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Adipose Tissue and Gene Expression
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Adipose Tissue and Gene Expression

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

Deadline for manuscript submissions: 20 December 2024 | Viewed by 9189

Special Issue Editors

Dr. Margherita Maffei

E-Mail Website
Guest Editor
Institute of Clinical Physiology, National Research Council (CNR), 56124 Pisa, Italy
Interests: adipose tissue; energy balance; lipodystrophy; micro-RNAs
Dr. Gaia Scabia

E-Mail Website
Guest Editor
Institute of Clinical Physiology, National Research Council (CNR), 56124 Pisa, Italy
Interests: adipose tissue; energy balance; lipodystrophy; micro-RNAs

Special Issue Information

Dear Colleagues,

The past 30 years marked a radical change in the definition of adipose tissue, now not only a reservoir of energy (white adipose tissue, WAT) or a heat producer for adaptive thermogenesis (brown adipose tissue, BAT), but also an endocrine organ capable of extensive interactions with other systems by means of hormones, cytokines, adipokines, and metabolites, able to control several key physiological functions: reproduction, bone homeostasis, the immune system, and energy balance, among others.

WAT and BAT are able to respond and adapt to external conditions, including changes in the energy and metabolic state of an organism, environmental stimuli, or insults; gene expression changes underlie this adaptive capacity. Understanding the fat-depot-specific variations in gene expression profiles helps to clarify pathological mechanisms not yet uncovered; moreover, it may provide potential biomarkers as well as therapeutic targets to be developed in future research.

This Special Issue aims to collect new insights into the gene expression regulation in WAT and BAT underlying dysfunctions or alterations due to metabolic challenges, such as obesity or diabetes, nutritional stimuli, aging, and responses to environmental cues.

Of particular interest will be those papers focused on the study of adipose organ (AO) alterations in gene expression as a consequence of lipodystrophy, the presence of lipomas, multiple symmetric lipomatosis, and other rare pathological conditions that alter fat distribution. Indeed, acquiring knowledge on the etiopathogenesis of these rare diseases constitutes a yet-uncovered need in the literature.

micro-RNAs were recently found to play a central role in regulating gene expression in AO, and they were implied in adipogenesis as well as mature adipocyte function. Articles reporting novel information on this matter are welcome.

Dr. Margherita Maffei
Dr. Gaia Scabia
Guest Editors

Manuscript Submission Information

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Keywords

  • adipose tissue dysfunction
  • lipomatosis
  • fat distribution
  • lipodystrophy
  • micro-RNA
  • dysmetabolism
  • diet
  • inflammation
  • rare disease
  • transcription

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Published Papers (6 papers)

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Research

16 pages, 2741 KiB  
Article
Transcriptional Dynamics and Key Regulators of Adipogenesis in Mouse Embryonic Stem Cells: Insights from Robust Rank Aggregation Analysis
by Mouza Alzaabi, Mariam Khalili, Mehar Sultana and Mohamed Al-Sayegh
Int. J. Mol. Sci. 2024, 25(17), 9154; https://doi.org/10.3390/ijms25179154 - 23 Aug 2024
Viewed by 769
Abstract
Embryonic stem cells are crucial for studying developmental biology due to their self-renewal and pluripotency capabilities. This research investigates the differentiation of mouse ESCs into adipocytes, offering insights into obesity and metabolic disorders. Using a monolayer differentiation approach over 30 days, lipid accumulation [...] Read more.
Embryonic stem cells are crucial for studying developmental biology due to their self-renewal and pluripotency capabilities. This research investigates the differentiation of mouse ESCs into adipocytes, offering insights into obesity and metabolic disorders. Using a monolayer differentiation approach over 30 days, lipid accumulation and adipogenic markers, such as Cebpb, Pparg, and Fabp4, confirmed successful differentiation. RNA sequencing revealed extensive transcriptional changes, with over 15,000 differentially expressed genes linked to transcription regulation, cell cycle, and DNA repair. This study utilized Robust Rank Aggregation to identify critical regulatory genes like PPARG, CEBPA, and EP300. Network analysis further highlighted Atf5, Ccnd1, and Nr4a1 as potential key players in adipogenesis and its mature state, validated through RT-PCR. While key adipogenic factors showed plateaued expression levels, suggesting early differentiation events, this study underscores the value of ESCs in modeling adipogenesis. These findings contribute to our understanding of adipocyte differentiation and have significant implications for therapeutic strategies targeting metabolic diseases. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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20 pages, 5762 KiB  
Article
Domestication Gene Mlx and Its Partner Mondo Are Involved in Controlling the Larval Body Size and Cocoon Shell Weight of Bombyx mori
by Xiaoxuan Qin, Liang Jiang, Ping Zhao, Ying Lin, Yi Zhang and Qingyou Xia
Int. J. Mol. Sci. 2024, 25(6), 3427; https://doi.org/10.3390/ijms25063427 - 18 Mar 2024
Viewed by 1247
Abstract
Bombyx mori was domesticated from Bombyx mandarina. The long-term domestication of the silkworm has brought about many remarkable changes to its body size and cocoon shell weight. However, the molecular mechanism underlying the improvement in the economic characteristics of this species during [...] Read more.
Bombyx mori was domesticated from Bombyx mandarina. The long-term domestication of the silkworm has brought about many remarkable changes to its body size and cocoon shell weight. However, the molecular mechanism underlying the improvement in the economic characteristics of this species during domestication remains unclear. In this study, we found that a transposable element (TE)—Bm1—was present in the upstream regulatory region of the Mlx (Max-like protein X) gene in wild silkworms but not in all domesticated silkworms. The absence of Bm1 caused an increase in the promoter activity and mRNA content of Mlx. Mlx and its partner Mondo belong to the bHLHZ transcription factors family and regulate nutrient metabolism. RNAi of Mlx and Mondo decreased the expression and promoter activity of glucose metabolism-related genes (trehalose transport (Tret), phosphofructokinase (PFK), and pyruvate kinase (PK)), lipogenic genes (Acetyl-CoA carboxylase (ACC) and fatty acid synthase (FAS)), and glutamine synthesis gene (Glutamine synthase 2, (GS2)). Furthermore, the transgenic overexpression of Mlx and Mondo in the fat body of silkworms increased the larval body size, cocoon shell weight, and egg number, but the silencing of the two genes resulted in the opposite phenotypes. Our results reveal the molecular mechanism of Mlx selection during domestication and its successful use in the molecular breeding of Bombyx mori. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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14 pages, 8832 KiB  
Article
Let-7a-5p Regulates Animal Lipid Accumulation by Targeting Srebf2 and Thbs1 Signaling
by Jiahao Shao, Genglong Jiang, Yanhong Li, Meigui Wang, Tao Tang, Jie Wang, Xianbo Jia and Songjia Lai
Int. J. Mol. Sci. 2024, 25(2), 894; https://doi.org/10.3390/ijms25020894 - 11 Jan 2024
Cited by 1 | Viewed by 1356
Abstract
Recently, the trend of obesity is becoming increasingly prevalent, and the underlying pathogenesis of obesity is complex and needs to be researched further. In this study, we report a decreased expression of let-7a-5p in the white adipose tissue (WAT) of animals with obesity. [...] Read more.
Recently, the trend of obesity is becoming increasingly prevalent, and the underlying pathogenesis of obesity is complex and needs to be researched further. In this study, we report a decreased expression of let-7a-5p in the white adipose tissue (WAT) of animals with obesity. Using the RNA oligo, let-7a-5p over-expression or suppression–expression is achieved, impacting the proliferation and differentiation of preadipocytes in vitro. Srebf2 mechanistically interacts with the metabolic effect of let-7a-5p and participates in lipid accumulation by regulating Srebf2 downstream signaling. Moreover, let-7a-5p binds to Thbs1 to interact with the PI3K-AKT-mTOR pathway, down-regulating the phosphorylation levels of AKT, mTOR, and S6K1 to decrease lipid accumulation. In conclusion, our study highlights the physiological significance of let-7a-5p in lipid accumulation and suggests that the let-7a-5p/Srebf2 and let-7a-5p/Thbs1/PI3K-AKT-mTOR axes may represent potential mechanisms for controlling lipid accumulation in obesity. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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14 pages, 2979 KiB  
Article
miR-889-3p Facilitates the Browning Process of White Adipocyte Precursors by Targeting the SON Gene
by Wenqiang Sun, Xiaoxiao Zhang, Xue Bai, Kun Du, Li Chen, Haoding Wang, Xianbo Jia and Songjia Lai
Int. J. Mol. Sci. 2023, 24(24), 17580; https://doi.org/10.3390/ijms242417580 - 17 Dec 2023
Viewed by 1337
Abstract
It is well-established that beige/brown adipose tissue can dissipate stored energy through thermogenesis; hence, the browning of white adipocytes (WAT) has garnered significant interest in contemporary research. Our preceding investigations have identified a marked downregulation of miR-889-3p concurrent with the natural maturation of [...] Read more.
It is well-established that beige/brown adipose tissue can dissipate stored energy through thermogenesis; hence, the browning of white adipocytes (WAT) has garnered significant interest in contemporary research. Our preceding investigations have identified a marked downregulation of miR-889-3p concurrent with the natural maturation of brown adipose tissue. However, the specific role and underlying molecular mechanisms of miR-889-3p in the browning process of white adipose tissue warrant further elucidation. In this research, we initially delved into the potential role of miR-889-3p in preadipocyte growth via flow cytometry and CCK-8 assay, revealing that miR-889-3p can stimulate preadipocyte growth. To validate the potential contribution of miR-889-3p in the browning process of white adipose tissue, we established an in vitro rabbit white adipocyte browning induction, which exhibited a significant upregulation of miR-889-3p during the browning process. RT-qPCR and Western blot analysis indicated that miR-889-3p overexpression significantly amplified the mRNA levels of UCP1, PRDM16, and CIDEA, as well as UCP1 protein levels. Furthermore, miR-889-3p overexpression fostered intracellular triglyceride accumulation. Conversely, the downregulation of miR-889-3p hindered the browning of rabbit preadipocytes. Subsequently, based on target gene prediction and luciferase reporter gene determination, we demonstrated that miR-889-3p directly targets the 3′-UTR region of SON. Lastly, we observed that inhibiting SON could facilitate the browning of rabbit preadipocytes. In conclusion, our findings suggest that miR-889-3p facilitates the browning process of white adipocyte precursors by specifically targeting the SON gene. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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16 pages, 2604 KiB  
Article
LRP10, PGK1 and RPLP0: Best Reference Genes in Periprostatic Adipose Tissue under Obesity and Prostate Cancer Conditions
by Jesús M. Pérez-Gómez, Francisco Porcel-Pastrana, Marina De La Luz-Borrero, Antonio J. Montero-Hidalgo, Enrique Gómez-Gómez, Aura D. Herrera-Martínez, Rocío Guzmán-Ruiz, María M. Malagón, Manuel D. Gahete and Raúl M. Luque
Int. J. Mol. Sci. 2023, 24(20), 15140; https://doi.org/10.3390/ijms242015140 - 13 Oct 2023
Cited by 4 | Viewed by 1920
Abstract
Obesity (OB) is a metabolic disorder characterized by adipose tissue dysfunction that has emerged as a health problem of epidemic proportions in recent decades. OB is associated with multiple comorbidities, including some types of cancers. Specifically, prostate cancer (PCa) has been postulated as [...] Read more.
Obesity (OB) is a metabolic disorder characterized by adipose tissue dysfunction that has emerged as a health problem of epidemic proportions in recent decades. OB is associated with multiple comorbidities, including some types of cancers. Specifically, prostate cancer (PCa) has been postulated as one of the tumors that could have a causal relationship with OB. Particularly, a specialized adipose tissue (AT) depot known as periprostatic adipose tissue (PPAT) has gained increasing attention over the last few years as it could be a key player in the pathophysiological interaction between PCa and OB. However, to date, no studies have defined the most appropriate internal reference genes (IRGs) to be used in gene expression studies in this AT depot. In this work, two independent cohorts of PPAT samples (n = 20/n = 48) were used to assess the validity of a battery of 15 literature-selected IRGs using two widely used techniques (reverse transcription quantitative PCR [RT-qPCR] and microfluidic-based qPCR array). For this purpose, ΔCt method, GeNorm (v3.5), BestKeeper (v1.0), NormFinder (v.20.0), and RefFinder software were employed to assess the overall trends of our analyses. LRP10, PGK1, and RPLP0 were identified as the best IRGs to be used for gene expression studies in human PPATs, specifically when considering PCa and OB conditions. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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24 pages, 3693 KiB  
Article
Regulation of Human Sortilin Alternative Splicing by Glucagon-like Peptide-1 (GLP1) in Adipocytes
by Ashley Lui, Rekha S. Patel, Meredith Krause-Hauch, Robert P. Sparks and Niketa A. Patel
Int. J. Mol. Sci. 2023, 24(18), 14324; https://doi.org/10.3390/ijms241814324 - 20 Sep 2023
Viewed by 1780
Abstract
Type 2 diabetes mellitus is a chronic metabolic disease with no cure. Adipose tissue is a major site of systemic insulin resistance. Sortilin is a central component of the glucose transporter -Glut4 storage vesicles (GSV) which translocate to the plasma membrane to uptake [...] Read more.
Type 2 diabetes mellitus is a chronic metabolic disease with no cure. Adipose tissue is a major site of systemic insulin resistance. Sortilin is a central component of the glucose transporter -Glut4 storage vesicles (GSV) which translocate to the plasma membrane to uptake glucose from circulation. Here, using human adipocytes we demonstrate the presence of the alternatively spliced, truncated sortilin variant (Sort_T) whose expression is significantly increased in diabetic adipose tissue. Artificial-intelligence-based modeling, molecular dynamics, intrinsically disordered region analysis, and co-immunoprecipitation demonstrated association of Sort_T with Glut4 and decreased glucose uptake in adipocytes. The results show that glucagon-like peptide-1 (GLP1) hormone decreases Sort_T. We deciphered the molecular mechanism underlying GLP1 regulation of alternative splicing of human sortilin. Using splicing minigenes and RNA-immunoprecipitation assays, the results show that GLP1 regulates Sort_T alternative splicing via the splice factor, TRA2B. We demonstrate that targeted antisense oligonucleotide morpholinos reduces Sort_T levels and improves glucose uptake in diabetic adipocytes. Thus, we demonstrate that GLP1 regulates alternative splicing of sortilin in human diabetic adipocytes. Full article
(This article belongs to the Special Issue Adipose Tissue and Gene Expression)
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