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Adipose Tissue in Health and Diseases

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Cell Biology and Pathology".

Deadline for manuscript submissions: 31 May 2024 | Viewed by 17091

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Dr. Atefeh Rabiee

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Guest Editor

Department of Physiology & Pharmacology, Thomas J. Long School of Pharmacy, University of the Pacific, Stockton, CA 95211, USA
Interests: adipocyte biology; metabolism; physiology; obesity; type two diabetes; insulin signaling; omics

Dr. Ewa Bielczyk-Maczyńska

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Guest Editor

Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA
Interests: functional genomics; metabolism; cell biology; molecular biology

Special Issue Information

Dear Colleagues,

Adipose tissue (AT) is a highly complex metabolic organ that plays a role in regulating many aspects of whole-body physiology, including food intake, energy balance, insulin sensitivity, body temperature, and immune responses.

Beyond this, adipose tissue is highly heterogeneous. The health status and function of AT depends on the fat-storing adipocytes and the complex intercellular communication between the several cell types residing within the tissue. Heterogenous AT is not solely composed of mature adipocytes, but is additionally comprised of adipocyte precursors/stem cells, immune cells, blood cells, and lymphatic capillaries consisting of endothelial cells (ECs). Each anatomical fat depot differs in metabolic and hormonal profiles and has distinct physiological roles. The differential accumulation of specific depots therefore translates into different clinical outcomes.

A distinct feature of AT is its high degree of plasticity. Physiologic stimuli induce alterations in AT metabolism, structure, and phenotype to meet the needs of the organism. Limitations to this plasticity cause diminished or aberrant responses to physiologic cues and drive the progression of various diseases.

This Special Issue on "Adipose Tissue in Health and Disease" aims to provide up-to-date insight into the remarkable complexity of the adipose tissue heterogeneity and metabolism, while also casting a light on its dysregulation in the context of many different human diseases. These run the gamut from obesity and type two diabetes to the rare adipose tissue disorders, including multiple symmetric lipomatosis (MSL), lipedema and Dercum's disease (DD).

Dr. Atefeh Rabiee
Dr. Ewa Bielczyk-Maczyńska
Guest Editors

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Keywords

adipose tissue
heterogeneity
cell morphology
endocrine function
metabolism
fat disorder

Published Papers (12 papers)

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Research

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16 pages, 2029 KiB

Open AccessArticle

Thickness and Volume of Epicardial Adipose Tissue in Relation to Stiffness and Elasticity of Aorta Assessed by Computed Tomography Angiography

by Paweł Gać, Wojciech Hajdusianek, Aleksandra Żórawik, Piotr Macek, Małgorzata Poręba and Rafał Poręba

Biomedicines 2023, 11(6), 1617; https://doi.org/10.3390/biomedicines11061617 - 01 Jun 2023

Cited by 1 | Viewed by 1029

Abstract

Purpose. The aim of the study was to assess the importance of the measurements of thickness and volume of epicardial adipose tissue (EAT) in coronary computed tomography angiography (CCTA) as a predictive factor of increased stiffness and impaired elasticity of aorta. Methods and materials. The study involved a group of 97 patients (63.48 ± 8.50 years). In accordance with the medians of epicardial adipose tissue (EAT) parameters, aortic elasticity and stiffness parameters, patients were divided into subgroups: EAT thickness median 9.40 mm, EAT volume median 61.95 mL, EAT thickness index 5.08 mm/m² and EAT volume index 34.33 mL/m². Results. The mean coronary artery calcium score was 162.24 (±317.69). The mean aortic stiffness index was 4.18 (±0.81). The assessed mean aortic elasticity parameters were 3.29% (±2.37) and 0.12 cm²/dyn (±0.09) for strain and distensibility, respectively. A positive linear correlation was observed between EAT parameters and aortic stiffness (0.21), volume (0.51), thickness index (0.24), volume index (0.55) and, for aorta elasticity, a negative linear correlation between the following EAT parameters was observed: thickness (−0.32 and −0.30), volume (−0.49 and −0.48), thickness index (−0.34 and −0.31), volume index (−0.51 and −0.49) and aortic elasticity parameters (aorta strain and aorta distensibility, respectively). Conclusion. The study showed that CCTA illustrates a relationship between the parameters of EAT and an increased stiffness of the aorta, while the most predictive factor of stiffness was the volume index. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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14 pages, 3559 KiB

Open AccessArticle

The Transcriptomic Landscape of Age-Induced Changes in Human Visceral Fat and the Predicted Omentum-Liver Connectome in Males

by Diogo de Moraes, Felippe Mousovich-Neto, Sarah Santiloni Cury, Jakeline Oliveira, Jeferson dos Santos Souza, Paula Paccielli Freire, Maeli Dal-Pai-Silva, Marcelo Alves da Silva Mori, Geysson Javier Fernandez and Robson Francisco Carvalho

Biomedicines 2023, 11(5), 1446; https://doi.org/10.3390/biomedicines11051446 - 14 May 2023

Viewed by 1842

Abstract

Aging causes alterations in body composition. Specifically, visceral fat mass increases with age and is associated with age-related diseases. The pathogenic potential of visceral fat accumulation has been associated with its anatomical location and metabolic activity. Visceral fat may control systemic metabolism by secreting molecules that act in distal tissues, mainly the liver, through the portal vein. Currently, little is known about age-related changes in visceral fat in humans. Aiming to identify molecular and cellular changes occurring with aging in the visceral fat of humans, we analyzed publicly available transcriptomic data of 355 omentum samples from the Genotype-Tissue Expression portal (GTEx) of 20–79-year-old males and females. We identified the functional enrichment of genes associated with aging, inferred age-related changes in visceral fat cellularity by deconvolution analysis, profiled the senescence-associated secretory phenotype of visceral adipose tissue, and predicted the connectivity of the age-induced visceral fat secretome with the liver. We demonstrate that age induces alterations in visceral fat cellularity, synchronous to changes in metabolic pathways and a shift toward a pro-inflammatory secretory phenotype. Furthermore, our approach identified candidates such as ADIPOQ-ADIPOR1/ADIPOR2, FCN2-LPR1, and TF-TFR2 to mediate visceral fat-liver crosstalk in the context of aging. These findings cast light on how alterations in visceral fat with aging contribute to liver dysfunction and age-related disease etiology. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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Review

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14 pages, 1381 KiB

Open AccessReview

Impact of Obesity-Related Endoplasmic Reticulum Stress on Cancer and Associated Molecular Targets

by Joud AlBashtawi, Hend Al-Jaber, Sara Ahmed and Layla Al-Mansoori

Biomedicines 2024, 12(4), 793; https://doi.org/10.3390/biomedicines12040793 - 03 Apr 2024

Viewed by 509

Abstract

Obesity, characterized by excessive body fat, is closely linked to endoplasmic reticulum (ER) stress, leading to insulin resistance and type 2 diabetes. Inflammatory pathways like c-Jun N-terminal kinase (JNK) worsen insulin resistance, impacting insulin signaling. Moreover, ER stress plays a substantial role in cancer, influencing tumor cell survival and growth by releasing factors like vascular endothelial growth factor (VEGF). The unfolded protein response (UPR) is pivotal in this process, offering both pro-survival and apoptotic pathways. This review offers an extensive exploration of the sophisticated connection between ER stress provoked by obesity and its role in both the onset and advancement of cancer. It delves into the intricate interplay between oncogenic signaling and the pathways associated with ER stress in individuals who are obese. Furthermore, this review sheds light on potential therapeutic strategies aimed at managing ER stress induced by obesity, with a focus on addressing cancer initiation and progression. The potential to alleviate ER stress through therapeutic interventions, which may encompass the use of small molecules, FDA-approved medications, and gene therapy, holds great promise. A more in-depth examination of pathways such as UPR, ER-associated protein degradation (ERAD), autophagy, and epigenetic regulation has the potential to uncover innovative therapeutic approaches and the identification of predictive biomarkers. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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15 pages, 1003 KiB

Open AccessReview

Impact of Obesity and Lysosomal Dysfunction on Chemoresistance in Ovarian Cancer

by Boyun Kim and Jewon Jung

Biomedicines 2024, 12(3), 604; https://doi.org/10.3390/biomedicines12030604 - 07 Mar 2024

Viewed by 1112

Abstract

Obesity is recognized as a significant risk factor for ovarian cancer, with accumulating evidence highlighting its impact on disease progression and chemoresistance. This review synthesizes current research elucidating the link between obesity-induced lysosomal dysfunction and ovarian cancer chemoresistance. Epidemiological studies consistently demonstrate a positive correlation between body mass index (BMI) and ovarian cancer risk, attributed in part to the predilection of epithelial ovarian cancer cells for adipose tissue, particularly the omentum. Adipokines released from the omentum contribute to cancer-associated characteristics, including energy supply to cancer cells. Moreover, obesity-induced alterations in lysosomal function have been implicated in systemic inflammation and lipid metabolism dysregulation, further exacerbating cancer progression. Lysosomes play a crucial role in drug resistance, as evidenced by studies demonstrating their involvement in mediating resistance to chemotherapy in ovarian cancer cells. Recent findings suggest that pharmacological inhibition of lysosomal calcium channels sensitizes drug-resistant ovarian cancer cells to cisplatin treatment, highlighting the therapeutic potential of targeting lysosomal dysfunction in obesity-related chemoresistance. This review underscores the importance of understanding the multifaceted roles of lysosomes in obesity-related drug resistance and their implications for the development of targeted therapeutic interventions in ovarian cancer management. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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21 pages, 1155 KiB

Open AccessReview

The Therapeutic Potential of Pericytes in Bone Tissue Regeneration

by Assel Issabekova, Gulshakhar Kudaibergen, Aliya Sekenova, Aidar Dairov, Madina Sarsenova, Sholpan Mukhlis, Abay Temirzhan, Murat Baidarbekov, Saule Eskendirova and Vyacheslav Ogay

Biomedicines 2024, 12(1), 21; https://doi.org/10.3390/biomedicines12010021 - 20 Dec 2023

Viewed by 885

Abstract

Pericytes, as perivascular cells, are present in all vascularized organs and tissues, and they actively interact with endothelial cells in capillaries and microvessels. Their involvement includes functions like blood pressure regulation, tissue regeneration, and scarring. Studies have confirmed that pericytes play a crucial role in bone tissue regeneration through direct osteodifferentiation processes, paracrine actions, and vascularization. Recent preclinical and clinical experiments have shown that combining perivascular cells with osteogenic factors and tissue-engineered scaffolds can be therapeutically effective in restoring bone defects. This approach holds promise for addressing bone-related medical conditions. In this review, we have emphasized the characteristics of pericytes and their involvement in angiogenesis and osteogenesis. Furthermore, we have explored recent advancements in the use of pericytes in preclinical and clinical investigations, indicating their potential as a therapeutic resource in clinical applications. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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17 pages, 1187 KiB

Open AccessReview

The Impact of Maternal Obesity on Adipose Progenitor Cells

by Simon Lecoutre, Salwan Maqdasy, Mélanie Lambert and Christophe Breton

Biomedicines 2023, 11(12), 3252; https://doi.org/10.3390/biomedicines11123252 - 08 Dec 2023

Cited by 1 | Viewed by 1025

Abstract

The concept of Developmental Origin of Health and Disease (DOHaD) postulates that adult-onset metabolic disorders may originate from suboptimal conditions during critical embryonic and fetal programming windows. In particular, nutritional disturbance during key developmental stages may program the set point of adiposity and its associated metabolic diseases later in life. Numerous studies in mammals have reported that maternal obesity and the resulting accelerated growth in neonates may affect adipocyte development, resulting in persistent alterations in adipose tissue plasticity (i.e., adipocyte proliferation and storage) and adipocyte function (i.e., insulin resistance, impaired adipokine secretion, reduced thermogenesis, and higher inflammation) in a sex- and depot-specific manner. Over recent years, adipose progenitor cells (APCs) have been shown to play a crucial role in adipose tissue plasticity, essential for its development, maintenance, and expansion. In this review, we aim to provide insights into the developmental timeline of lineage commitment and differentiation of APCs and their role in predisposing individuals to obesity and metabolic diseases. We present data supporting the possible implication of dysregulated APCs and aberrant perinatal adipogenesis through epigenetic mechanisms as a primary mechanism responsible for long-lasting adipose tissue dysfunction in offspring born to obese mothers. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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11 pages, 553 KiB

Open AccessReview

MRI Methods to Visualize and Quantify Adipose Tissue in Health and Disease

by Katerina Nikiforaki and Kostas Marias

Biomedicines 2023, 11(12), 3179; https://doi.org/10.3390/biomedicines11123179 - 29 Nov 2023

Viewed by 798

Abstract

MRI is the modality of choice for a vast range of pathologies but also a sensitive probe into human physiology and tissue function. For this reason, several methodologies have been developed and continuously evolve in order to non-invasively monitor underlying phenomena in human adipose tissue that were difficult to assess in the past through visual inspection of standard imaging modalities. To this end, this work describes the imaging methodologies used in medical practice and lists the most important quantitative markers related to adipose tissue physiology and pathology that are currently supporting diagnosis, longitudinal evaluation and patient management decisions. The underlying physical principles and the resulting markers are presented and associated with frequently encountered pathologies in radiology in order to set the frame of the ability of MRI to reveal the complex role of adipose tissue, not as an inert tissue but as an active endocrine organ. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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15 pages, 2128 KiB

Open AccessReview

The Role of NAD⁺ in Metabolic Regulation of Adipose Tissue: Implications for Obesity-Induced Insulin Resistance

by Tatjana Ruskovska and David A. Bernlohr

Biomedicines 2023, 11(9), 2560; https://doi.org/10.3390/biomedicines11092560 - 18 Sep 2023

Viewed by 1781

Abstract

Obesity-induced insulin resistance is among the key factors in the development of type 2 diabetes, atherogenic dyslipidemia and cardiovascular disease. Adipose tissue plays a key role in the regulation of whole-body metabolism and insulin sensitivity. In obesity, adipose tissue becomes inflamed and dysfunctional, exhibiting a modified biochemical signature and adipokine secretion pattern that promotes insulin resistance in peripheral tissues. An important hallmark of dysfunctional obese adipose tissue is impaired NAD⁺/sirtuin signaling. In this chapter, we summarize the evidence for impairment of the NAD⁺/sirtuin pathway in obesity, not only in white adipose tissue but also in brown adipose tissue and during the process of beiging, together with correlative evidence from human studies. We also describe the role of PARPs and CD38 as important NAD⁺ consumers and discuss findings from experimental studies that investigated potential NAD⁺ boosting strategies and their efficacy in restoring impaired NAD⁺ metabolism in dysfunctional obese adipose tissue. In sum, these studies suggest a critical role of NAD⁺ metabolism in adipose biology and provide a basis for the potential development of strategies to restore metabolic health in obesity. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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22 pages, 3757 KiB

Open AccessReview

Insulin Resistance and Hypertension: Mechanisms Involved and Modifying Factors for Effective Glucose Control

by Hussein F. Sakr, Srinivasa Rao Sirasanagandla, Srijit Das, Abdulhadi I. Bima and Ayman Z. Elsamanoudy

Biomedicines 2023, 11(8), 2271; https://doi.org/10.3390/biomedicines11082271 - 15 Aug 2023

Cited by 3 | Viewed by 2091

Abstract

Factors such as aging, an unhealthy lifestyle with decreased physical activity, snacking, a standard Western diet, and smoking contribute to raising blood pressure to a dangerous level, increasing the risk of coronary artery disease and heart failure. Atherosclerosis, or aging of the blood vessels, is a physiological process that has accelerated in the last decades by the overconsumption of carbohydrates as the primary sources of caloric intake, resulting in increased triglycerides and VLDL-cholesterol and insulin spikes. Classically, medications ranging from beta blockers to angiotensin II blockers and even calcium channel blockers were used alone or in combination with lifestyle modifications as management tools in modern medicine to control arterial blood pressure. However, it is not easy to control blood pressure or the associated complications. A low-carbohydrate, high-fat (LCHF) diet can reduce glucose and insulin spikes, improve insulin sensitivity, and lessen atherosclerosis risk factors. We reviewed articles describing the etiology of insulin resistance (IR) and its impact on arterial blood pressure from databases including PubMed, PubMed Central, and Google Scholar. We discuss how the LCHF diet is beneficial to maintaining arterial blood pressure at normal levels, slowing down the progression of atherosclerosis, and reducing the use of antihypertensive medications. The mechanisms involved in IR associated with hypertension are also highlighted. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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12 pages, 311 KiB

Open AccessReview

Allergic Diseases and Childhood Obesity: A Detrimental Link?

by Camilla Stefani, Luca Pecoraro, Carl-Erik Flodmark, Marco Zaffanello, Giorgio Piacentini and Angelo Pietrobelli

Biomedicines 2023, 11(7), 2061; https://doi.org/10.3390/biomedicines11072061 - 22 Jul 2023

Cited by 2 | Viewed by 1872

Abstract

Several epidemiological studies have described childhood obesity as a risk factor for atopic disease, particularly asthma. At the same time, this association seems to be more conflicting for allergic rhinitis, atopic dermatitis, and chronic urticaria. This article aims to deepen the possibility of a relationship between childhood obesity and allergic diseases. As regards asthma, the mechanical and inflammatory effects of obesity can lead to its development. In addition, excess adiposity is associated with increased production of inflammatory cytokines and adipokines, leading to low-grade systemic inflammation and an increased risk of asthma exacerbations. Allergic rhinitis, atopic dermatitis, food allergies, and chronic urticaria also seem to be related to this state of chronic low-grade systemic inflammation typical of obese children. Vitamin D deficiency appears to play a role in allergic rhinitis, while dyslipidemia and skin barrier defects could explain the link between obesity and atopic dermatitis. Starting from this evidence, it becomes of fundamental importance to act on body weight control to achieve general and allergic health, disentangling the detrimental link between obesity allergic diseases and childhood obesity. Further studies on the association between adiposity and atopy are needed, confirming the biologically active role of fat tissue in the development of allergic diseases and exploring the possibility of new therapeutic strategies. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

18 pages, 1010 KiB

Open AccessReview

Type II Transmembrane Serine Proteases as Modulators in Adipose Tissue Phenotype and Function

by Qingyu Wu, Shuo Li, Xianrui Zhang and Ningzheng Dong

Biomedicines 2023, 11(7), 1794; https://doi.org/10.3390/biomedicines11071794 - 23 Jun 2023

Cited by 3 | Viewed by 2063

Abstract

Adipose tissue is a crucial organ in energy metabolism and thermoregulation. Adipose tissue phenotype is controlled by various signaling mechanisms under pathophysiological conditions. Type II transmembrane serine proteases (TTSPs) are a group of trypsin-like enzymes anchoring on the cell surface. These proteases act in diverse tissues to regulate physiological processes, such as food digestion, salt-water balance, iron metabolism, epithelial integrity, and auditory nerve development. More recently, several members of the TTSP family, namely, hepsin, matriptase-2, and corin, have been shown to play a role in regulating lipid metabolism, adipose tissue phenotype, and thermogenesis, via direct growth factor activation or indirect hormonal mechanisms. In mice, hepsin deficiency increases adipose browning and protects from high-fat diet-induced hyperglycemia, hyperlipidemia, and obesity. Similarly, matriptase-2 deficiency increases fat lipolysis and reduces obesity and hepatic steatosis in high-fat diet-fed mice. In contrast, corin deficiency increases white adipose weights and cell sizes, suppresses adipocyte browning and thermogenic responses, and causes cold intolerance in mice. These findings highlight an important role of TTSPs in modifying cellular phenotype and function in adipose tissue. In this review, we provide a brief description about TTSPs and discuss recent findings regarding the role of hepsin, matriptase-2, and corin in regulating adipose tissue phenotype, energy metabolism, and thermogenic responses. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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11 pages, 1383 KiB

Open AccessBrief Report

Laminin α4 Expression in Human Adipose Tissue Depots and Its Association with Obesity and Obesity Related Traits

by Tobias Hagemann, Paul Czechowski, Adhideb Ghosh, Wenfei Sun, Hua Dong, Falko Noé, Christian Wolfrum, Matthias Blüher and Anne Hoffmann

Biomedicines 2023, 11(10), 2806; https://doi.org/10.3390/biomedicines11102806 - 17 Oct 2023

Viewed by 920

Abstract

Laminin α4 (LAMA4) is one of the main structural adipocyte basement membrane (BM) components that is upregulated during adipogenesis and related to obesity in mice and humans. We conducted RNA-seq-based gene expression analysis of LAMA4 in abdominal subcutaneous (SC) and visceral (VIS) adipose tissue (AT) depots across three human sub-cohorts of the Leipzig Obesity BioBank (LOBB) to explore the relationship between LAMA4 expression and obesity (N = 1479) in the context of weight loss (N = 65) and metabolic health (N = 42). We found significant associations of LAMA4 with body fat mass (p < 0.001) in VIS AT; higher expression in VIS AT compared to SC AT; and significant relation to metabolic health parameters e.g., body fat in VIS AT, waist (p = 0.009) and interleukin 6 (p = 0.002) in male VIS AT, and hemoglobin A1c (p = 0.008) in male SC AT. AT LAMA4 expression was not significantly different between subjects with or without obesity, metabolically healthy versus unhealthy, and obesity before versus after short-term weight loss. Our results support significant associations between obesity related clinical parameters and elevated LAMA4 expression in humans. Our work offers one of the first references for understanding the meaning of LAMA4 expression specifically in relation to obesity based on large-scale RNA-seq data. Full article

(This article belongs to the Special Issue Adipose Tissue in Health and Diseases)

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