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Role of Fatty Acid-Induced Multi-Organ Damage on Diabetes Onset and...
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Role of Fatty Acid-Induced Multi-Organ Damage on Diabetes Onset and Progression: Implications for Therapeutic Strategies

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Lipids".

Deadline for manuscript submissions: closed (15 February 2023) | Viewed by 11196

Special Issue Editors

Dr. Annalisa Natalicchio

E-Mail Website
Guest Editor
Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari, 70124 Bari, Italy
Interests: type 2 diabetes; islets of Langerhans; pancreatic beta-cell; insulin secretion; incretin hormones; irisin
Dr. Nicola Marrano

E-Mail Website
Guest Editor
Department of Emergency and Organ Transplantation, Section of Internal Medicine, Endocrinology, Andrology and Metabolic Diseases, University of Bari, 70124 Bari, Italy
Interests: islets of Langerhans; pancreatic beta-cell; insulin secretion; apoptosis; incretin hormones; irisin

Special Issue Information

Dear Colleagues,

It is well known that an excessive fat accumulation presents a risk to health. When the dietary fat surfeit exceeds the normal capacity of adipose tissue to store excessive diet-derived triglycerides (TG), cholesterol and free fatty acids (FFAs), the levels of plasma lipids increase and they accumulate in ectopic sites (i.e., heart, endothelium, liver, skeletal muscle, pancreas, kidney, etc.). The chronic excess of ectopic FFAs leads to the accrual of toxic metabolic derivatives which are detrimental for the cells and results in organs damage, a condition defined lipotoxicity. Lipotoxicity plays a key role in the onset/progression of diabetes, particularly type 2, and its complications, therefore, to know the mechanisms underlying the lipotoxic damage and to identify strategies to prevent or correct it would represent a valid approach to counteract diabetes development and progression.

This Special Issue will focus on the role of fatty acids-induced multi-organ damage on diabetes onset and progression, and its implication for new therapeutic strategies. Original manuscripts and reviews dealing with any aspect of molecular mechanisms and clinical outcomes of lipotoxicity in diabetes are very welcome.

Dr. Annalisa Natalicchio
Dr. Nicola Marrano
Guest Editors

Manuscript Submission Information

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

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Please visit the Instructions for Authors page before submitting a manuscript. The Article Processing Charge (APC) for publication in this open access journal is 2700 CHF (Swiss Francs). Submitted papers should be well formatted and use good English. Authors may use MDPI's English editing service prior to publication or during author revisions.

Keywords

  • diabetes
  • lipotoxicity
  • fatty acids
  • organ damage
  • new therapeutic strategies  

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Published Papers (3 papers)

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Research

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13 pages, 356 KiB  
Article
Association between Higher Circulating Leucine-Rich α-2 Glycoprotein 1 Concentrations and Specific Plasma Ceramides in Postmenopausal Women with Type 2 Diabetes
by Alessandro Mantovani, Alessandro Csermely, Elena Sani, Giorgia Beatrice, Graziana Petracca, Gianluigi Lunardi, Stefano Bonapace, Giuseppe Lippi and Giovanni Targher
Biomolecules 2022, 12(7), 943; https://doi.org/10.3390/biom12070943 - 5 Jul 2022
Cited by 1 | Viewed by 2136
Abstract
Background: Although ceramides are involved in the pathophysiology of cardiovascular disease and other inflammation-associated disorders, there is a paucity of data on the association between plasma ceramides and inflammatory biomarkers in type 2 diabetes mellitus (T2DM). Therefore, we explored whether there was an [...] Read more.
Background: Although ceramides are involved in the pathophysiology of cardiovascular disease and other inflammation-associated disorders, there is a paucity of data on the association between plasma ceramides and inflammatory biomarkers in type 2 diabetes mellitus (T2DM). Therefore, we explored whether there was an association between plasma leucine-rich α-2 glycoprotein 1 (LRG1) concentrations (i.e., a novel proinflammatory signaling molecule) and specific plasma ceramides in postmenopausal women with T2DM. Methods: We measured six previously identified plasma ceramides, which have been associated with increased cardiovascular risk [plasma Cer(d18:1/16:0), Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d18:1/22:0), Cer(d18:1/24:0) and Cer(d18:1/24:1)], amongst 99 Caucasian postmenopausal women with non-insulin-treated T2DM (mean age 72 ± 8 years, mean hemoglobin A1c 6.9 ± 0.7%), who consecutively attended our diabetes outpatient service during a 3-month period. Plasma ceramide and LRG1 concentrations were measured with a targeted liquid chromatography-tandem mass spectrometry assay and a Milliplex® MAP human cardiovascular disease magnetic bead kit, respectively. Results: In linear regression analyses, higher plasma LRG1 levels (1st tertile vs. 2nd and 3rd tertiles combined) were associated with higher levels of plasma Cer(d18:1/16:0) (standardized β coefficient: 0.289, p = 0.004), Cer(d18:1/18:0) (standardized β coefficient: 0.307, p = 0.002), Cer(d18:1/20:0) (standardized β coefficient: 0.261, p = 0.009) or Cer(d18:1/24:1) (standardized β coefficient: 0.343, p < 0.001). These associations remained significant even after adjusting for age, body mass index, systolic blood pressure, total cholesterol level, hemoglobin A1c, insulin resistance and statin use. Conclusions: The results of our pilot exploratory study suggest that higher plasma LRG1 concentration was associated with higher levels of specific high-risk plasma ceramide molecules in elderly postmenopausal women with metabolically well-controlled T2DM, even after adjusting for known cardiovascular risk factors and other potential confounding variables. Full article
(This article belongs to the Special Issue Role of Fatty Acid-Induced Multi-Organ Damage on Diabetes Onset and Progression: Implications for Therapeutic Strategies)
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Review

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22 pages, 958 KiB  
Review
Type 2 Diabetes and Alzheimer’s Disease: The Emerging Role of Cellular Lipotoxicity
by Nicola Marrano, Giuseppina Biondi, Anna Borrelli, Martina Rella, Tommaso Zambetta, Ludovico Di Gioia, Mariangela Caporusso, Giancarlo Logroscino, Sebastio Perrini, Francesco Giorgino and Annalisa Natalicchio
Biomolecules 2023, 13(1), 183; https://doi.org/10.3390/biom13010183 - 16 Jan 2023
Cited by 15 | Viewed by 4896
Abstract
Type 2 diabetes (T2D) and Alzheimer’s diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates that AD is a significant comorbidity of T2D, and there is a ~1.4–2-fold increase in the risk of [...] Read more.
Type 2 diabetes (T2D) and Alzheimer’s diseases (AD) represent major health issues that have reached alarming levels in the last decades. Although growing evidence demonstrates that AD is a significant comorbidity of T2D, and there is a ~1.4–2-fold increase in the risk of developing AD among T2D patients, the involvement of possible common triggers in the pathogenesis of these two diseases remains largely unknown. Of note, recent mechanistic insights suggest that lipotoxicity could represent the missing ring in the pathogenetic mechanisms linking T2D to AD. Indeed, obesity, which represents the main cause of lipotoxicity, has been recognized as a major risk factor for both pathological conditions. Lipotoxicity can lead to inflammation, insulin resistance, oxidative stress, ceramide and amyloid accumulation, endoplasmic reticulum stress, ferroptosis, and autophagy, which are shared biological events in the pathogenesis of T2D and AD. In the current review, we try to provide a critical and comprehensive view of the common molecular pathways activated by lipotoxicity in T2D and AD, attempting to summarize how these mechanisms can drive future research and open the way to new therapeutic perspectives. Full article
(This article belongs to the Special Issue Role of Fatty Acid-Induced Multi-Organ Damage on Diabetes Onset and Progression: Implications for Therapeutic Strategies)
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Other

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10 pages, 1549 KiB  
Systematic Review
Liver Stiffness, Albuminuria and Chronic Kidney Disease in Patients with NAFLD: A Systematic Review and Meta-Analysis
by Stefano Ciardullo, Cinzia Ballabeni, Roberto Trevisan and Gianluca Perseghin
Biomolecules 2022, 12(1), 105; https://doi.org/10.3390/biom12010105 - 8 Jan 2022
Cited by 25 | Viewed by 3543
Abstract
An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus [...] Read more.
An association between liver stiffness, a surrogate measure of liver fibrosis, and chronic kidney disease (CKD) in patients with nonalcoholic fatty liver disease (NAFLD) has been proposed. However, most studies were small and had low statistical power. We systematically searched PubMed-MEDLINE and Scopus from inception to August 2021 for cross-sectional or cohort studies reporting the association between liver stiffness diagnosed by vibration controlled transient elastography (VCTE) and renal dysfunction. The primary outcome was CKD, defined as a composite of urinary albumin to creatinine ratio (UACR) ≥ 30 mg/g and estimated glomerular filtration rate (eGFR) < 60 mL/min/1.73 m2. Measures of association from individual studies were meta-analyzed using random effects models. Of the 526 titles initially scrutinized, 7 cross-sectional studies fulfilled the criteria and were included. For CKD, risk was higher in patients with liver fibrosis assessed by VCTE, compared with patients without (n = 5 studies: OR 2.49, 95% CI 1.89–3.29; test for overall effect z = 6.475, p < 0.001). When increased UACR was considered as an outcome, elevated liver stiffness was associated with a significantly increased risk as well (n = 3 studies: OR 1. 98 95% CI 1.29–3.05; test for overall effect z = 3.113, p = 0.002). Neither analysis showed significant heterogeneity (I2 = 0% and I2 = 46.5%, respectively for the two outcomes). This meta-analysis indicates that elevated liver stiffness is associated with increased odds of kidney outcomes among patients with NAFLD. Wider use of VCTE to screen for advanced fibrosis might help identify patients at risk of end-stage renal disease. Full article
(This article belongs to the Special Issue Role of Fatty Acid-Induced Multi-Organ Damage on Diabetes Onset and Progression: Implications for Therapeutic Strategies)
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