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New Insights into Adipose Tissue Metabolic Function and Dysfunction 2.0

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Molecular Pathology, Diagnostics, and Therapeutics".

Deadline for manuscript submissions: 20 April 2024 | Viewed by 12305

Special Issue Editors


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Guest Editor
Department of Clinical and Experimental Medicine, University of Messina, Via C. Valeria, 98125 Messina, Italy
Interests: pharmacology; natural products; oxidative stress; inflammatory disease; atherosclerosis; metabolic disease; neurodegenerative diseases; autophagy; proliferation and differentiation process
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Special Issue Information

Dear Colleagues,

Adipose tissue is widely known as an endocrine organ able to modulate systemic metabolism thanks to its effects on energy storage, adipokine production, and adaptive thermogenesis. This endocrine function is carried out in various organs, such as liver, kidney, pancreas, and brain, and thus contributes to homeostatic regulation, energy balance, insulin sensitivity, and vascular–endothelial function.

The dysregulation of the differentiation, metabolism, and endocrine functions of adipocytes leads to adipose tissue dysfunction, which triggers the activation of molecular pathways involved in the physiopathology of overall metabolic diseases, such as obesity, inflammation, insulin resistance, and type 2 diabetes.

New therapeutic approaches targeting adipose tissue and its signaling molecules and heterogeneity could provide potential advances in understanding its pathophysiology and in treating several metabolic syndromes.

The purpose of this Special Issue of the International Journal of Molecular Sciences entitled “New Insights into Adipose Tissue Metabolic Function and Dysfunction” is to compile original research papers and/or relevant updates within the literature on new insights into the pathogenesis, molecular pathways, and beneficial effects of novel and safe treatments for metabolic diseases associated with adipose tissue disfunction.

Dr. Federica Mannino
Dr. Giovanni Pallio
Guest Editors

Manuscript Submission Information

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Keywords

  • inflammation
  • browning
  • thermogenesis
  • adipogenesis
  • diabetes
  • adipokines
  • energy storage
  • insulin resistance
  • obesity
  • lipolysis

Published Papers (8 papers)

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Research

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11 pages, 507 KiB  
Article
The Effect of Diesel Exhaust Particles on Adipose Tissue Mitochondrial Function and Inflammatory Status
by Cali E. Warren, Kennedy M. Campbell, Madison N. Kirkham, Erin R. Saito, Nicole P. Remund, Kevin B. Cayabyab, Iris J. Kim, Micah S. Heimuli, Paul R. Reynolds, Juan A. Arroyo and Benjamin T. Bikman
Int. J. Mol. Sci. 2024, 25(8), 4322; https://doi.org/10.3390/ijms25084322 (registering DOI) - 13 Apr 2024
Viewed by 112
Abstract
Air pollution poses a significant global health risk, with fine particulate matter (PM2.5) such as diesel exhaust particles (DEPs) being of particular concern due to their potential to drive systemic toxicities through bloodstream infiltration. The association between PM2.5 exposure and [...] Read more.
Air pollution poses a significant global health risk, with fine particulate matter (PM2.5) such as diesel exhaust particles (DEPs) being of particular concern due to their potential to drive systemic toxicities through bloodstream infiltration. The association between PM2.5 exposure and an increased prevalence of metabolic disorders, including obesity, metabolic syndrome, and type 2 diabetes mellitus (T2DM), is evident against a backdrop of rising global obesity and poor metabolic health. This paper examines the role of adipose tissue in mediating the effects of PM2.5 on metabolic health. Adipose tissue, beyond its energy storage function, is responsive to inhaled noxious stimuli, thus disrupting metabolic homeostasis and responding to particulate exposure with pro-inflammatory cytokine release, contributing to systemic inflammation. The purpose of this study was to characterize the metabolic response of adipose tissue in mice exposed to either DEPs or room air (RA), exploring both the adipokine profile and mitochondrial bioenergetics. In addition to a slight change in fat mass and a robust shift in adipocyte hypertrophy in the DEP-exposed animals, we found significant changes in adipose mitochondrial bioenergetics. Furthermore, the DEP-exposed animals had a significantly higher expression of adipose inflammatory markers compared with the adipose from RA-exposed mice. Despite the nearly exclusive focus on dietary factors in an effort to better understand metabolic health, these results highlight the novel role of environmental factors that may contribute to the growing global burden of poor metabolic health. Full article
18 pages, 4589 KiB  
Article
Consequences of COVID-19 on Adipose Tissue Signatures
by Sontje Krupka, Anne Hoffmann, Mariami Jasaszwili, Arne Dietrich, Esther Guiu-Jurado, Nora Klöting and Matthias Blüher
Int. J. Mol. Sci. 2024, 25(5), 2908; https://doi.org/10.3390/ijms25052908 - 02 Mar 2024
Viewed by 878
Abstract
Since the emergence of coronavirus disease-19 (COVID-19) in 2019, it has been crucial to investigate the causes of severe cases, particularly the higher rates of hospitalization and mortality in individuals with obesity. Previous findings suggest that adipocytes may play a role in adverse [...] Read more.
Since the emergence of coronavirus disease-19 (COVID-19) in 2019, it has been crucial to investigate the causes of severe cases, particularly the higher rates of hospitalization and mortality in individuals with obesity. Previous findings suggest that adipocytes may play a role in adverse COVID-19 outcomes in people with obesity. The impact of COVID-19 vaccination and infection on adipose tissue (AT) is currently unclear. We therefore analyzed 27 paired biopsies of visceral and subcutaneous AT from donors of the Leipzig Obesity BioBank that have been categorized into three groups (1: no infection/no vaccination; 2: no infection but vaccinated; 3: infected and vaccinated) based on COVID-19 antibodies to spike (indicating vaccination) and/or nucleocapsid proteins. We provide additional insights into the impact of COVID-19 on AT biology through a comprehensive histological transcriptome and serum proteome analysis. This study demonstrates that COVID-19 infection is associated with smaller average adipocyte size. The impact of infection on gene expression was significantly more pronounced in subcutaneous than in visceral AT and mainly due to immune system-related processes. Serum proteome analysis revealed the effects of the infection on circulating adiponectin, interleukin 6 (IL-6), and carbonic anhydrase 5A (CA5A), which are all related to obesity and blood glucose abnormalities. Full article
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14 pages, 3670 KiB  
Article
Bone Marrow Adipose Tissue Is Not Required for Reconstitution of the Immune System Following Irradiation in Male Mice
by Jessica A. Keune, Carmen P. Wong, Adam J. Branscum, Scott A. Menn, Urszula T. Iwaniec and Russell T. Turner
Int. J. Mol. Sci. 2024, 25(4), 1980; https://doi.org/10.3390/ijms25041980 - 06 Feb 2024
Viewed by 612
Abstract
Bone marrow adipose tissue (BMAT) is hypothesized to serve as an expandable/contractible fat depot which functions, in part, to minimize energy requirements for sustaining optimal hematopoiesis. We investigated whether BMAT is required for immune reconstitution following injury. Male wild type (WBB6F1, WT) and [...] Read more.
Bone marrow adipose tissue (BMAT) is hypothesized to serve as an expandable/contractible fat depot which functions, in part, to minimize energy requirements for sustaining optimal hematopoiesis. We investigated whether BMAT is required for immune reconstitution following injury. Male wild type (WBB6F1, WT) and BMAT-deficient WBB6F1/J-KitW/KitW-v/J (KitW/W-v) mice were lethally irradiated. Irradiation was followed by adoptive transfer of 1000 purified WT hematopoietic stem cells (HSCs). The extent of immune reconstitution in blood, bone marrow, and lymph nodes in the irradiated mice was determined using HSCs from green fluorescent protein (GFP)-expressing mice. We also evaluated skeletal response to treatment. Detection of GFP-positive B and T cells in peripheral blood at 4 and 9 weeks following adoptive transfer and in bone marrow and lymph nodes following necropsy revealed excellent immune reconstitution in both WT and BMAT-deficient mice. Adipocytes were numerous in the distal femur of WT mice but absent or rare in KitW/W-v mice. Bone parameters, including length, mass, density, bone volume, microarchitecture, and turnover balance, exhibited few differences between WT and BMAT-deficient mice. The minimal differences suggest that BMAT is not required for reconstitution of the immune system following lethal radiation and is not a major contributor to the skeletal phenotypes of kit signaling-deficient mice. Full article
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14 pages, 3864 KiB  
Article
Oral Intake of Inosine 5′-Monophosphate in Mice Promotes the Absorption of Exogenous Fatty Acids and Their Conversion into Triglycerides though Enhancing the Phosphorylation of Adenosine 5′-Monophosphate-Activated Protein Kinase in the Liver, Leading to Lipohyperplasia
by Bin Zhang, Yang Xu, Jinyan Liu, Chongming Wu, Xiaohong Zhao, Lidong Zhou and Yong Xie
Int. J. Mol. Sci. 2023, 24(19), 14588; https://doi.org/10.3390/ijms241914588 - 26 Sep 2023
Viewed by 757
Abstract
Inosine 5′-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-db/db (db/db) mice. Thus, IMP taken orally by healthy mice might also damage their health. To date, how IMP affects health after being [...] Read more.
Inosine 5′-monophoaphate (IMP) is a food additive that promotes serious lipohyperplasia in the liver of C57/KsJ-db/db (db/db) mice. Thus, IMP taken orally by healthy mice might also damage their health. To date, how IMP affects health after being taken by healthy animals is still unclear. Therefore, we investigated the health of C57BL/6J mice affected by IMP intake. Our data revealed that C57BL/6J mice administered 255 μM IMP daily via oral gavage for 4 months caused hyperlipidemia and an increase in body fat rate. The expressions of acetyl-CoA carboxylase 1 (ACC1) and phosphorylated acetyl-CoA carboxylase 2 (ACC2) in hepatocytes increased though the administration of IMP, promoting the phosphorylation of adenosine 5′-monophosphate-activated protein kinase (AMPK). The conversion of acetyl-CoA into triglycerides (TGs) was promoted by ACC1. These TGs were transported from the hepatocytes to avoid the development of non-alcoholic fatty liver disease (NAFLD), causing a deficiency of acetyl-CoA in the liver, and then, the increased phosphorylated ACC2 promoted the cytoplasm fatty acids entering the mitochondria and conversion into acetyl-CoA through the fatty acid β-oxidation pathway, causing a deficiency in fatty acids. Therefore, the liver showed enhanced absorption of exogenous fatty acids, which were converted into TGs, causing lipohyperplasia. In conclusion, an excessive IMP intake promotes metabolic dysfunction in adipose tissue. Full article
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24 pages, 6306 KiB  
Article
Efficacy of Carotenoid-Loaded Gelatin Nanoparticles in Reducing Plasma Cytokines and Adipocyte Hypertrophy in Wistar Rats
by Jaluza Luana C. de Queiroz, Isaiane Medeiros, Mayara S. R. Lima, Fabiana Maria C. de Carvalho, Christina S. Camillo, Pedro Paulo de A. Santos, Gerlane C. B. Guerra, Valéria C. da Silva, Helena T. Schroeder, Mauricio Krause, Ana Heloneida de A. Morais and Thaís S. Passos
Int. J. Mol. Sci. 2023, 24(13), 10657; https://doi.org/10.3390/ijms241310657 - 26 Jun 2023
Cited by 3 | Viewed by 1332
Abstract
The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized [...] Read more.
The present study investigated the effect of gelatin-based nanoparticles (EPG) loaded with a carotenoid-rich crude extract (CE) on systemic and adipose tissue inflammatory response in a model with inflammation induced by a high glycemic index and high glycemic load diet (HGLI). Nanoparticles synthesized were characterized by different physical and chemical methods. The in vivo investigation evaluated Wistar rats (n = 20, 11 days, adult male with 21 weeks) subdivided into untreated (HGLI diet), conventional treatment (nutritionally adequate diet), treatment 1 (HGLI + crude extract (12.5 mg/kg)), and treatment 2 (HGLI + EPG (50 mg/kg)) groups. Dietary intake, caloric intake and efficiency, weight, inflammatory cytokines tissue concentration, visceral adipose tissue (VAT) weight, histopathological analysis, and antioxidant activity in plasma and VAT were investigated. EPG showed the same physical and chemical characteristics as previous batches (95.2 nm, smooth surface, and chemical interactions between materials). The EPG-treated group was the only group promoting negative ∆dietary intake, ∆caloric efficiency, and ∆weight. In addition, it presented a significant reduction (p < 0.05) in IL-6 and leptin levels and a greater presence of multilocular adipocytes. The results suggest that EPG can act as a nutraceutical in adjuvant therapy for treating inflammatory diseases associated with adipose tissue accumulation. Full article
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Review

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15 pages, 290 KiB  
Review
The Effects of Intermittent Cold Exposure on Adipose Tissue
by Matthew C. Scott and Scott Fuller
Int. J. Mol. Sci. 2024, 25(1), 46; https://doi.org/10.3390/ijms25010046 - 19 Dec 2023
Viewed by 3467
Abstract
Intermittent cold exposure (ICE) has garnered increased attention in popular culture, largely for its proposed effects on mood and immune function, but there are also suggestions that the energy-wasting mechanisms associated with thermogenesis may decrease body weight and fat mass. Considering the continued [...] Read more.
Intermittent cold exposure (ICE) has garnered increased attention in popular culture, largely for its proposed effects on mood and immune function, but there are also suggestions that the energy-wasting mechanisms associated with thermogenesis may decrease body weight and fat mass. Considering the continued and worsening prevalence of obesity and type II diabetes, any protocol that can reduce body weight and/or improve metabolic health would be a substantial boon. Here, we present a narrative review exploring the research related to ICE and adipose tissue. Any publicly available original research examining the effects of repeated bouts of ICE on adipose-related outcomes was included. While ICE does not consistently lower body weight or fat mass, there does seem to be evidence for ICE as a positive modulator of the metabolic consequences of obesity, such as glucose tolerance and insulin signaling. Further, ICE consistently increases the activity of brown adipose tissue (BAT) and transitions white adipose tissue to a phenotype more in line with BAT. Lastly, the combined effects of ICE and exercise do not seem to provide any additional benefit, at least when exercising during ICE bouts. The majority of the current literature on ICE is based on rodent models where animals are housed in cold rooms, which does not reflect protocols likely to be implemented in humans such as cold water immersion. Future research could specifically characterize ICE via cold water immersion in combination with controlled calorie intake to clearly determine the effects of ICE as it would be implemented in humans looking to lower their body weight via reductions in fat mass. Full article
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23 pages, 4998 KiB  
Review
Physiological Approaches Targeting Cellular and Mitochondrial Pathways Underlying Adipose Organ Senescence
by Pieter de Lange, Assunta Lombardi, Elena Silvestri, Federica Cioffi, Antonia Giacco, Stefania Iervolino, Giuseppe Petito, Rosalba Senese, Antonia Lanni and Maria Moreno
Int. J. Mol. Sci. 2023, 24(14), 11676; https://doi.org/10.3390/ijms241411676 - 19 Jul 2023
Cited by 3 | Viewed by 1947
Abstract
The adipose organ is involved in many metabolic functions, ranging from the production of endocrine factors to the regulation of thermogenic processes. Aging is a natural process that affects the physiology of the adipose organ, leading to metabolic disorders, thus strongly impacting healthy [...] Read more.
The adipose organ is involved in many metabolic functions, ranging from the production of endocrine factors to the regulation of thermogenic processes. Aging is a natural process that affects the physiology of the adipose organ, leading to metabolic disorders, thus strongly impacting healthy aging. Cellular senescence modifies many functional aspects of adipose tissue, leading to metabolic alterations through defective adipogenesis, inflammation, and aberrant adipocytokine production, and in turn, it triggers systemic inflammation and senescence, as well as insulin resistance in metabolically active tissues, leading to premature declined physiological features. In the various aging fat depots, senescence involves a multiplicity of cell types, including mature adipocytes and immune, endothelial, and progenitor cells that are aging, highlighting their involvement in the loss of metabolic flexibility, one of the common features of aging-related metabolic disorders. Since mitochondrial stress represents a key trigger of cellular senescence, and senescence leads to the accumulation of abnormal mitochondria with impaired dynamics and hindered homeostasis, this review focuses on the beneficial potential of targeting mitochondria, so that strategies can be developed to manage adipose tissue senescence for the treatment of age-related metabolic disorders. Full article
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22 pages, 1090 KiB  
Review
Gene Therapy Based on Mesenchymal Stem Cells Derived from Adipose Tissue for the Treatment of Obesity and Its Metabolic Complications
by Marta Lopez-Yus, Maria Pilar García-Sobreviela, Raquel del Moral-Bergos and Jose M. Arbones-Mainar
Int. J. Mol. Sci. 2023, 24(8), 7468; https://doi.org/10.3390/ijms24087468 - 18 Apr 2023
Cited by 5 | Viewed by 2185
Abstract
Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, [...] Read more.
Obesity is a highly prevalent condition often associated with dysfunctional adipose tissue. Stem cell-based therapies have become a promising tool for therapeutic intervention in the context of regenerative medicine. Among all stem cells, adipose-derived mesenchymal stem cells (ADMSCs) are the most easily obtained, have immunomodulatory properties, show great ex vivo expansion capacity and differentiation to other cell types, and release a wide variety of angiogenic factors and bioactive molecules, such as growth factors and adipokines. However, despite the positive results obtained in some pre-clinical studies, the actual clinical efficacy of ADMSCs still remains controversial. Transplanted ADMSCs present a meager rate of survival and proliferation, possibly because of the damaged microenvironment of the affected tissues. Therefore, there is a need for novel approaches to generate more functional ADMSCs with enhanced therapeutic potential. In this context, genetic manipulation has emerged as a promising strategy. In the current review, we aim to summarize several adipose-focused treatments of obesity, including cell therapy and gene therapy. Particular emphasis will be given to the continuum from obesity to metabolic syndrome, diabetes, and underlying non-alcoholic fatty liver disease (NAFLD). Furthermore, we will provide insights into the potential shared adipocentric mechanisms involved in these pathophysiological processes and their remediation using ADMSCs. Full article
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