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16 pages, 1842 KiB

Open AccessArticle

A Multi-Omics Approach to Disclose Metabolic Pathways Impacting Intestinal Permeability in Obese Patients Undergoing Very Low Calorie Ketogenic Diet

by Giuseppe Celano, Francesc Maria Calabrese, Giuseppe Riezzo, Benedetta D’Attoma, Antonia Ignazzi, Martina Di Chito, Annamaria Sila, Sara De Nucci, Roberta Rinaldi, Michele Linsalata, Carmen Aurora Apa, Leonardo Mancini, Maria De Angelis, Gianluigi Giannelli, Giovanni De Pergola and Francesco Russo

Nutrients 2024, 16(13), 2079; https://doi.org/10.3390/nu16132079 (registering DOI) - 28 Jun 2024

Abstract

A very low calorie ketogenic diet (VLCKD) impacts host metabolism in people marked by an excess of visceral adiposity, and it affects the microbiota composition in terms of taxa presence and relative abundances. As a matter of fact, there is little available literature dealing with microbiota differences in obese patients marked by altered intestinal permeability. With the aim of inspecting consortium members and their related metabolic pathways, we inspected the microbial community profile, together with the set of volatile organic compounds (VOCs) from untargeted fecal and urine metabolomics, in a cohort made of obese patients, stratified based on both normal and altered intestinal permeability, before and after VLCKD administration. Based on the taxa relative abundances, we predicted microbiota-derived metabolic pathways whose variations were explained in light of our cohort symptom picture. A totally different number of statistically significant pathways marked samples with altered permeability, reflecting an important shift in microbiota taxa. A combined analysis of taxa, metabolic pathways, and metabolomic compounds delineates a set of markers that is useful in describing obesity dysfunctions and comorbidities. Full article

(This article belongs to the Section Nutrition and Obesity)

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18 pages, 5314 KiB

Open AccessArticle

Regulatory Effects of 198-bp Structural Variants in the GSTA2 Promoter Region on Adipogenesis in Chickens

by Wangyu Li, Meng Xu, Zihao Zhang, Jiaying Liang, Rong Fu, Wujian Lin, Wen Luo, Xiquan Zhang and Tuanhui Ren

Int. J. Mol. Sci. 2024, 25(13), 7155; https://doi.org/10.3390/ijms25137155 (registering DOI) - 28 Jun 2024

Abstract

Molecular breeding accelerates animal breeding and improves efficiency by utilizing genetic mutations. Structural variations (SVs), a significant source of genetic mutations, have a greater impact on phenotypic variation than SNPs. Understanding SV functional mechanisms and obtaining precise information are crucial for molecular breeding. In this study, association analysis revealed significant correlations between 198-bp SVs in the GSTA2 promoter region and abdominal fat weight, intramuscular fat content, and subcutaneous fat thickness in chickens. High expression of GSTA2 in adipose tissue was positively correlated with the abdominal fat percentage, and different genotypes of GSTA2 exhibited varied expression patterns in the liver. The 198-bp SVs regulate GSTA2 expression by binding to different transcription factors. Overexpression of GSTA2 promoted preadipocyte proliferation and differentiation, while interference had the opposite effect. Mechanistically, the 198-bp fragment contains binding sites for transcription factors such as C/EBPα that regulate GSTA2 expression and fat synthesis. These SVs are significantly associated with chicken fat traits, positively influencing preadipocyte development by regulating cell proliferation and differentiation. Our work provides compelling evidence for the use of 198-bp SVs in the GSTA2 promoter region as molecular markers for poultry breeding and offers new insights into the pivotal role of the GSTA2 gene in fat generation. Full article

(This article belongs to the Section Molecular Genetics and Genomics)

13 pages, 666 KiB

Open AccessArticle

Pilot Study for Isolation of Stromal Vascular Fraction with Collagenase Using an Automated Processing System

by Gershon Zinger, Yoav Gronovich, Adi Maisel Lotan and Racheli Sharon-Gabbay

Int. J. Mol. Sci. 2024, 25(13), 7148; https://doi.org/10.3390/ijms25137148 (registering DOI) - 28 Jun 2024

Viewed by 52

Abstract

There are many potential therapeutic applications for autologous adipose-derived stromal cells. These cells are found in a heterogeneous population isolated from adipose tissue called the stromal vascular fraction (SVF). Closed automated systems are available to release cells from the adherent stroma. Here, we test one system to evaluate the heterogeneous output for yield, purity, cellular characterization, and stemness criteria. The SVF was isolated from three donors using the Automated Cell Station (ACS) from BSL Co., Ltd., Busan, Republic of Korea. The SVF cellular output was characterized for cell yield and viability, immunophenotyping analysis, pluripotent differentiation potential, adhesion to plastic, and colony-forming units. Additionally, the SVF was tested for endotoxin and collagenase residuals. The SVF yield from the ACS system was an average volume of 7.9 ± 0.5 mL containing an average of 19 × 10⁶ nucleated cells with 85 ± 12% viability. Flow cytometry identified a variety of cells, including ASCs (23%), macrophages (24%), endothelial cells (5%), pericytes (4%), and transitional cells (0.5%). The final concentrated product contained cells capable of differentiating into adipogenic, chondrogenic, and osteogenic phenotypes. Furthermore, tests for SVF sterility and purity showed no evidence of endotoxin or collagenase residuals. The ACS system can efficiently process cells from adipose tissue within the timeframe of a single surgical procedure. The cellular characterization indicated that this system can yield a sterile and concentrated SVF output, providing a valuable source of ASCs within the heterogeneous cell population. Full article

(This article belongs to the Topic Pluripotent Stem Cells)

14 pages, 3400 KiB

Open AccessArticle

Euiin-Tang Attenuates Obesity-Induced Asthma by Resolving Metaflammation

by Ye-Eul Lee and Dong-Soon Im

Pharmaceuticals 2024, 17(7), 853; https://doi.org/10.3390/ph17070853 (registering DOI) - 28 Jun 2024

Viewed by 96

Abstract

Euiin-tang reduces obesity and hypertension. Patients with obesity may develop obesity-induced asthma (OIA) owing to phlegm dampness. This study aimed to determine whether euiin-tang alleviates high-fat diet (HFD)-induced OIA in C57BL/6 mice. OIA was developed by HFD feeding for 15 weeks in C57BL/6 mice, and euiin-tang (5 mg/10 g/day) was orally administered for the last five weeks. Oral administration of euiin-tang suppressed HFD-induced changes in body weight, liver weight, airway hypersensitivity (AHR), and immune cell infiltration in bronchoalveolar lavage fluid. Histological analysis revealed that euiin-tang treatment suppressed HFD-induced mucosal inflammation, hypersecretion, and fibrosis. The lungs and gonadal white adipose tissue showed increased expression of inflammatory cytokines (IL-1β, IL-17A, TNF-α, IL-6, IL-13, IFN-γ, MPO, and CCL2) following HFD, whereas euiin-tang inhibited this increase. HFD also increased the number of pro-inflammatory CD86⁺ M1 macrophages and decreased the number of anti-inflammatory CD206⁺ M2 macrophages in the lungs, whereas euiin-tang treatment reversed these effects. HFD induced a decrease in adiponectin and an increase in leptin, which was reversed by euiin-tang. Therefore, euiin-tang may be a potential therapeutic agent for OIA because it suppresses metaflammation as demonstrated in the present study. Full article

(This article belongs to the Special Issue The Mode of Action of Herbal Medicines and Natural Products)

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16 pages, 3539 KiB

Open AccessArticle

Formulation Effects on the Mechano-Physical Properties of In Situ-Forming Resilient Hydrogels for Breast Tissue Regeneration

by Daniella Goder Orbach and Meital Zilberman

J. Funct. Biomater. 2024, 15(7), 176; https://doi.org/10.3390/jfb15070176 - 28 Jun 2024

Viewed by 111

Abstract

The need for a long-term solution for filling the defects created during partial mastectomies due to breast cancer diagnosis has not been met to date. All available defect-filling methods are non-permanent and necessitate repeat procedures. Here, we report on novel injectable porous hydrogel structures based on the natural polymers gelatin and alginate, which are designed to serve for breast reconstruction and regeneration following partial mastectomy. The effects of the formulation parameters on the mechanical and physical properties were thoroughly studied. The modulus in compression and tension were in the range of native breast tissue. Both increased with the increase in the crosslinker concentration and the polymer–air ratio. Resilience was very high, above 93% for most studied formulations, allowing the scaffold to be continuously deformed without changing its shape. The combination of high resilience and low elastic modulus is favored for adipose tissue regeneration. The physical properties of gelation time and water uptake are controllable and are affected mainly by the alginate and N-(3-dimethylaminopropyl)-N’-ethylcarbodiimide hydrochloride (EDC) concentrations and less by the polymer–air ratio. In vitro cell viability tests were performed on mouse preadipocytes and indicated high biocompatibility. The minimally invasive nature of this approach, along with the excellent properties of the scaffold, will enable the filling of complex voids while simultaneously decreasing surgical costs and greatly improving patient well-being. Full article

(This article belongs to the Special Issue Functional Hydrogels for Tissue Engineering and Regenerative Medicine)

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11 pages, 1142 KiB

Open AccessArticle

Factors Influencing Abdominal Compliance during CO₂ Insufflation in Patients Undergoing Laparoscopic Abdominal Surgery

by Ezgi Yıldırım, K. Sanem Cakar Turhan, Aysegul Güven, Derya Gökmen and Menekse Özcelik

Reports 2024, 7(3), 52; https://doi.org/10.3390/reports7030052 - 28 Jun 2024

Viewed by 106

Abstract

The aim of this study was to investigate the effect of patient demographic and anatomical characteristics on abdominal compliance (AC), which represents the slope of the pressure–volume (P–V) curve of the abdominal cavity and is a measure of the ease of abdominal dilatation. The study included 90 patients undergoing laparoscopic abdominal surgery. Subcutaneous adipose tissue and abdominal muscle thickness were measured using ultrasonography. The mean AC was calculated during insufflation using the formula (ΔV/ΔP). The relationship between demographic and anatomical variables and AC was investigated. The results demonstrated that AC was higher in men, the elderly, and women with a history of pregnancy, and lower in patients with a history of abdominal surgery. No significant correlation was found between AC and BMI, abdominal muscle thickness, and subcutaneous adipose tissue thickness. These findings suggest that morbid obesity, a common comorbidity in laparoscopic surgery, and well-developed abdominal muscles are not indicators of low AC. However, gender, age, pregnancy history, and previous abdominal surgery affect AC during laparoscopic surgery. By taking these factors into account during preoperative evaluation, it may be possible to predict patients with low AC, which could improve perioperative outcomes through the application of individualized intra-abdominal pressure (IAP) during pneumoperitoneum. Full article

(This article belongs to the Section Surgery)

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3 pages, 199 KiB

Open AccessComment

Comment on Lai et al. Dipeptidyl Peptidase 4 Stimulation Induces Adipogenesis-Related Gene Expression of Adipose Stromal Cells. Int. J. Mol. Sci. 2023, 24, 16101

by Oscar J. Cordero, Martin Kotrulev and Iria Gomez-Touriño

Int. J. Mol. Sci. 2024, 25(13), 7093; https://doi.org/10.3390/ijms25137093 - 28 Jun 2024

Viewed by 71

Abstract

Adiponectin is a circulating hormone secreted by adipose tissue that exerts, unlike other adipokines such as leptin, anti-inflammatory, anti-atherosclerotic and other protective effects on health. Adiponectin receptor agonists are being tested in clinical trials and are expected to show benefits in many diseases. In a recent article, LW Chen’s group used monocyte chemoattractant protein-1 (MCP-1/CCL2) to improve plasma levels of adiponectin, suggesting the involvement of dipeptidyl peptidase 4 (DPP4/CD26) in the mechanism. Here, we discuss the significance of the role of DPP4, favoring the increase in DPP4-positive interstitial progenitor cells, a finding that fits with the greater stemness and persistence of other DPP4/CD26-positive cells. Full article

(This article belongs to the Special Issue Obesity and Obesity Related Disorders)

20 pages, 1198 KiB

Open AccessReview

Metabolic Effects of Ketogenic Diets: Exploring Whole-Body Metabolism in Connection with Adipose Tissue and Other Metabolic Organs

by Yusra Ahmad, Dong Soo Seo and Younghoon Jang

Int. J. Mol. Sci. 2024, 25(13), 7076; https://doi.org/10.3390/ijms25137076 - 27 Jun 2024

Viewed by 204

Abstract

The ketogenic diet (KD) is characterized by minimal carbohydrate, moderate protein, and high fat intake, leading to ketosis. It is recognized for its efficiency in weight loss, metabolic health improvement, and various therapeutic interventions. The KD enhances glucose and lipid metabolism, reducing triglycerides and total cholesterol while increasing high-density lipoprotein levels and alleviating dyslipidemia. It significantly influences adipose tissue hormones, key contributors to systemic metabolism. Brown adipose tissue, essential for thermogenesis and lipid combustion, encounters modified UCP1 levels due to dietary factors, including the KD. UCP1 generates heat by uncoupling electron transport during ATP synthesis. Browning of the white adipose tissue elevates UCP1 levels in both white and brown adipose tissues, a phenomenon encouraged by the KD. Ketone oxidation depletes intermediates in the Krebs cycle, requiring anaplerotic substances, including glucose, glycogen, or amino acids, for metabolic efficiency. Methylation is essential in adipogenesis and the body’s dietary responses, with DNA methylation of several genes linked to weight loss and ketosis. The KD stimulates FGF21, influencing metabolic stability via the UCP1 pathways. The KD induces a reduction in muscle mass, potentially involving anti-lipolytic effects and attenuating proteolysis in skeletal muscles. Additionally, the KD contributes to neuroprotection, possesses anti-inflammatory properties, and alters epigenetics. This review encapsulates the metabolic effects and signaling induced by the KD in adipose tissue and major metabolic organs. Full article

(This article belongs to the Special Issue Molecular and Cellular Research on Adipose Tissue Development and Functions)

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27 pages, 2360 KiB

Open AccessSystematic Review

Mesenchymal Stromal Cells for the Enhancement of Surgical Flexor Tendon Repair in Animal Models: A Systematic Review and Meta-Analysis

by Ilias Ektor Epanomeritakis, Andreas Eleftheriou, Anna Economou, Victor Lu and Wasim Khan

Bioengineering 2024, 11(7), 656; https://doi.org/10.3390/bioengineering11070656 - 27 Jun 2024

Viewed by 324

Abstract

Flexor tendon lacerations are primarily treated by surgical repair. Limited intrinsic healing ability means the repair site can remain weak. Furthermore, adhesion formation may reduce range of motion post-operatively. Mesenchymal stromal cells (MSCs) have been trialled for repair and regeneration of multiple musculoskeletal structures. Our goal was to determine the efficacy of MSCs in enhancing the biomechanical properties of surgically repaired flexor tendons. A PRISMA systematic review was conducted using four databases (PubMed, Ovid, Web of Science, and CINAHL) to identify studies using MSCs to augment surgical repair of flexor tendon injuries in animals compared to surgical repair alone. Nine studies were included, which investigated either bone marrow- or adipose-derived MSCs. Results of biomechanical testing were extracted and meta-analyses were performed regarding the maximum load, friction and properties relating to viscoelastic behaviour. There was no significant difference in maximum load at final follow-up. However, friction, a surrogate measure of adhesions, was significantly reduced following the application of MSCs (p = 0.04). Other properties showed variable results and dissipation of the therapeutic benefits of MSCs over time. In conclusion, MSCs reduce adhesion formation following tendon injury. This may result from their immunomodulatory function, dampening the inflammatory response. However, this may come at the cost of favourable healing which will restore the tendon’s viscoelastic properties. The short duration of some improvements may reflect MSCs’ limited survival or poor retention. Further investigation is needed to clarify the effect of MSC therapy and optimise its duration of action. Full article

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11 pages, 2402 KiB

Open AccessArticle

Optimizing Choice of Skin Surrogates for Surface-Guided Stereotactic Body Radiotherapy of Lung Lesions Using Four-Dimensional Computed Tomography

by Vanda Leipold, Ivana Alerić, Mihaela Mlinarić, Domagoj Kosmina, Fran Stanić, Mladen Kasabašić, Damir Štimac, Hrvoje Kaučić, Giovanni Ursi, Karla Schwarz, Igor Nikolić, Denis Klapan and Dragan Schwarz

Cancers 2024, 16(13), 2358; https://doi.org/10.3390/cancers16132358 - 27 Jun 2024

Viewed by 226

Abstract

Image-guided radiotherapy supported by surface guidance can help to track lower lung lesions’ respiratory motion while reducing a patient’s exposure to ionizing radiation. However, it is not always clear how the skin’s respiratory motion magnitude and its correlation with the lung lesion’s respiratory motion vary between different skin regions of interest (ROI). Four-dimensional computed tomography (4DCT) images provide information on both the skin and lung respiratory motion and are routinely acquired for the purpose of treatment planning in our institution. An analysis of 4DCT images for 57 patients treated in our institution has been conducted to provide information on the respiratory motion magnitudes of nine skin ROIs of the torso, a tracking structure (TS) representing a lower lung lobe lesion, as well as the respiratory motion correlations between the nine ROIs and the TS. The effects of gender and the adipose tissue volume and distribution on these correlations and magnitudes have been analyzed. Significant differences between the ROIs in both the respiratory motion magnitudes and their correlations with the TS have been detected. An overall negative correlation between the ROI respiratory magnitudes and the adipose tissue has been detected for ROIs with rib cage support. A weak to moderate negative correlation between the adipose tissue volume and ROI-to-TS respiratory correlations has been detected for upper thorax ROIs. The respiratory magnitudes in regions without rib support tend to be larger for men than for women, but no differences in the ROI-to-TS correlation between sexes have been detected. The described findings should be considered when choosing skin surrogates for lower lung lesion motion management. Full article

(This article belongs to the Special Issue Advancements in Image-Guided Radiotherapy for the Treatment of Lung Cancer)

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18 pages, 337 KiB

Open AccessReview

Association of DNA Methylation with Infant Birth Weight in Women with Gestational Diabetes

by Renata Saucedo, Aldo Ferreira-Hermosillo, Magalhi Robledo-Clemente, Mary Flor Díaz-Velázquez and Jorge Valencia-Ortega

Metabolites 2024, 14(7), 361; https://doi.org/10.3390/metabo14070361 - 27 Jun 2024

Viewed by 188

Abstract

Offspring exposed to gestational diabetes mellitus (GDM) exhibit greater adiposity at birth. This early-life phenotype may increase offspring risk of developing obesity, metabolic syndrome, type 2 diabetes, and cardiovascular disease later in life. Infants born to women with GDM have a dysregulation of several hormones, cytokines, and growth factors related to fetal fat mass growth. One of the molecular mechanisms of GDM influencing these factors is epigenetic alterations, such as DNA methylation (DNAm). This review will examine the role of DNAm as a potential biomarker for monitoring fetal growth during pregnancy in women with GDM. This information is relevant since it may provide useful new biomarkers for the diagnosis, prognosis, and treatment of fetal growth and its later-life health consequences. Full article

(This article belongs to the Special Issue Adipose Tissue, Reproduction and Metabolic Health in Women)

12 pages, 7856 KiB

Open AccessArticle

The Liver Circadian Metabolic Homeostasis Influence by Combining Ketogenic Diet with Exercise

by Wenbo Xu, Zishi Wang, Cuican Zhang, Wenju Yang, Linchao Fan and Hong Sun

Nutrients 2024, 16(13), 2039; https://doi.org/10.3390/nu16132039 - 27 Jun 2024

Viewed by 232

Abstract

The ketogenic diet (KD) and regular exercise (EX) are both capable of orchestrating circadian metabolism homeostasis during losing weight. However, the combined effects of these two factors on circadian metabolism remain poorly understood. To determine if the combined treatment yields a superimposed physiological phenotype, we measured weight loss, white adipose, the respiratory exchange ratio (RER), heat production, and activity parameters in individual and combined treatment groups. Surprisingly, none of these metrics displayed a cumulative effect when administered in the combined treatment approach. Additionally, we investigated the impact of combination therapy on molecular homeostasis through using high-throughput liver transcriptomic approaches. The results revealed that individual and combined treatments can reprogram the circadian rhythm; yet, the combined group exhibited a minimum quantity of cyclic transcript genes. Noteworthy, the amplitude of 24 h circadian expression genes was not significantly increased in the combination treatment, indicating that the combined approach has non-overlapping effects on maintenance peripheral metabolism homeostasis. This may be due to the liver requiring less ketogenic and gluconeogenic potential during metabolic processes. This research suggests that combined treatment may have adverse effects on the body’s homeostasis and provide crucial insights for the homeostatic health of athletes or individuals who wish to lose weight. Full article

(This article belongs to the Special Issue Adipose Tissue Metabolism and Exercise in Health and Disease)

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15 pages, 2428 KiB

Open AccessArticle

Effects of the MCF-7 Exhausted Medium on hADSC Behaviour

by Giuseppe Garroni, Sara Cruciani, Diletta Serra, Renzo Pala, Donatella Coradduzza, Maria Laura Cossu, Giorgio Carlo Ginesu, Carlo Ventura and Margherita Maioli

Int. J. Mol. Sci. 2024, 25(13), 7026; https://doi.org/10.3390/ijms25137026 - 27 Jun 2024

Viewed by 148

Abstract

Stem cells possess the ability to differentiate into different lineages and the ability to self-renew, thus representing an excellent tool for regenerative medicine. They can be isolated from different tissues, including the adipose tissue. Adipose tissue and human adipose-derived stem cells (hADSCs) are privileged candidates for regenerative medicine procedures or other plastic reconstructive surgeries. The cellular environment is able to influence the fate of stem cells residing in the tissue. In a previous study, we exposed hADSCs to an exhausted medium of a breast cancer cell line (MCF-7) recovered at different days (4, 7, and 10 days). In the same paper, we inferred that the medium was able to influence the behaviour of stem cells. Considering these results, in the present study, we evaluated the expression of the major genes related to adipogenic and osteogenic differentiation. To confirm the gene expression data, oil red and alizarin red colorimetric assays were performed. Lastly, we evaluated the expression of miRNAs influencing the differentiation process and the proliferation rate, maintaining a proliferative state. The data obtained confirmed that cells exposed to the medium maintained a stem and proliferative state that could lead to a risky proliferative phenotype. Full article

(This article belongs to the Section Molecular Biology)

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13 pages, 1924 KiB

Open AccessArticle

Ghrelin Expression in Atherosclerotic Plaques and Perivascular Adipose Tissue: Implications for Vascular Inflammation in Peripheral Artery Disease

by Sorin Nicolae Peiu, Diana Gabriela Iosep, Mihai Danciu, Veronica Scripcaru, Victor Ianole and Veronica Mocanu

J. Clin. Med. 2024, 13(13), 3737; https://doi.org/10.3390/jcm13133737 - 26 Jun 2024

Viewed by 225

Abstract

Atherosclerosis, a leading cause of peripheral artery disease (PAD), is driven by lipid accumulation and chronic inflammation within arterial walls. Objectives: This study investigates the expression of ghrelin, an anti-inflammatory peptide hormone, in plaque morphology and inflammation in patients with PAD, highlighting its potential role in age-related vascular diseases and metabolic syndrome. Methods: The analysis specifically focused on the immunohistochemical expression of ghrelin in atherosclerotic plaques and perivascular adipose tissue (PVAT) from 28 PAD patients. Detailed immunohistochemical staining was performed to identify ghrelin within these tissues, comparing its presence in various plaque types and assessing its association with markers of inflammation and macrophage polarization. Results: Significant results showed a higher prevalence of calcification in fibro-lipid plaques (63.1%) compared to fibrous plaques, with a notable difference in inflammatory infiltration between the two plaque types (p = 0.027). Complicated plaques exhibited increased ghrelin expression, suggesting a modulatory effect on inflammatory processes, although this did not reach statistical significance. The correlation between ghrelin levels and macrophage presence, especially the pro-inflammatory M1 phenotype, indicates ghrelin’s involvement in the inflammatory dynamics of atherosclerosis. Conclusions: The findings propose that ghrelin may influence plaque stability and vascular inflammation, pointing to its therapeutic potential in managing atherosclerosis. The study underlines the necessity for further research to clarify ghrelin’s impact on vascular health, particularly in the context of metabolic syndrome and age-related vascular alterations. Full article

(This article belongs to the Special Issue Latest Research in Peripheral Artery Diseases)

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Abstract

Background: Though maternal diabetes effects are well described in the literature, the effects of maternal diabetes in postnatal phases are often overlooked. Diabetic individuals have higher levels of circulating glycotoxins, and there is a positive correlation between maternal-derived glycotoxins and circulating glycotoxins in their progeny. Previous studies evaluated the metabolic effects of high glycotoxin exposure during lactation in adult animals. However, here we focus on the cardiovascular system of juvenile rats. Methods: For this, we used two experimental models: 1. High Methylglyoxal (MG) environment: pregnant Wistar rats were injected with PBS (VEH group) or Methylglyoxal (MG group; 60 mg/kg/day; orally, postnatal day (PND) 3 to PND14). 2. GLO-1 inhibition: pregnant Wistar rats were injected with dimethyl sulfoxide (VEH group) or a GLO-1 inhibitor (BBGC group; 5 mg/kg/day; subcutaneously, PND1–PND5). The offspring were evaluated at PND45. Results: MG offspring presented cardiac dysfunction and subtly worsened vasomotor responses in the presence of perivascular adipose tissue, without morphological alterations. In addition, an endogenous increase in maternal glycotoxins impacts offspring vasomotricity due to impaired redox status. Conclusions: Our data suggest that early glycotoxin exposure led to cardiac and vascular impairments, which may increase the risk for developing cardiovascular diseases later in life. Full article

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