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Role of Adipose Organ in Metabolism and Disease

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A special issue of Biomedicines (ISSN 2227-9059). This special issue belongs to the section "Molecular and Translational Medicine".

Deadline for manuscript submissions: closed (30 September 2023) | Viewed by 16962

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Special Issue Editor

Prof. Dr. Saverio Cinti

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Scientific Director of Center of Obesity, Department of Experimental and Clinical Medicine, Università Politecnica delle Marche, Ancona, Italy
Interests: nutrition; metabolism; insulin resistance; diabetes; metabolic diseases; metabolic syndrome; obesity; adipose tissue; adipogenesis; ultrastructure; diabetes mellitus type 2; adipocytes; leptin; adipose-derived stem cells; white adipose tissue; brown adipose tissue
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Dear Colleagues,

Obesity is the fifth leading cause of death worldwide. At the end of 18^th Century, the Italian anatomist Gian Battista Morgagni defined illness as a condition in which a pathologic organ can be demonstrated. White adipose tissue of obese animals and humans is inflamed by a chronic low-grade inflammation sustained mainly by macrophages. These cells are scavengers attracted in the obese adipose tissues by remnants derived from death of hypertrophic white adipocytes.

Together with white adipocytes that store lipids for metabolic needs, there are also brown adipocytes with different physiology: they burn lipids for thermogenesis.

Both adipocytes are contained together into a dissectible structure fulfilling the definition of organ: dissectible structure formed at least by two different tissues cooperating each other. The cooperation between white and brown is reached by their ability to convert each other: during chronic cold exposure white convert to brown in order to help thermogenesis, when the energy balance is positive brown convert to white to increase the storage capacity. Thus, obese animals and humans have a pathologic organ and obesity is an illness.

In this issue the human adipose organ and its implication for obesity is described. Several metabolic and pathologic aspects deriving and connected to this new concept are also described in this issue.

Prof. Dr. Saverio Cinti
Guest Editor

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Keywords

adipose organ
white adipocytes
brown adipocytes
subcutaneous adipose tissue
visceral adipose tissue
inflammation
metabolism
pathology

Published Papers (5 papers)

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Research

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16 pages, 3791 KiB

Open AccessArticle

Uncoupling Lipid Synthesis from Adipocyte Development

by Qianfen Wan, Carmen Calhoun, Tarik Zahr and Li Qiang

Biomedicines 2023, 11(4), 1132; https://doi.org/10.3390/biomedicines11041132 - 9 Apr 2023

Cited by 3 | Viewed by 1772

Abstract

Obesity results from the expansion of adipose tissue, a versatile tissue regulating energy homeostasis, adipokine secretion, thermogenesis, and inflammation. The primary function of adipocytes is thought to be lipid storage through lipid synthesis, which is presumably intertwined with adipogenesis. However, during prolonged fasting, adipocytes are depleted of lipid droplets yet retain endocrine function and an instant response to nutrients. This observation led us to question whether lipid synthesis and storage can be uncoupled from adipogenesis and adipocyte function. By inhibiting key enzymes in the lipid synthesis pathway during adipocyte development, we demonstrated that a basal level of lipid synthesis is essential for adipogenesis initiation but not for maturation and maintenance of adipocyte identity. Furthermore, inducing dedifferentiation of mature adipocytes abrogated adipocyte identity but not lipid storage. These findings suggest that lipid synthesis and storage are not the defining features of adipocytes and raise the possibility of uncoupling lipid synthesis from adipocyte development to achieve smaller and healthier adipocytes for the treatment of obesity and related disorders. Full article

(This article belongs to the Special Issue Role of Adipose Organ in Metabolism and Disease)

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18 pages, 10371 KiB

Open AccessArticle

The Adipose Organ Is a Unitary Structure in Mice and Humans

by A. Giordano, F. Cinti, R. Canese, G. Carpinelli, G. Colleluori, A. Di Vincenzo, G. Palombelli, I. Severi, M. Moretti, C. Redaelli, J. Partridge, M. C. Zingaretti, A. Agostini, F. Sternardi, A. Giovagnoni, S. Castorina and S. Cinti

Biomedicines 2022, 10(9), 2275; https://doi.org/10.3390/biomedicines10092275 - 14 Sep 2022

Cited by 12 | Viewed by 4955

Abstract

Obesity is the fifth leading cause of death worldwide. In mice and humans with obesity, the adipose organ undergoes remarkable morpho-functional alterations. The comprehension of the adipose organ function and organization is of paramount importance to understand its pathology and formulate future therapeutic strategies. In the present study, we performed anatomical dissections, magnetic resonance imaging, computed axial tomography and histological and immunohistochemical assessments of humans and mouse adipose tissues. We demonstrate that most of the two types of adipose tissues (white, WAT and brown, BAT) form a large unitary structure fulfilling all the requirements necessary to be considered as a true organ in both species. A detailed analysis of the gross anatomy of mouse adipose organs in different pathophysiological conditions (normal, cold, pregnancy, obesity) shows that the organ consists of a unitary structure composed of different tissues: WAT, BAT, and glands (pregnancy). Data from autoptic dissection of 8 cadavers, 2 females and 6 males (Age: 37.5 ± 9.7, BMI: 23 ± 2.7 kg/m²) and from detailed digital dissection of 4 digitalized cadavers, 2 females and 2 males (Age: 39 ± 14.2 years, BMI: 22.8 ± 4.3 kg/m²) confirmed the mixed (WAT and BAT) composition and the unitary structure of the adipose organ also in humans. Considering the remarkable endocrine roles of WAT and BAT, the definition of the endocrine adipose organ would be even more appropriate in mice and humans. Full article

(This article belongs to the Special Issue Role of Adipose Organ in Metabolism and Disease)

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Review

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25 pages, 4816 KiB

Open AccessReview

Obesity, the Adipose Organ and Cancer in Humans: Association or Causation?

by Elisabetta Trevellin, Silvia Bettini, Anna Pilatone, Roberto Vettor and Gabriella Milan

Biomedicines 2023, 11(5), 1319; https://doi.org/10.3390/biomedicines11051319 - 28 Apr 2023

Cited by 4 | Viewed by 2441

Abstract

Epidemiological observations, experimental studies and clinical data show that obesity is associated with a higher risk of developing different types of cancer; however, proof of a cause–effect relationship that meets the causality criteria is still lacking. Several data suggest that the adipose organ could be the protagonist in this crosstalk. In particular, the adipose tissue (AT) alterations occurring in obesity parallel some tumour behaviours, such as their theoretically unlimited expandability, infiltration capacity, angiogenesis regulation, local and systemic inflammation and changes to the immunometabolism and secretome. Moreover, AT and cancer share similar morpho-functional units which regulate tissue expansion: the adiponiche and tumour-niche, respectively. Through direct and indirect interactions involving different cellular types and molecular mechanisms, the obesity-altered adiponiche contributes to cancer development, progression, metastasis and chemoresistance. Moreover, modifications to the gut microbiome and circadian rhythm disruption also play important roles. Clinical studies clearly demonstrate that weight loss is associated with a decreased risk of developing obesity-related cancers, matching the reverse-causality criteria and providing a causality correlation between the two variables. Here, we provide an overview of the methodological, epidemiological and pathophysiological aspects, with a special focus on clinical implications for cancer risk and prognosis and potential therapeutic interventions. Full article

(This article belongs to the Special Issue Role of Adipose Organ in Metabolism and Disease)

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19 pages, 554 KiB

Open AccessReview

GPCR in Adipose Tissue Function—Focus on Lipolysis

by Davide Malfacini and Alexander Pfeifer

Biomedicines 2023, 11(2), 588; https://doi.org/10.3390/biomedicines11020588 - 16 Feb 2023

Cited by 8 | Viewed by 5120

Abstract

Adipose tissue can be divided anatomically, histologically, and functionally into two major entities white and brown adipose tissues (WAT and BAT, respectively). WAT is the primary energy depot, storing most of the bioavailable triacylglycerol molecules of the body, whereas BAT is designed for dissipating energy in the form of heat, a process also known as non-shivering thermogenesis as a defense against a cold environment. Importantly, BAT-dependent energy dissipation directly correlates with cardiometabolic health and has been postulated as an intriguing target for anti-obesity therapies. In general, adipose tissue (AT) lipid content is defined by lipid uptake and lipogenesis on one side, and, on the other side, it is defined by the breakdown of lipids and the release of fatty acids by lipolysis. The equilibrium between lipogenesis and lipolysis is important for adipocyte and general metabolic homeostasis. Overloading adipocytes with lipids causes cell stress, leading to the recruitment of immune cells and adipose tissue inflammation, which can affect the whole organism (metaflammation). The most important consequence of energy and lipid overload is obesity and associated pathophysiologies, including insulin resistance, type 2 diabetes, and cardiovascular disease. The fate of lipolysis products (fatty acids and glycerol) largely differs between AT: WAT releases fatty acids into the blood to deliver energy to other tissues (e.g., muscle). Activation of BAT, instead, liberates fatty acids that are used within brown adipocyte mitochondria for thermogenesis. The enzymes involved in lipolysis are tightly regulated by the second messenger cyclic adenosine monophosphate (cAMP), which is activated or inhibited by G protein-coupled receptors (GPCRs) that interact with heterotrimeric G proteins (G proteins). Thus, GPCRs are the upstream regulators of the equilibrium between lipogenesis and lipolysis. Moreover, GPCRs are of special pharmacological interest because about one third of the approved drugs target GPCRs. Here, we will discuss the effects of some of most studied as well as “novel” GPCRs and their ligands. We will review different facets of in vitro, ex vivo, and in vivo studies, obtained with both pharmacological and genetic approaches. Finally, we will report some possible therapeutic strategies to treat obesity employing GPCRs as primary target. Full article

(This article belongs to the Special Issue Role of Adipose Organ in Metabolism and Disease)

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13 pages, 787 KiB

Open AccessReview

The Sexual Dimorphism of Human Adipose Depots

by Nathalie Boulet, Anais Briot, Jean Galitzky and Anne Bouloumié

Biomedicines 2022, 10(10), 2615; https://doi.org/10.3390/biomedicines10102615 - 18 Oct 2022

Cited by 8 | Viewed by 1917

Abstract

The amount and the distribution of body fat exhibit trajectories that are sex- and human species-specific and both are determinants for health. The enhanced accumulation of fat in the truncal part of the body as a risk factor for cardiovascular and metabolic diseases is well supported by epidemiological studies. In addition, a possible independent protective role of the gluteofemoral fat compartment and of the brown adipose tissue is emerging. The present narrative review summarizes the current knowledge on sexual dimorphism in fat depot amount and repartition and consequences on cardiometabolic and reproductive health. The drivers of the sex differences and fat depot repartition, considered to be the results of complex interactions between sex determination pathways determined by the sex chromosome composition, genetic variability, sex hormones and the environment, are discussed. Finally, the inter- and intra-depot heterogeneity in adipocytes and progenitors, emphasized recently by unbiased large-scale approaches, is highlighted. Full article

(This article belongs to the Special Issue Role of Adipose Organ in Metabolism and Disease)

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