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Special Issue "Adipogenesis and Adipose Tissue Metabolism 2.0"

A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 September 2020).

Special Issue Editors

Prof. Dr. Encarnación Capilla
Website
Guest Editor
Universitat de Barcelona, Facultat de Biologia, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Barcelona, Spain
Interests: adipogenesis; adipocytes; white adipose tissue; adipokines; lipid metabolism; oxidative stress; obesity; lipodistrophy; metabolic syndrome; comparative endocrinology
Special Issues and Collections in MDPI journals
Prof. Dr. Isabel Navarro
Website
Guest Editor
Universitat de Barcelona, Facultat de Biologia, Departament de Biologia Cel·lular, Fisiologia i Immunologia, Barcelona, Spain
Special Issues and Collections in MDPI journals

Special Issue Information

Dear Colleagues,

Adipocytes are the major cellular constituent of adipose tissue, which exhibits different morphology and functions depending on the main types of adipocytes that compose it (white, brown, and beige). Two possible growth mechanisms of adipose tissue include hypertrophy (lipid accumulation within existing adipocytes) and hyperplasia (increase in cell number) through the process of adipogenesis. As a major source of energy storage, white adipose tissue has been largely considered to be a key metabolic organ. Nonetheless, despite the traditional view as a rather passive storage organ, adipose tissue has been later recognized as a multi-functional endocrine organ that plays a critical role in modulating not only whole-body energy metabolism and homeostasis, but also several other physiological processes, such as appetite and tissue inflammation responses. Henceforth, studies on the functional, developmental, and pathophysiological aspects of adipose tissue are of utmost importance. Thus, the aim of this Special Issue is to gather both reviews and research articles unraveling the mechanisms that underlie adipocyte differentiation as well as adipokines production and function to identify the major contributor(s) of obesity and lipid metabolism-related diseases, while works covering new insights into fundamental aspects of hormonal control of adipose tissue metabolism are also desirable.

Prof. Dr. Encarnación Capilla
Prof. Dr. Isabel Navarro
Guest Editors

Manuscript Submission Information

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Keywords

  • adipogenesis
  • adipocytes
  • white adipose tissue
  • adipokines
  • lipid metabolism
  • oxidative stress
  • obesity
  • lipodistrophy
  • metabolic syndrome
  • comparative endocrinology

Related Special Issue

Published Papers (9 papers)

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Research

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Open AccessArticle
A Novel Role for the DNA Repair Enzyme 8-Oxoguanine DNA Glycosylase in Adipogenesis
Int. J. Mol. Sci. 2021, 22(3), 1152; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms22031152 - 25 Jan 2021
Viewed by 474
Abstract
Cells sustain constant oxidative stress from both exogenous and endogenous sources. When unmitigated by antioxidant defenses, reactive oxygen species damage cellular macromolecules, including DNA. Oxidative lesions in both nuclear and mitochondrial DNA are repaired via the base excision repair (BER) pathway, initiated by [...] Read more.
Cells sustain constant oxidative stress from both exogenous and endogenous sources. When unmitigated by antioxidant defenses, reactive oxygen species damage cellular macromolecules, including DNA. Oxidative lesions in both nuclear and mitochondrial DNA are repaired via the base excision repair (BER) pathway, initiated by DNA glycosylases. We have previously demonstrated that the BER glycosylase 8-oxoguanine DNA glycosylase (OGG1) plays a novel role in body weight maintenance and regulation of adiposity. Specifically, mice lacking OGG1 (Ogg1−/−) are prone to increased fat accumulation with age and consumption of hypercaloric diets. Conversely, transgenic animals with mitochondrially-targeted overexpression of OGG1 (Ogg1Tg) are resistant to age- and diet-induced obesity. Given these phenotypes of altered adiposity in the context of OGG1 genotype, we sought to determine if OGG1 plays a cell-intrinsic role in adipocyte maturation and lipid accumulation. Here, we report that preadipocytes from Ogg1−/− mice differentiate more efficiently and accumulate more lipids than those from wild-type animals. Conversely, OGG1 overexpression significantly blunts adipogenic differentiation and lipid accretion in both pre-adipocytes from Ogg1Tg mice, as well as in 3T3-L1 cells with adenovirus-mediated OGG1 overexpression. Mechanistically, changes in adipogenesis are accompanied by significant alterations in cellular PARylation, corresponding with OGG1 genotype. Specifically, deletion of OGG1 reduces protein PARylation, concomitant with increased adipogenic differentiation, while OGG1 overexpression significantly increases PARylation and blunts adipogenesis. Collectively, these data indicate a novel role for OGG1 in modulating adipocyte differentiation and lipid accretion. These findings have important implications to our knowledge of the fundamental process of adipocyte differentiation, as well as to our understanding of lipid-related diseases such as obesity. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Open AccessArticle
Altered Regulation of adipomiR Editing with Aging
Int. J. Mol. Sci. 2020, 21(18), 6899; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21186899 - 20 Sep 2020
Viewed by 579
Abstract
Adipose dysfunction with aging increases risk to insulin resistance and other chronic metabolic diseases. We previously showed functional changes in microRNAs involved in pre-adipocyte differentiation with aging resulting in adipose dysfunction. However, the mechanisms leading to this dysfunction in microRNAs in adipose tissue [...] Read more.
Adipose dysfunction with aging increases risk to insulin resistance and other chronic metabolic diseases. We previously showed functional changes in microRNAs involved in pre-adipocyte differentiation with aging resulting in adipose dysfunction. However, the mechanisms leading to this dysfunction in microRNAs in adipose tissue (adipomiRs) during aging are not well understood. We determined the longitudinal changes in expression of adipomiRs and studied their regulatory mechanisms, such as miRNA biogenesis and editing, in an aging rodent model, with Fischer344 × Brown-Norway hybrid rats at ages ranging from 3 to 30 months (male/females, n > 8). Expression of adipomiRs and their edited forms were determined by small-RNA sequencing. RT-qPCR was used to measure the mRNA expression of biogenesis and editing enzymes. Sanger sequencing was used to validate editing with aging. Differential expression of adipomiRs involved in adipocyte differentiation and insulin signaling was altered with aging. Sex- and age-specific changes in edited adipomiRs were observed. An increase in miRNA biogenesis and editing enzymes (ADARs and their splice variants) were observed with increasing age, more so in female than male rats. The adipose dysfunction observed with age is attributed to differences in editing of adipomiRs, suggesting a novel regulatory pathway in aging. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Open AccessArticle
Genistein Induces Adipogenic and Autophagic Effects in Rainbow Trout (Oncorhynchus mykiss) Adipose Tissue: In Vitro and In Vivo Models
Int. J. Mol. Sci. 2020, 21(16), 5884; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21165884 - 16 Aug 2020
Viewed by 480
Abstract
Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE [...] Read more.
Soybeans are one of the most used alternative dietary ingredients in aquafeeds. However, they contain phytoestrogens like genistein (GE), which can have an impact on fish metabolism and health. This study aimed to investigate the in vitro and in vivo effects of GE on lipid metabolism, apoptosis, and autophagy in rainbow trout (Oncorhynchus mykiss). Primary cultured preadipocytes were incubated with GE at different concentrations, 10 or 100 μM, and 1 μM 17β-estradiol (E2). Furthermore, juveniles received an intraperitoneal injection of GE at 5 or 50 µg/g body weight, or E2 at 5 µg/g. In vitro, GE 100 μM increased lipid accumulation and reduced cell viability, apparently involving an autophagic process, indicated by the higher LC3-II protein levels, and higher lc3b and cathepsin d transcript levels achieved after GE 10 μM. In vivo, GE 50 µg/g upregulated the gene expression of fatty acid synthase (fas) and glyceraldehyde-3-phosphate dehydrogenase in adipose tissue, suggesting enhanced lipogenesis, whereas it increased hormone-sensitive lipase in liver, indicating a lipolytic response. Besides, autophagy-related genes increased in the tissues analyzed mainly after GE 50 µg/g treatment. Overall, these findings suggest that an elevated GE administration could lead to impaired adipocyte viability and lipid metabolism dysregulation in rainbow trout. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Open AccessArticle
Caveolae-Associated Protein 3 (Cavin-3) Influences Adipogenesis via TACE-Mediated Pref-1 Shedding
Int. J. Mol. Sci. 2020, 21(14), 5000; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21145000 - 15 Jul 2020
Viewed by 539
Abstract
Abnormal adipogenesis regulation is accompanied by a variety of metabolic dysfunctions and disorders. Caveolae play an important role in the regulation of fat production, modulated by caveolae-associated proteins (Cavin-1 to 4). Here, we investigated the role of Cavin-3 in lipogenesis and adipocyte differentiation, [...] Read more.
Abnormal adipogenesis regulation is accompanied by a variety of metabolic dysfunctions and disorders. Caveolae play an important role in the regulation of fat production, modulated by caveolae-associated proteins (Cavin-1 to 4). Here, we investigated the role of Cavin-3 in lipogenesis and adipocyte differentiation, as the regulatory functions and roles of Cavin-3 in adipocytes are unknown. A Cavin-3 knockdown/overexpression stable cell line was established, and adipogenesis-related gene and protein expression changes were investigated by real-time quantitative PCR and Western blot analysis, respectively. Additionally, confocal immune-fluorescence microscopy was used to verify the intracellular position of the relevant factors. The results showed that Cavin-3 mRNA and protein expression were elevated, along with physiological factors such as lipid droplet formation, during adipogenesis. Cavin-3 silencing resulted in retarded adipocyte differentiation, and its overexpression accelerated this process. Furthermore, Cavin-3 knockdown resulted in decreased expression of adipogenesis-related genes, such as PPAR-γ, FAS, aP2, and Adipoq, whereas preadipocyte factor-1 (Pref-1) was markedly increased during adipocyte maturation. Overall, Cavin-3 influences caveolar stability and modulates the tumor necrosis factor-alpha-converting enzyme (TACE)-mediated Pref-1 shedding process in both mouse and human adipocytes. The Cavin-3-dependent shedding mechanism appears to be an important process in adipocyte maturation, providing a potential therapeutic target for obesity-related disorders. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Open AccessArticle
A New Selective PPARγ Modulator Inhibits Triglycerides Accumulation during Murine Adipocytes’ and Human Adipose-Derived Mesenchymal Stem Cells Differentiation
Int. J. Mol. Sci. 2020, 21(12), 4415; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124415 - 21 Jun 2020
Viewed by 631
Abstract
Understanding the molecular basis of adipogenesis is vital to identify new therapeutic targets to improve anti-obesity drugs. The adipogenic process could be a new target in the management of this disease. Our aim was to evaluate the effect of GMG-43AC, a selective peroxisome [...] Read more.
Understanding the molecular basis of adipogenesis is vital to identify new therapeutic targets to improve anti-obesity drugs. The adipogenic process could be a new target in the management of this disease. Our aim was to evaluate the effect of GMG-43AC, a selective peroxisome proliferator-activated receptor γ (PPARγ) modulator, during adipose differentiation of murine pre-adipocytes and human Adipose Derived Stem Cells (hADSCs). We differentiated 3T3-L1 cells and primary hADSCs in the presence of various doses of GMG-43AC and evaluated the differentiation efficiency measuring lipid accumulation, the expression of specific differentiation markers and the quantification of accumulated triglycerides. The treatment with GMG-43AC is not toxic as shown by cell viability assessments after the treatments. Our findings demonstrate the inhibition of lipid accumulation and the significant decrease in the expression of adipocyte-specific genes, such as PPARγ, FABP-4, and leptin. This effect was long lasting, as the removal of GMG-43AC from culture medium did not allow the restoration of adipogenic process. The above actions were confirmed in hADSCs exposed to adipogenic stimuli. Together, these results indicate that GMG-43AC efficiently inhibits adipocytes differentiation in murine and human cells, suggesting its possible function in the reversal of adipogenesis and modulation of lipolysis. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Open AccessArticle
DHA Modulates Immune Response and Mitochondrial Function of Atlantic Salmon Adipocytes after LPS Treatment
Int. J. Mol. Sci. 2020, 21(11), 4101; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21114101 - 08 Jun 2020
Viewed by 734
Abstract
Adipocytes play a central role in overall energy homeostasis and are important contributors to the immune system. Fatty acids (FAs) act as signaling molecules capable to modulate adipocyte metabolism and functions. To identify the effects of two commonly used FAs in Atlantic salmon [...] Read more.
Adipocytes play a central role in overall energy homeostasis and are important contributors to the immune system. Fatty acids (FAs) act as signaling molecules capable to modulate adipocyte metabolism and functions. To identify the effects of two commonly used FAs in Atlantic salmon diets, primary adipocytes were cultured in the presence of oleic (OA) or docosahexaenoic (DHA) acid. DHA decreased adipocyte lipid droplet number and area compared to OA. The increase in lipid load in OA treated adipocytes was paralleled by an increase in iNOS activity and mitochondrial SOD2-GFP activity, which was probably directed to counteract increase in oxidative stress. Under lipopolysaccharide (LPS)-induced inflammation, DHA had a greater anti-inflammatory effect than OA, as evidenced by the higher SOD2 activity and the transcriptional regulation of antioxidant enzymes and pro- and anti-inflammatory markers. In addition, DHA maintained a healthy mitochondrial structure under induced inflammation while OA led to elongated mitochondria with a thin thread like structures in adipocytes exposed to LPS. Overall, DHA possess anti-inflammatory properties and protects Atlantic salmon against oxidative stress and limits lipid deposition. Furthermore, DHA plays a key role in protecting mitochondria shape and function. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Review

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Open AccessReview
The Impact of Single-Cell Genomics on Adipose Tissue Research
Int. J. Mol. Sci. 2020, 21(13), 4773; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21134773 - 05 Jul 2020
Cited by 3 | Viewed by 1179
Abstract
Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to [...] Read more.
Adipose tissue is an important regulator of whole-body metabolism and energy homeostasis. The unprecedented growth of obesity and metabolic disease worldwide has required paralleled advancements in research on this dynamic endocrine organ system. Single-cell RNA sequencing (scRNA-seq), a highly meticulous methodology used to dissect tissue heterogeneity through the transcriptional characterization of individual cells, is responsible for facilitating critical advancements in this area. The unique investigative capabilities achieved by the combination of nanotechnology, molecular biology, and informatics are expanding our understanding of adipose tissue’s composition and compartmentalized functional specialization, which underlie physiologic and pathogenic states, including adaptive thermogenesis, adipose tissue aging, and obesity. In this review, we will summarize the use of scRNA-seq and single-nuclei RNA-seq (snRNA-seq) in adipocyte biology and their applications to obesity and diabetes research in the hopes of increasing awareness of the capabilities of this technology and acting as a catalyst for its expanded use in further investigation. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Open AccessReview
Adipogenesis: A Complex Interplay of Multiple Molecular Determinants and Pathways
Int. J. Mol. Sci. 2020, 21(12), 4283; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21124283 - 16 Jun 2020
Cited by 11 | Viewed by 1122
Abstract
The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. [...] Read more.
The formation of adipocytes during embryogenesis has been largely understudied. However, preadipocytes appear to originate from multipotent mesenchymal stromal/stem cells which migrate from the mesoderm to their anatomical localization. Most studies on adipocyte formation (adipogenesis) have used preadipocytes derived from adult stem/stromal cells. Adipogenesis consists of two phases, namely commitment and terminal differentiation. This review discusses the role of signalling pathways, epigenetic modifiers, and transcription factors in preadipocyte commitment and differentiation into mature adipocytes, as well as limitations in our understanding of these processes. To date, a limited number of transcription factors, genes and signalling pathways have been described to regulate preadipocyte commitment. One reason could be that most studies on adipogenesis have used preadipocytes already committed to the adipogenic lineage, which are therefore not suitable for studying preadipocyte commitment. Conversely, over a dozen molecular players including transcription factors, genes, signalling pathways, epigenetic regulators, and microRNAs have been described to be involved in the differentiation of preadipocytes to adipocytes; however, only peroxisome proliferator-activated receptor gamma has proven to be clinically relevant. A detailed understanding of how the molecular players underpinning adipogenesis relate to adipose tissue function could provide new therapeutic approaches for addressing obesity without compromising adipose tissue function. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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Open AccessReview
The Role of Pref-1 during Adipogenic Differentiation: An Overview of Suggested Mechanisms
Int. J. Mol. Sci. 2020, 21(11), 4104; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms21114104 - 09 Jun 2020
Viewed by 723
Abstract
Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of adipocyte differentiation has predominantly been studied using [...] Read more.
Obesity contributes significantly to the global health burden. A better understanding of adipogenesis, the process of fat formation, may lead to the discovery of novel treatment strategies. However, it is of concern that the regulation of adipocyte differentiation has predominantly been studied using the murine 3T3-L1 preadipocyte cell line and murine experimental animal models. Translation of these findings to the human setting requires confirmation using experimental models of human origin. The ability of mesenchymal stromal/stem cells (MSCs) to differentiate into adipocytes is an attractive model to study adipogenesis in vitro. Differences in the ability of MSCs isolated from different sources to undergo adipogenic differentiation, may be useful in investigating elements responsible for regulating adipogenic differentiation potential. Genes involved may be divided into three broad categories: early, intermediate and late-stage regulators. Preadipocyte factor-1 (Pref-1) is an early negative regulator of adipogenic differentiation. In this review, we briefly discuss the adipogenic differentiation potential of MSCs derived from two different sources, namely adipose-derived stromal/stem cells (ASCs) and Wharton’s Jelly derived stromal/stem cells (WJSCs). We then discuss the function and suggested mechanisms of action of Pref-1 in regulating adipogenesis, as well as current findings regarding Pref-1’s role in human adipogenesis. Full article
(This article belongs to the Special Issue Adipogenesis and Adipose Tissue Metabolism 2.0)
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