Molecular Mechanisms of Adipose Organ Remodelling

A special issue of Cells (ISSN 2073-4409). This special issue belongs to the section "Tissues and Organs".

Deadline for manuscript submissions: closed (31 December 2023) | Viewed by 12294

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Guest Editor
Obesity Center, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy
Interests: diabetes; metabolic syndrome; nutrition; adipose organ; insulin resistance; metabolism; obesity; metabolic diseases; fat; metabolic endocrinology; breast; cancer; alveologenesis; pregnancy; lactation; postlactation
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Guest Editor
Dipartimento di Scienze Biomediche e Sanità Pubblica, Facolta di Medicina e Chirurgia, Università Politecnica delle Marche, Via Tronto, 10, 60126 Torrette di Ancona, Italy
Interests: adipose organ; cancer; heart; neurodegenerative diseases; regenerative medicine

Special Issue Information

Dear Colleagues,

Adipose tissues are organized to form a dissectible structure called the adipose organ. White adipose tissue (WAT) is formed by unilocular spherical cells containing a lipid vacuole that occupies most of the cell volume. This cell secretes fatty acids required for the 24 hours activity of the heart and all other tissues. Furthermore, it also produces two hormones that induce nutritional behaviours (search for food and food intake) and hepatic glucogenesis. Brown adipose tissue (BAT) is formed by smaller cells rich in mitochondria with several small lipid vacuoles. BAT burns lipids in special mitochondria provided with a unique protein (UCP1) responsible for the final result of its physiology: thermogenesis. Thus, although both tissues are formed by cells fulfilling the definition of adipocytes because of their abundant cytoplasmic lipids, they have different anatomies and different physiologies, which raises the question of their eventual cooperation. Usually, different tissues contained in organs cooperate for a finalistic purpose. Cold is the physiologic stimulus for BAT, and chronic cold also induces a browning of WAT, with the increment of thermogenesis. On the other hand, during a normal diet, WAT takes care of the metabolic needs of the organism, but in the case of a chronic positive energy balance, the organism exerts all of its ability to store precious calories, considering that a fasting period is not predictable; thus, in this particular condition, BAT convert into WAT to increase the body’s storing capacity. This theory offers an explanation as to why WAT and BAT are contained in the same organ, but implies a novel basic property for cells: the ability for a physiologic reversible gene reprogramming with a change of phenotype. We observed another striking example of cell conversion in the adipose organ during pregnancy and lactation. The alveolar part of mammary glands develops only in this period, in which the adipose component of the organ gradually disappears. Electron microscopy, lineage tracing, and explants data suggest that mammary alveolar cells are derived, at least in part, from the direct conversion of adipocytes.

Thus, the adipose organ is provided with a high level of plasticity, and a deeper knowledge of the molecular mechanisms responsible for its plasticity ,main purpose of this special issue, could open novel avenues for drug targets to treat obesity and related disorders, including breast cancer.

Prof. Dr. Saverio Cinti
Dr. Laura Graciotti
Guest Editors

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Keywords

  • adipose organ
  • white adipose tissue
  • brown adipose tissue
  • breast
  • alveologenesis
  • pregnancy
  • lactation
  • post-lactation
  • transdifferentiation
  • conversion
  • plasticity
  • remodelling
  • molecular mechanisms
  • obesity
  • diabetes
  • fat
  • endocrinology

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Published Papers (6 papers)

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Research

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18 pages, 3090 KiB  
Article
Adipo-Epithelial Transdifferentiation in In Vitro Models of the Mammary Gland
by Jessica Perugini, Arianna Smorlesi, Samantha Acciarini, Eleonora Mondini, Georgia Colleluori, Chiara Pirazzini, Katarzyna Malgorzata Kwiatkowska, Paolo Garagnani, Claudio Franceschi, Maria Cristina Zingaretti, Christian Dani, Antonio Giordano and Saverio Cinti
Cells 2024, 13(11), 943; https://doi.org/10.3390/cells13110943 - 30 May 2024
Cited by 1 | Viewed by 1010
Abstract
Subcutaneous adipocytes are crucial for mammary gland epithelial development during pregnancy. Our and others’ previous data have suggested that adipo-epithelial transdifferentiation could play a key role in the mammary gland alveolar development. In this study, we tested whether adipo-epithelial transdifferentiation occurs in vitro. [...] Read more.
Subcutaneous adipocytes are crucial for mammary gland epithelial development during pregnancy. Our and others’ previous data have suggested that adipo-epithelial transdifferentiation could play a key role in the mammary gland alveolar development. In this study, we tested whether adipo-epithelial transdifferentiation occurs in vitro. Data show that, under appropriate co-culture conditions with mammary epithelial organoids (MEOs), mature adipocytes lose their phenotype and acquire an epithelial one. Interestingly, even in the absence of MEOs, extracellular matrix and diffusible growth factors are able to promote adipo-epithelial transdifferentiation. Gene and protein expression studies indicate that transdifferentiating adipocytes exhibit some characteristics of milk-secreting alveolar glands, including significantly higher expression of milk proteins such as whey acidic protein and β-casein. Similar data were also obtained in cultured human multipotent adipose-derived stem cell adipocytes. A miRNA sequencing experiment on the supernatant highlighted mir200c, which has a well-established role in the mesenchymal–epithelial transition, as a potential player in this phenomenon. Collectively, our data show that adipo-epithelial transdifferentiation can be reproduced in in vitro models where this phenomenon can be investigated at the molecular level. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Adipose Organ Remodelling)
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14 pages, 2868 KiB  
Article
Effects of Fatty Acid Metabolites on Adipocytes Britening: Role of Thromboxane A2
by Cécilia Colson, Pierre-Louis Batrow, Sebastian Dieckmann, Laura Contu, Christian H. Roux, Laurence Balas, Claire Vigor, Baptiste Fourmaux, Nadine Gautier, Nathalie Rochet, Nathalie Bernoud-Hubac, Thierry Durand, Dominique Langin, Martin Klingenspor and Ez-Zoubir Amri
Cells 2023, 12(3), 446; https://doi.org/10.3390/cells12030446 - 30 Jan 2023
Cited by 3 | Viewed by 2401
Abstract
Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for [...] Read more.
Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis. The purpose of this work was to analyze the role of several lipokines in the control of brown/brite adipocyte formation. We used a validated human adipocyte model, human multipotent adipose-derived stem cell model (hMADS). In the absence of rosiglitazone, hMADS cells differentiate into white adipocytes, but convert into brite adipocytes upon rosiglitazone or prostacyclin 2 (PGI2) treatment. Gene expression was quantified using RT-qPCR and protein levels were assessed by Western blotting. We show here that lipokines such as 12,13-diHOME, 12-HEPE, 15dPGJ2 and 15dPGJ3 were not able to induce browning of white hMADS adipocytes. However, both fatty acid esters of hydroxy fatty acids (FAHFAs), 9-PAHPA and 9-PAHSA potentiated brown key marker UCP1 mRNA levels. Interestingly, CTA2, the stable analog of thromboxane A2 (TXA2), but not its inactive metabolite TXB2, inhibited the rosiglitazone and PGI2-induced browning of hMADS adipocytes. These results pinpoint TXA2 as a lipokine inhibiting brown adipocyte formation that is antagonized by PGI2. Our data open new horizons in the development of potential therapies based on the control of thromboxane A2/prostacyclin balance to combat obesity and associated metabolic disorders. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Adipose Organ Remodelling)
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Review

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34 pages, 1518 KiB  
Review
Early Life Programming of Adipose Tissue Remodeling and Browning Capacity by Micronutrients and Bioactive Compounds as a Potential Anti-Obesity Strategy
by M. Luisa Bonet, Joan Ribot, Juana Sánchez, Andreu Palou and Catalina Picó
Cells 2024, 13(10), 870; https://doi.org/10.3390/cells13100870 - 18 May 2024
Viewed by 1745
Abstract
The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) [...] Read more.
The early stages of life, especially the period from conception to two years, are crucial for shaping metabolic health and the risk of obesity in adulthood. Adipose tissue (AT) plays a crucial role in regulating energy homeostasis and metabolism, and brown AT (BAT) and the browning of white AT (WAT) are promising targets for combating weight gain. Nutritional factors during prenatal and early postnatal stages can influence the development of AT, affecting the likelihood of obesity later on. This narrative review focuses on the nutritional programming of AT features. Research conducted across various animal models with diverse interventions has provided insights into the effects of specific compounds on AT development and function, influencing the development of crucial structures and neuroendocrine circuits responsible for energy balance. The hormone leptin has been identified as an essential nutrient during lactation for healthy metabolic programming against obesity development in adults. Studies have also highlighted that maternal supplementation with polyunsaturated fatty acids (PUFAs), vitamin A, nicotinamide riboside, and polyphenols during pregnancy and lactation, as well as offspring supplementation with myo-inositol, vitamin A, nicotinamide riboside, and resveratrol during the suckling period, can impact AT features and long-term health outcomes and help understand predisposition to obesity later in life. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Adipose Organ Remodelling)
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39 pages, 5797 KiB  
Review
Impaired Remodeling of White Adipose Tissue in Obesity and Aging: From Defective Adipogenesis to Adipose Organ Dysfunction
by Carla Iacobini, Martina Vitale, Jonida Haxhi, Stefano Menini and Giuseppe Pugliese
Cells 2024, 13(9), 763; https://doi.org/10.3390/cells13090763 - 30 Apr 2024
Cited by 3 | Viewed by 2043
Abstract
The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy surplus, the subcutaneous white adipose tissue (WAT) is capable of expanding through the enlargement of existing adipocytes (hypertrophy), followed by [...] Read more.
The adipose organ adapts and responds to internal and environmental stimuli by remodeling both its cellular and extracellular components. Under conditions of energy surplus, the subcutaneous white adipose tissue (WAT) is capable of expanding through the enlargement of existing adipocytes (hypertrophy), followed by de novo adipogenesis (hyperplasia), which is impaired in hypertrophic obesity. However, an impaired hyperplastic response may result from various defects in adipogenesis, leading to different WAT features and metabolic consequences, as discussed here by reviewing the results of the studies in animal models with either overexpression or knockdown of the main molecular regulators of the two steps of the adipogenesis process. Moreover, impaired WAT remodeling with aging has been associated with various age-related conditions and reduced lifespan expectancy. Here, we delve into the latest advancements in comprehending the molecular and cellular processes underlying age-related changes in WAT function, their involvement in common aging pathologies, and their potential as therapeutic targets to influence both the health of elderly people and longevity. Overall, this review aims to encourage research on the mechanisms of WAT maladaptation common to conditions of both excessive and insufficient fat tissue. The goal is to devise adipocyte-targeted therapies that are effective against both obesity- and age-related disorders. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Adipose Organ Remodelling)
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13 pages, 4832 KiB  
Review
Bone Marrow Adipose Tissue
by Elena Marinelli Busilacchi, Erika Morsia and Antonella Poloni
Cells 2024, 13(9), 724; https://doi.org/10.3390/cells13090724 - 23 Apr 2024
Cited by 1 | Viewed by 2985
Abstract
Bone marrow (BM) acts as a dynamic organ within the bone cavity, responsible for hematopoiesis, skeletal remodeling, and immune system control. Bone marrow adipose tissue (BMAT) was long simply considered a filler of space, but now it is known that it instead constitutes [...] Read more.
Bone marrow (BM) acts as a dynamic organ within the bone cavity, responsible for hematopoiesis, skeletal remodeling, and immune system control. Bone marrow adipose tissue (BMAT) was long simply considered a filler of space, but now it is known that it instead constitutes an essential element of the BM microenvironment that participates in homeostasis, influences bone health and bone remodeling, alters hematopoietic stem cell functions, contributes to the commitment of mesenchymal stem cells, provides effects to immune homeostasis and defense against infections, and participates in energy metabolism and inflammation. BMAT has emerged as a significant contributor to the development and progression of various diseases, shedding light on its complex relationship with health. Notably, BMAT has been implicated in metabolic disorders, hematological malignancies, and skeletal conditions. BMAT has been shown to support the proliferation of tumor cells in acute myeloid leukemia and niche adipocytes have been found to protect cancer cells against chemotherapy, contributing to treatment resistance. Moreover, BMAT’s impact on bone density and remodeling can lead to conditions like osteoporosis, where high levels of BMAT are inversely correlated with bone mineral density, increasing the risk of fractures. BMAT has also been associated with diabetes, obesity, and anorexia nervosa, with varying effects on individuals depending on their weight and health status. Understanding the interaction between adipocytes and different diseases may lead to new therapeutic strategies. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Adipose Organ Remodelling)
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Other

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12 pages, 1413 KiB  
Commentary
Overactivation of the Endocannabinoid System in Adolescence Disrupts Adult Adipose Organ Function in Mice
by Kwang-Mook Jung, Lin Lin and Daniele Piomelli
Cells 2024, 13(5), 461; https://doi.org/10.3390/cells13050461 - 6 Mar 2024
Viewed by 1426
Abstract
Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don’t. Two explanations have been proposed for this paradoxical finding. One posits that Δ9-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid [...] Read more.
Cannabis use stimulates calorie intake, but epidemiological studies show that people who regularly use it are leaner than those who don’t. Two explanations have been proposed for this paradoxical finding. One posits that Δ9-tetrahydrocannabinol (THC) in cannabis desensitizes adipose CB1 cannabinoid receptors, stopping their stimulating effects on lipogenesis and adipogenesis. Another explanation is that THC exposure in adolescence, when habitual cannabis use typically starts, produces lasting changes in the developing adipose organ, which impacts adult systemic energy use. Here, we consider these possibilities in the light of a study which showed that daily THC administration in adolescent mice produces an adult metabolic phenotype characterized by reduced fat mass, partial resistance to obesity and dyslipidemia, and impaired thermogenesis and lipolysis. The phenotype, whose development requires activation of CB1 receptors in differentiated adipocytes, is associated with overexpression of myocyte proteins in the adipose organ with unchanged CB1 expression. We propose that adolescent exposure to THC causes lasting adipocyte dysfunction and the consequent emergence of a metabolic state that only superficially resembles healthy leanness. A corollary of this hypothesis, which should be addressed in future studies, is that CB1 receptors and their endocannabinoid ligands may contribute to the maintenance of adipocyte differentiation during adolescence. Full article
(This article belongs to the Special Issue Molecular Mechanisms of Adipose Organ Remodelling)
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