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Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis
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Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis

A special issue of Life (ISSN 2075-1729). This special issue belongs to the section "Physiology and Pathology".

Deadline for manuscript submissions: closed (31 August 2023) | Viewed by 19772

Special Issue Editor

Dr. Dimiter Avtanski

E-Mail Website
Guest Editor
Friedman Diabetes Institute at Lenox Hill Hospital, Northwell Health, Lenox Hill Hospital, New York, NY, USA
Interests: obesity; cytokine; diabetes; breast cancer; steroid
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Today, obesity is officially labeled as a pandemic comprising more than 650 million people globally. In addition, almost 2 billion of the world population are overweight. Obesity has become a significant threat killing more people than undernourishment. The future is also not very promising – 39 million of today’s children under the age of 5 are either overweight or obese.

Adipose is active secretory tissue that produces numerous peptides, steroids, and lipids, among other substances. Obesity leads to an increase in macrophage infiltration and disturbed adipocyte maturation, which results in chronic inflammation. Dysregulated cytokine levels establish a positive feedback loop, further amplifying the inflammation process and oxidative stress, thus inducing insulin resistance, hyperinsulinemia, and diabetes. High levels of insulin, insulin-like growth factors (IGFs), proinflammatory cytokines, and estrogens can also promote cancer development. The endocrine function of the adipose tissue is closely linked to the reproductive system as well, as either obesity or low weight may cause infertility.

This special issue aims to combine discoveries in endocrinology, immunology, oncology, reproductive biology, and other disciplines. Prospective authors are encouraged to submit research or review manuscripts on obesity, diabetes, steroid hormone metabolism, and cancer initiation and progression.

Dr. Dimiter Avtanski
Guest Editor

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Keywords

  • obesity
  • cytokine
  • diabetes
  • T2DM
  • breast cancer
  • steroid
  • estrogen

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Published Papers (7 papers)

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Research

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12 pages, 1413 KiB  
Article
L-Arginine-Dependent Nitric Oxide Production in the Blood of Patients with Type 2 Diabetes: A Pilot, Five-Year Prospective Study
by Irina Stoian, Liviu Iosif, Marilena Gilca, Adelina Vlad, Ioan Tivig, Ovidiu Marius Bradescu and Octavian Savu
Life 2024, 14(5), 556; https://doi.org/10.3390/life14050556 - 26 Apr 2024
Viewed by 1213
Abstract
Backgound: Type 2 diabetes mellitus (T2DM) is a major cardiovascular risk factor. Nitric oxide (NO) is one of the many molecules that regulate vascular tone, and red blood cells (RBCs) are known to play an important role in adjusting cardiac function through [...] Read more.
Backgound: Type 2 diabetes mellitus (T2DM) is a major cardiovascular risk factor. Nitric oxide (NO) is one of the many molecules that regulate vascular tone, and red blood cells (RBCs) are known to play an important role in adjusting cardiac function through NO export from RBCs. Our study prospectively investigated the L-arginine (L-arg)–nitric oxide (NO) metabolic pathway in the erythrocytes and plasma of subjects with T2DM. Methods: RBCs and plasma were collected from patients with T2DM (n = 10), at first clinical onset (baseline) and after five years of disease evolution (follow-up). L-arg content was assayed by competitive enzyme-linked immunoassay. Arginase activity and nitrate/nitrite levels were measured using spectrophotometry. Results: When compared to baseline, L-arg content decreased in RBCs and remained similar in the plasma; NO production decreased in RBCs and the plasma; and arginase activity was lower in RBCs and increased in plasma. Conclusions: The L-arg/NO metabolic pathway decreases in the RBCs of patients with T2DM five years after the first clinical onset. The persistent decrease in RBCs’ arginase activity fails to compensate for the sustained decrease in RBCs’ NO production in the diabetic environment. This pilot study indicates that the NO-RBC pool is depleted during the progression of the disease in the same cohort of T2DM patients. Full article
(This article belongs to the Special Issue Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis)
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15 pages, 6728 KiB  
Article
Influence of Body Mass Index and Duration of Disease on Chromosome Damage in Lymphocytes of Patients with Diabetes
by Laura Šiaulienė, Jūratė Kazlauskaitė, Dalia Jurkėnaitė, Žydrūnė Visockienė and Juozas R. Lazutka
Life 2023, 13(9), 1926; https://doi.org/10.3390/life13091926 - 16 Sep 2023
Viewed by 1395
Abstract
It is well-established that patients with diabetes mellitus (DM) have a higher incidence of several types of cancer. The precise mechanisms of this association are still unknown, but obesity and chronic inflammation-induced reactive oxygen species (ROS) are thought to be the main risk [...] Read more.
It is well-established that patients with diabetes mellitus (DM) have a higher incidence of several types of cancer. The precise mechanisms of this association are still unknown, but obesity and chronic inflammation-induced reactive oxygen species (ROS) are thought to be the main risk factors. ROS may produce different DNA damage, which could eventually lead to cancer. The main objective of this study was to evaluate the relation of chromosome aberrations (CA) with disease status, demographics, and clinical parameters in 33 subjects with type 1 DM (T1DM), 22 subjects with type 2 DM (T2DM), and 21 controls. CAs were analyzed in cultured peripheral blood lymphocytes and subdivided into chromatid (CTA)- and chromosome (CSA)-type aberrations. Compared with controls, higher levels of CTAs and CSAs were observed in T1DM (p = 0.0053 and p = 0.0203, respectively) and T2DM (p = 0.0133 and p = 0.00002, respectively). While there was no difference in CTAs between T1DM and T2DM, CSAs were higher in T2DM (p = 0.0173). A significant positive association between CTAs and disease duration (rs = 0.2938, p = 0.0099) and between CSAs and disease duration (rs = 0.4306, p = 0.0001), age (rs = 0.3932, p = 0.0004), and body mass index (BMI) (rs = 0.3502, p = 0.0019) was revealed. After multiple regression analysis, duration of disease remained significant for CTA, CSA, and CAs (p = 0.0042, p = 0.00003, and p = 0.00002, respectively). For CSA, BMI and the use of statins were the other important confounding variables (p = 0.0105 and p = 0.0763). Thus, this study demonstrated that both T1DM and T2DM patients had a higher number of all types of aberrations than controls, which increases with the prolonged disease duration. Higher BMI was associated with a higher frequency of CSA. The use of statins might be beneficial for reducing chromosome damage, but further investigations are needed to confirm this association. Full article
(This article belongs to the Special Issue Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis)
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26 pages, 6425 KiB  
Article
Hypercoagulability State Combined with Post-Treatment Hypofibrinolysis in Invasive Breast Cancer: A Seven-Year Follow-Up Evaluating Disease-Free and Overall Survival
by Katarzyna Wrzeszcz, Piotr Rhone, Katarzyna Kwiatkowska and Barbara Ruszkowska-Ciastek
Life 2023, 13(5), 1106; https://doi.org/10.3390/life13051106 - 28 Apr 2023
Cited by 2 | Viewed by 2335
Abstract
(1) Background: Cancer treatment, including chemotherapy, endocrine therapy, targeted therapy and radiotherapy, has been identified as an important independent risk factor for venous thromboembolism in cancer patients. The aim of the study was to evaluate the effect of adjuvant therapy on the coagulation [...] Read more.
(1) Background: Cancer treatment, including chemotherapy, endocrine therapy, targeted therapy and radiotherapy, has been identified as an important independent risk factor for venous thromboembolism in cancer patients. The aim of the study was to evaluate the effect of adjuvant therapy on the coagulation and fibrinolysis components in invasive breast cancer. (2) Methods: Tissue factor pathway inhibitor (TFPI), tissue factor (TF), tissue plasminogen activator (t-PA), plasminogen activator inhibitor-1 (PAI-1) antigen (concentration) and TFPI and TF activities were examined in the blood samples of 60 breast cancer patients treated by adjuvant chemotherapy, endocrine therapy, radiotherapy and immunotherapy. Blood samples were taken 24 h before primary surgery and 8 months after tumour removal surgery. (3) Results: Adjuvant therapy administrated to breast cancer patients significantly increased the concentration of plasma TF, the PAI-1 antigen and also the activity of TFPI and TF, but significantly decreased the level of the t-PA antigen. Combined chemotherapy and endocrine therapy, but not monotherapy, has an important effect on haemostatic biomarker levels. (4) Conclusions: Breast cancer patients receiving adjuvant therapy have an elevated risk of developing a hypercoagulability and hypofibrinolysis state leading to venous thromboembolism. Full article
(This article belongs to the Special Issue Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis)
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Review

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20 pages, 2464 KiB  
Review
Cardiovascular Effects of Weight Loss in Obese Patients with Diabetes: Is Bariatric Surgery the Additional Arrow in the Quiver?
by Roberta Bottino, Andreina Carbone, Tiziana Formisano, Saverio D’Elia, Massimiliano Orlandi, Simona Sperlongano, Daniele Molinari, Pasquale Castaldo, Alberto Palladino, Consiglia Barbareschi, Salvatore Tolone, Ludovico Docimo and Giovanni Cimmino
Life 2023, 13(7), 1552; https://doi.org/10.3390/life13071552 - 13 Jul 2023
Cited by 3 | Viewed by 2043
Abstract
Obesity is an increasingly widespread disease worldwide because of lifestyle changes. It is associated with an increased risk of cardiovascular disease, primarily type 2 diabetes mellitus, with an increase in major cardiovascular adverse events. Bariatric surgery has been shown to be able to [...] Read more.
Obesity is an increasingly widespread disease worldwide because of lifestyle changes. It is associated with an increased risk of cardiovascular disease, primarily type 2 diabetes mellitus, with an increase in major cardiovascular adverse events. Bariatric surgery has been shown to be able to reduce the incidence of obesity-related cardiovascular disease and thus overall mortality. This result has been shown to be the result of hormonal and metabolic effects induced by post-surgical anatomical changes, with important effects on multiple hormonal and molecular axes that make this treatment more effective than conservative therapy in determining a marked improvement in the patient’s cardiovascular risk profile. This review, therefore, aimed to examine the surgical techniques currently available and how these might be responsible not only for weight loss but also for metabolic improvement and cardiovascular benefits in patients undergoing such procedures. Full article
(This article belongs to the Special Issue Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis)
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22 pages, 2082 KiB  
Review
Possible Mechanisms Linking Obesity, Steroidogenesis, and Skeletal Muscle Dysfunction
by Anna F. Sheptulina, Karina Yu Antyukh, Anton R. Kiselev, Natalia P. Mitkovskaya and Oxana M. Drapkina
Life 2023, 13(6), 1415; https://doi.org/10.3390/life13061415 - 19 Jun 2023
Cited by 2 | Viewed by 4629
Abstract
Increasing evidence suggests that skeletal muscles may play a role in the pathogenesis of obesity and associated conditions due to their impact on insulin resistance and systemic inflammation. Skeletal muscles, as well as adipose tissue, are largely recognized as endocrine organs, producing biologically [...] Read more.
Increasing evidence suggests that skeletal muscles may play a role in the pathogenesis of obesity and associated conditions due to their impact on insulin resistance and systemic inflammation. Skeletal muscles, as well as adipose tissue, are largely recognized as endocrine organs, producing biologically active substances, such as myokines and adipokines. They may have either beneficial or harmful effects on the organism and its functions, acting through the endocrine, paracrine, and autocrine pathways. Moreover, the collocation of adipose tissue and skeletal muscles, i.e., the amount of intramuscular, intermuscular, and visceral adipose depots, may be of major importance for metabolic health. Traditionally, the generalized and progressive loss of skeletal muscle mass and strength or physical function, named sarcopenia, has been thought to be associated with age. That is why most recently published papers are focused on the investigation of the effect of obesity on skeletal muscle function in older adults. However, accumulated data indicate that sarcopenia may arise in individuals with obesity at any age, so it seems important to clarify the possible mechanisms linking obesity and skeletal muscle dysfunction regardless of age. Since steroids, namely, glucocorticoids (GCs) and sex steroids, have a major impact on the amount and function of both adipose tissue and skeletal muscles, and are involved in the pathogenesis of obesity, in this review, we will also discuss the role of steroids in the interaction of these two metabolically active tissues in the course of obesity. Full article
(This article belongs to the Special Issue Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis)
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13 pages, 1051 KiB  
Review
Obesity and Clonal Hematopoiesis of Indeterminate Potential: Allies in Cardiovascular Diseases and Malignancies
by Luka Komic, Marko Kumric, Hrvoje Urlic, Azer Rizikalo, Marko Grahovac, Jelena Kelam, Marion Tomicic, Doris Rusic, Tina Ticinovic Kurir and Josko Bozic
Life 2023, 13(6), 1365; https://doi.org/10.3390/life13061365 - 10 Jun 2023
Cited by 2 | Viewed by 2152
Abstract
The clonal hematopoiesis of indeterminate potential (CHIP) is a term used to describe individuals who have detectable somatic mutations in genes commonly found in individuals with hematologic cancers but without any apparent evidence of such conditions. The mortality rate in individuals with CHIP [...] Read more.
The clonal hematopoiesis of indeterminate potential (CHIP) is a term used to describe individuals who have detectable somatic mutations in genes commonly found in individuals with hematologic cancers but without any apparent evidence of such conditions. The mortality rate in individuals with CHIP is remarkably higher than the influence ascribed to hematologic malignancies, and it is plausible that cardiovascular diseases (CVD) could elucidate the apparent disparity. Studies have shown that the most frequently altered genes in CHIP are associated with the increased incidence of CVDs, type 2 diabetes mellitus (T2DM) and myeloid malignancies, as well as obesity. Additionally, multiple research studies have confirmed that obesity is also independently associated with these conditions, particularly the development and progression of atherosclerotic CVD. Considering the shared pathogenetic mechanisms of obesity and CHIP, our objective in this review was to investigate both preclinical and clinical evidence regarding the correlation between obesity and CHIP and the resulting implications of this interaction on the pathophysiology of CVDs and malignancies. The pro-inflammatory condition induced by obesity and CHIP enhances the probability of developing both diseases and increases the likelihood of developing CVDs, T2DM and malignancies, suggesting that a dangerous vicious loop may exist. However, it is vital to conduct additional research that will suggest targeted treatment options for obese individuals with CHIP in order to reduce harmful effects connected to these conditions. Full article
(This article belongs to the Special Issue Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis)
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18 pages, 1452 KiB  
Review
Childhood Obesity: A Potential Key Factor in the Development of Glioblastoma Multiforme
by Punya Sachdeva, Shampa Ghosh, Soumya Ghosh, Sungsoo Han, Juni Banerjee, Rakesh Bhaskar and Jitendra Kumar Sinha
Life 2022, 12(10), 1673; https://doi.org/10.3390/life12101673 - 21 Oct 2022
Cited by 11 | Viewed by 4617
Abstract
Glioblastoma multiforme (GBM) is a malignant primary tumor type of the central nervous system (CNS). This type of brain tumor is rare and is responsible for 12–15% of all brain tumors. The typical survival rate of GBM is only 12 to 14 months. [...] Read more.
Glioblastoma multiforme (GBM) is a malignant primary tumor type of the central nervous system (CNS). This type of brain tumor is rare and is responsible for 12–15% of all brain tumors. The typical survival rate of GBM is only 12 to 14 months. GBM has a poor and unsatisfactory prognosis despite advances in research and therapeutic interventions via neurosurgery, radiation, and chemotherapy. The molecular heterogeneity, aggressive nature, and occurrence of drug-resistant cancer stem cells in GB restricts the therapeutic efficacy. Interestingly, the CNS tumors in children are the second most usual and persistent type of solid tumor. Since numerous research studies has shown the association between obesity and cancer, childhood obesity is one of the potential reasons behind the development of CNS tumors, including GBM. Obesity in children has almost reached epidemic rates in both developed and developing countries, harming children’s physical and mental health. Obese children are more likely to face obesity as adults and develop non-communicable diseases such as diabetes and cardiovascular disease as compared to adults with normal weight. However, the actual origin and cause of obesity are difficult to be pointed out, as it is assumed to be a disorder with numerous causes such as environmental factors, lifestyle, and cultural background. In this narrative review article, we discuss the various molecular and genetic drivers of obesity that can be targeted as potential contributing factors to fight the development of GBM in children. Full article
(This article belongs to the Special Issue Connections among Obesity, Diabetes, Steroidogenesis and Carcinogenesis)
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