endometriosis are considered, which are listed in the PubMed database. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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21 pages, 1106 KiB

Open AccessReview

Dipeptidyl Peptidase 4 (DPP4) as A Novel Adipokine: Role in Metabolism and Fat Homeostasis

by Ilaria Barchetta, Flavia Agata Cimini, Sara Dule and Maria Gisella Cavallo

Biomedicines 2022, 10(9), 2306; https://doi.org/10.3390/biomedicines10092306 - 16 Sep 2022

Cited by 19 | Viewed by 4645

Abstract

Dipeptidyl peptidase 4 (DPP4) is a molecule implicated in the regulation of metabolic homeostasis and inflammatory processes, and it exerts its main action through its enzymatic activity. DPP4 represents the enzyme most involved in the catabolism of incretin hormones; thus, its activity impacts [...] Read more.

Dipeptidyl peptidase 4 (DPP4) is a molecule implicated in the regulation of metabolic homeostasis and inflammatory processes, and it exerts its main action through its enzymatic activity. DPP4 represents the enzyme most involved in the catabolism of incretin hormones; thus, its activity impacts appetite, energy balance, and the fine regulation of glucose homeostasis. Indeed, DPP4 inhibitors represent a class of antidiabetic agents widely used for the treatment of Type 2 diabetes mellitus (T2DM). DPP4 also acts as an adipokine and is mainly secreted by the adipose tissue, mostly from mature adipocytes of the visceral compartment, where it exerts autocrine and paracrine activities. DPP4 can disrupt insulin signaling within the adipocyte and in other target cells and tissues, where it also favors the development of a proinflammatory environment. This is likely at the basis of the presence of elevated circulating DPP4 levels in several metabolic diseases. In this review, we summarize the most recent evidence of the role of the DPP4 as an adipokine-regulating glucose/insulin metabolism and fat homeostasis, with a particular focus on clinical outcomes associated with its increased secretion in the presence of adipose tissue accumulation and dysfunction. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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12 pages, 1014 KiB

Open AccessReview

Heparan Sulfate: A Regulator of White Adipocyte Differentiation and of Vascular/Adipocyte Interactions

by J. Michael Sorrell and Arnold I. Caplan

Biomedicines 2022, 10(9), 2115; https://doi.org/10.3390/biomedicines10092115 - 29 Aug 2022

Cited by 1 | Viewed by 1826

Abstract

White adipose tissues are major endocrine organs that release factors, termed adipokines, which affect other major organ systems. The development and functions of adipose tissues depend largely upon the glycosaminoglycan heparan sulfate. Heparan sulfate proteoglycans (HSPGs) surround both adipocytes and vascular structures and [...] Read more.

White adipose tissues are major endocrine organs that release factors, termed adipokines, which affect other major organ systems. The development and functions of adipose tissues depend largely upon the glycosaminoglycan heparan sulfate. Heparan sulfate proteoglycans (HSPGs) surround both adipocytes and vascular structures and facilitate the communication between these two components. This communication mediates the continued export of adipokines from adipose tissues. Heparan sulfates regulate cellular physiology and communication through a sulfation code that ionically interacts with heparan-binding regions on a select set of proteins. Many of these proteins are growth factors and chemokines that regulate tissue function and inflammation. Cells regulate heparan sulfate sulfation through the release of heparanases and sulfatases. It is now possible to tissue engineer vascularized adipose tissues that express heparan sulfate proteoglycans. This makes it possible to use these tissue constructs to study the role of heparan sulfates in the regulation of adipokine production and release. It is possible to regulate the production of heparanases and sulfatases in order to fine-tune experimental studies. Full article

(This article belongs to the Special Issue 10th Anniversary of Biomedicines—Recent Advances on Adipokines)

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