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Adipose Tissue as a Therapy and Therapeutic Target for Human...
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Adipose Tissue as a Therapy and Therapeutic Target for Human Diseases

A special issue of Pharmaceuticals (ISSN 1424-8247). This special issue belongs to the section "Pharmacology".

Deadline for manuscript submissions: closed (15 March 2024) | Viewed by 23199

Special Issue Editor

Dr. Ejaz Asim

E-Mail Website
Guest Editor
Department of Plastic Surgery, University of Pittsburgh, Pittsburgh, PA 15260, USA
Interests: adipose tissue aging; ASCs characterization; regenerative aging; wound healing

Special Issue Information

Dear Colleagues,

Adipose tissue is a dynamic organ that plays an important role in metabolic homeostasis via the storage of excess fat, maintaining nutrient balance, and immune modulation. Adipose tissue comprises a variety of cell types, mainly mature adipocytes, adipose-derived stem cells (ASCs), endothelial cells, and immune cells. ASCs play an important role in the regeneration of adipose tissue. Any defect or imbalance in adipose tissue maintenance and regeneration can result in metabolic disorders. Recently, adipose tissue has gained significant attention as a therapeutic target for treating metabolic disorders.

As adipose tissue is a readily available source of valuable cell types having regenerative and immunomodulation potential, adipose tissue and adipose-tissue-derived products can be harvested in large volumes and have been successfully used in clinics for tissue regeneration and reconstruction.

The unique character of adipose tissue as an organ responsible for energy storage, homeostasis, metabolic regulation, and as a source of regenerative components, has made it an ideal candidate as a regenerative therapy tool and as a therapeutic target to address metabolic disorders. This Special Issue aims to highlight the new therapeutic approaches and mechanistic studies targeted towards modulation of adipose tissue structure and function to treat metabolic disorders, as well as strategies employing adipose tissue as a therapeutic tool for tissue regeneration and reconstruction.

Dr. Ejaz Asim
Guest Editor

Manuscript Submission Information

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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 2900 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

  • adipose tissue
  • obesity
  • metabolic disorders
  • type 2 diabetes
  • insulin resistance
  • lipodystrophy
  • adipose-derived stem cells
  • inflammation
  • tissue regeneration
  • exosomes
  • wound healing

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Published Papers (5 papers)

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Research

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14 pages, 2256 KiB  
Article
Nicotinamide Riboside Improves Stemness of Human Adipose-Derived Stem Cells and Inhibits Terminal Adipocyte Differentiation
by Somaiah Chinnapaka, Hamid Malekzadeh, Zayaan Tirmizi, José A. Arellano and Asim Ejaz
Pharmaceuticals 2023, 16(8), 1134; https://doi.org/10.3390/ph16081134 - 10 Aug 2023
Cited by 1 | Viewed by 2217
Abstract
Adipose tissue plays a crucial role in maintaining metabolic homeostasis by serving as a storage site for excess fat and protecting other organs from the detrimental effects of lipotoxicity. However, the aging process is accompanied by a redistribution of fat, characterized by a [...] Read more.
Adipose tissue plays a crucial role in maintaining metabolic homeostasis by serving as a storage site for excess fat and protecting other organs from the detrimental effects of lipotoxicity. However, the aging process is accompanied by a redistribution of fat, characterized by a decrease in insulin-sensitive subcutaneous adipose depot and an increase in insulin-resistant visceral adipose depot. This age-related alteration in adipose tissue distribution has implications for metabolic health. Adipose-derived stem cells (ASCs) play a vital role in the regeneration of adipose tissue. However, aging negatively impacts the stemness and regenerative potential of ASCs. The accumulation of oxidative stress and mitochondrial dysfunction-associated cellular damage contributes to the decline in stemness observed in aged ASCs. Nicotinamide adenine dinucleotide (NAD+) is a crucial metabolite that is involved in maintaining cellular homeostasis and stemness. The dysregulation of NAD+ levels with age has been associated with metabolic disorders and the loss of stemness. In this study, we aimed to investigate the effects of nicotinamide riboside (NR), a precursor of NAD+, on the stemness of human ASCs in cell culture. Our findings reveal that adipogenesis is accompanied by an increase in mitochondrial activity and the production of reactive oxygen species (ROS). However, treatment with NR leads to a reduction in mitochondrial activity and ROS production in ASCs. Furthermore, NR administration improves the stemness-related genes expression in ASCs and mitigates their propensity for adipocyte differentiation. These results suggest that NR treatment holds promise as a potential strategy to rejuvenate the stemness of aged ASCs. Further investigations, including in vivo evaluations using animal models and human studies, will be necessary to validate these findings and establish the clinical potential of this well-established drug for enhancing the stemness of aged stem cells. Full article
(This article belongs to the Special Issue Adipose Tissue as a Therapy and Therapeutic Target for Human Diseases)
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12 pages, 5831 KiB  
Article
Repurposing Lenvatinib as A Potential Therapeutic Agent against Thyroid Eye Disease by Suppressing Adipogenesis in Orbital Adipose Tissues
by Lu Cheng, Jing Hu, Ling Zhang, Ning Shen, Hui Chen and Fang Zhang
Pharmaceuticals 2022, 15(11), 1305; https://doi.org/10.3390/ph15111305 - 22 Oct 2022
Cited by 2 | Viewed by 2089
Abstract
Thyroid eye disease (TED) is the most common orbital disease in adults. Targeting expanded orbital adipose tissue (OAT) removed by surgery has therapeutic potential. However, drugs targeting OAT are unavailable because of the lack of deciphering features of OAT. Here, we aimed to [...] Read more.
Thyroid eye disease (TED) is the most common orbital disease in adults. Targeting expanded orbital adipose tissue (OAT) removed by surgery has therapeutic potential. However, drugs targeting OAT are unavailable because of the lack of deciphering features of OAT. Here, we aimed to investigate the mechanism underlying OAT expansion and identify a drug targeting OAT in TED. We found an increasing number of adipocytes with smaller size in TED-derived OATs as compared with controls, indicating that hyperplasia rather than hypertrophy contributed to OAT enlargement in TED. Typically smaller-sized adipocytes in TED patient-derived OATs were noted to localize surrounding vessels. RNA sequencing revealed enriched vascular endothelial growth factor receptor (VEGFR) genes in adipocytes differentiated from preadipocytes of TED-derived stromal vascular fraction (SVF). Similarly, OATs in patients with TED also expressed a higher level of VEGFR-1 and -2. We induced adipogenesis in TED-derived SVF with or without Lenvatinib, an FDA-approved small-molecule VEGFR inhibitor. Lenvatinib significantly suppressed lipid accumulation in a dose-dependent manner. In conclusion, our study revealed the potential anti-adipogenic effect of Lenvatinib on the OAT of TED-affected patients. In addition to proposing a drug for TED treatment, this study shows the therapeutic potential of anti-adipogenesis drugs targeting the VEGF pathway. Full article
(This article belongs to the Special Issue Adipose Tissue as a Therapy and Therapeutic Target for Human Diseases)
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Review

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15 pages, 2448 KiB  
Review
Application of Adipose-Tissue Derived Products for Burn Wound Healing
by Hamid Malekzadeh, Zayaan Tirmizi, José A. Arellano, Francesco M. Egro and Asim Ejaz
Pharmaceuticals 2023, 16(9), 1302; https://doi.org/10.3390/ph16091302 - 14 Sep 2023
Cited by 7 | Viewed by 2421
Abstract
Burn injuries are a significant global health concern, leading to high morbidity and mortality. Deep burn injuries often result in delayed healing and scar formation, necessitating effective treatment options. Regenerative medicine, particularly cell therapy using adipose-derived stem cells (ASCs), has emerged as a [...] Read more.
Burn injuries are a significant global health concern, leading to high morbidity and mortality. Deep burn injuries often result in delayed healing and scar formation, necessitating effective treatment options. Regenerative medicine, particularly cell therapy using adipose-derived stem cells (ASCs), has emerged as a promising approach to improving burn wound healing and reducing scarring. Both in vitro and preclinical studies have demonstrated the efficacy of ASCs and the stromal vascular fraction (SVF) in addressing burn wounds. The application of ASCs for burn healing has been studied in various forms, including autologous or allogeneic cells delivered in suspension or within scaffolds in animal burn models. Additionally, ASC-derived non-cellular components, such as conditioned media or exosomes have shown promise. Injection of ASCs and SVF at burn sites have been demonstrated to enhance wound healing by reducing inflammation and promoting angiogenesis, epithelialization, and granulation tissue formation through their paracrine secretome. This review discusses the applications of adipose tissue derivatives in burn injury treatment, encompassing ASC transplantation, as well as the utilization of non-cellular components utilization for therapeutic benefits. The application of ASCs in burn healing in the future will require addressing donor variability, safety, and efficacy for successful clinical application. Full article
(This article belongs to the Special Issue Adipose Tissue as a Therapy and Therapeutic Target for Human Diseases)
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17 pages, 1321 KiB  
Review
Adipose Tissue Remodeling in Obesity: An Overview of the Actions of Thyroid Hormones and Their Derivatives
by Giuseppe Petito, Federica Cioffi, Nunzia Magnacca, Pieter de Lange, Rosalba Senese and Antonia Lanni
Pharmaceuticals 2023, 16(4), 572; https://doi.org/10.3390/ph16040572 - 10 Apr 2023
Cited by 14 | Viewed by 6146
Abstract
Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining [...] Read more.
Metabolic syndrome and obesity have become important health issues of epidemic proportions and are often the cause of related pathologies such as type 2 diabetes (T2DM), hypertension, and cardiovascular disease. Adipose tissues (ATs) are dynamic tissues that play crucial physiological roles in maintaining health and homeostasis. An ample body of evidence indicates that in some pathophysiological conditions, the aberrant remodeling of adipose tissue may provoke dysregulation in the production of various adipocytokines and metabolites, thus leading to disorders in metabolic organs. Thyroid hormones (THs) and some of their derivatives, such as 3,5-diiodo-l-thyronine (T2), exert numerous functions in a variety of tissues, including adipose tissues. It is known that they can improve serum lipid profiles and reduce fat accumulation. The thyroid hormone acts on the brown and/or white adipose tissues to induce uncoupled respiration through the induction of the uncoupling protein 1 (UCP1) to generate heat. Multitudinous investigations suggest that 3,3′,5-triiodothyronine (T3) induces the recruitment of brown adipocytes in white adipose depots, causing the activation of a process known as “browning”. Moreover, in vivo studies on adipose tissues show that T2, in addition to activating brown adipose tissue (BAT) thermogenesis, may further promote the browning of white adipose tissue (WAT), and affect adipocyte morphology, tissue vascularization, and the adipose inflammatory state in rats receiving a high-fat diet (HFD). In this review, we summarize the mechanism by which THs and thyroid hormone derivatives mediate adipose tissue activity and remodeling, thus providing noteworthy perspectives on their efficacy as therapeutic agents to counteract such morbidities as obesity, hypercholesterolemia, hypertriglyceridemia, and insulin resistance. Full article
(This article belongs to the Special Issue Adipose Tissue as a Therapy and Therapeutic Target for Human Diseases)
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17 pages, 2298 KiB  
Review
Capsaicin for Weight Control: “Exercise in a Pill” (or Just Another Fad)?
by Arpad Szallasi
Pharmaceuticals 2022, 15(7), 851; https://doi.org/10.3390/ph15070851 - 11 Jul 2022
Cited by 18 | Viewed by 9198
Abstract
Medical management of obesity represents a large unmet clinical need. Animal experiments suggest a therapeutic potential for dietary capsaicin, the pungent ingredient in hot chili peppers, to lose weight. This is an attractive theory since capsaicin has been a culinary staple for thousands [...] Read more.
Medical management of obesity represents a large unmet clinical need. Animal experiments suggest a therapeutic potential for dietary capsaicin, the pungent ingredient in hot chili peppers, to lose weight. This is an attractive theory since capsaicin has been a culinary staple for thousands of years and is generally deemed safe when consumed in hedonically acceptable, restaurant-like doses. This review critically evaluates the available experimental and clinical evidence for and against capsaicin as a weight control agent and comes to the conclusion that capsaicin is not a magic “exercise in a pill”, although there is emerging evidence that it may help restore a healthy gut microbiota. Full article
(This article belongs to the Special Issue Adipose Tissue as a Therapy and Therapeutic Target for Human Diseases)
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