Adipose tissue: colors, depots and functions

Obesity is a chronic disease characterized by excessive accumulation of adipose tissue. The prevalence of obesity and associated diseases has prompted researchers to expand the study of the biology of adipose tissue. New technologies have significantly expanded the understanding of adipogenesis mechanisms, various aspects of lipid and glucose metabolism, as well as the paracrine and endocrine functions of adipose tissue. Adipose tissue is a complex, heterogeneous endocrine organ. The existence of several shades of adipocytes demonstrates their morphological and functional heterogeneity. The main function of white adipose tissue is to store energy. Brown and white adipocytes perform a predominantly thermogenic function. Bone marrow (yellow) adipose tissue regulates the processes of bone remodeling and hematopoiesis. Pink adipocytes are formed during pregnancy and satisfy the energy needs of the offspring. The study of the biology of adipose tissue is crucial to understanding the pathophysiology of obesity and determining its molecular relationships with type 2 diabetes as well as cardiovascular and oncological diseases. The review presents current literature data on the origin, adipogenesis, and functional properties of adipose tissue depending on its cellular composition and localization. It outlines the nature of changes in adipose tissue in obesity and the clinical significance and therapeutic potential of various adipose tissue depots.

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Deciphering White Adipose Tissue Heterogeneity

Biology ◽

10.3390/biology8020023 ◽

2019 ◽

Vol 8 (2) ◽

pp. 23 ◽

Cited By ~ 19

Author(s):

Quyen Luong ◽

Jun Huang ◽

Kevin Y. Lee

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Lineage Tracing ◽

The Body ◽

Functional Heterogeneity ◽

Tissue Heterogeneity ◽

Adipose Tissue Depots ◽

White Adipocytes ◽

Increased Risk ◽

Beige Adipocytes

Adipose tissue not only stores energy, but also controls metabolism through secretion of hormones, cytokines, proteins, and microRNAs that affect the function of cells and tissues throughout the body. Adipose tissue is organized into discrete depots throughout the body, and these depots are differentially associated with insulin resistance and increased risk of metabolic disease. In addition to energy-dissipating brown and beige adipocytes, recent lineage tracing studies have demonstrated that individual adipose depots are composed of white adipocytes that are derived from distinct precursor populations, giving rise to distinct subpopulations of energy-storing white adipocytes. In this review, we discuss this developmental and functional heterogeneity of white adipocytes both between and within adipose depots. In particular, we will highlight findings from our recent manuscript in which we find and characterize three major subtypes of white adipocytes. We will discuss these data relating to the differences between subcutaneous and visceral white adipose tissue and in relationship to previous work deciphering adipocyte heterogeneity within adipose tissue depots. Finally, we will discuss the possible implications of adipocyte heterogeneity may have for the understanding of lipodystrophies.

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The dual nature of obesity in metabolic programming: quantity versus quality of adipose tissue

Clinical Science ◽

10.1042/cs20201028 ◽

2020 ◽

Vol 134 (18) ◽

pp. 2447-2451

Author(s):

Anissa Viveiros ◽

Gavin Y. Oudit

Keyword(s):

Adipose Tissue ◽

Environmental Factors ◽

Maternal Obesity ◽

Metabolic Programming ◽

Dual Nature ◽

Prevalence Of Obesity ◽

Adipose Tissue Volume ◽

Males And Females ◽

Metabolically Healthy

Abstract The global prevalence of obesity has been rising at an alarming rate, accompanied by an increase in both childhood and maternal obesity. The concept of metabolic programming is highly topical, and in this context, describes a predisposition of offspring of obese mothers to the development of obesity independent of environmental factors. Research published in this issue of Clinical Science conducted by Litzenburger and colleagues (Clin. Sci. (Lond.) (2020) 134, 921–939) have identified sex-dependent differences in metabolic programming and identify putative signaling pathways involved in the differential phenotype of adipose tissue between males and females. Delineating the distinction between metabolically healthy and unhealthy obesity is a topic of emerging interest, and the precise nature of adipocytes are key to pathogenesis, independent of adipose tissue volume.

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Long-Term Severe In Vitro Hypoxia Exposure Enhances the Vascularization Potential of Human Adipose Tissue-Derived Stromal Vascular Fraction Cell Engineered Tissues

International Journal of Molecular Sciences ◽

10.3390/ijms22157920 ◽

2021 ◽

Vol 22 (15) ◽

pp. 7920

Author(s):

Myroslava Mytsyk ◽

Giulia Cerino ◽

Gregory Reid ◽

Laia Gili Sole ◽

Friedrich S. Eckstein ◽

...

Keyword(s):

Adipose Tissue ◽

Therapeutic Potential ◽

Stromal Vascular Fraction ◽

Human Adipose Tissue ◽

Bioreactor Culture ◽

Proliferating Cells ◽

Angiogenic Potential ◽

Engineered Tissues

The therapeutic potential of mesenchymal stromal/stem cells (MSC) for treating cardiac ischemia strongly depends on their paracrine-mediated effects and their engraftment capacity in a hostile environment such as the infarcted myocardium. Adipose tissue-derived stromal vascular fraction (SVF) cells are a mixed population composed mainly of MSC and vascular cells, well known for their high angiogenic potential. A previous study showed that the angiogenic potential of SVF cells was further increased following their in vitro organization in an engineered tissue (patch) after perfusion-based bioreactor culture. This study aimed to investigate the possible changes in the cellular SVF composition, in vivo angiogenic potential, as well as engraftment capability upon in vitro culture in harsh hypoxia conditions. This mimics the possible delayed vascularization of the patch upon implantation in a low perfused myocardium. To this purpose, human SVF cells were seeded on a collagen sponge, cultured for 5 days in a perfusion-based bioreactor under normoxia or hypoxia (21% and <1% of oxygen tension, respectively) and subcutaneously implanted in nude rats for 3 and 28 days. Compared to ambient condition culture, hypoxic tension did not alter the SVF composition in vitro, showing similar numbers of MSC as well as endothelial and mural cells. Nevertheless, in vitro hypoxic culture significantly increased the release of vascular endothelial growth factor (p < 0.001) and the number of proliferating cells (p < 0.00001). Moreover, compared to ambient oxygen culture, exposure to hypoxia significantly enhanced the vessel length density in the engineered tissues following 28 days of implantation. The number of human cells and human proliferating cells in hypoxia-cultured constructs was also significantly increased after 3 and 28 days in vivo, compared to normoxia. These findings show that a possible in vivo delay in oxygen supply might not impair the vascularization potential of SVF- patches, which qualifies them for evaluation in a myocardial ischemia model.

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DsbA-L deficiency in T cells promotes diet-induced thermogenesis through suppressing IFN-γ production

Nature Communications ◽

10.1038/s41467-020-20665-4 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Haiyan Zhou ◽

Xinyi Peng ◽

Jie Hu ◽

Liwen Wang ◽

Hairong Luo ◽

...

Keyword(s):

T Cells ◽

Adipose Tissue ◽

T Cell ◽

Energy Homeostasis ◽

Metabolic Diseases ◽

Therapeutic Potential ◽

Whole Body ◽

Brown Adipose ◽

Ifn Γ ◽

Diet Induced Thermogenesis

AbstractAdipose tissue-resident T cells have been recognized as a critical regulator of thermogenesis and energy expenditure, yet the underlying mechanisms remain unclear. Here, we show that high-fat diet (HFD) feeding greatly suppresses the expression of disulfide-bond A oxidoreductase-like protein (DsbA-L), a mitochondria-localized chaperone protein, in adipose-resident T cells, which correlates with reduced T cell mitochondrial function. T cell-specific knockout of DsbA-L enhances diet-induced thermogenesis in brown adipose tissue (BAT) and protects mice from HFD-induced obesity, hepatosteatosis, and insulin resistance. Mechanistically, DsbA-L deficiency in T cells reduces IFN-γ production and activates protein kinase A by reducing phosphodiesterase-4D expression, leading to increased BAT thermogenesis. Taken together, our study uncovers a mechanism by which T cells communicate with brown adipocytes to regulate BAT thermogenesis and whole-body energy homeostasis. Our findings highlight a therapeutic potential of targeting T cells for the treatment of over nutrition-induced obesity and its associated metabolic diseases.

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Irisin induces white adipose tissue browning in mice as assessed by magnetic resonance imaging

Experimental Biology and Medicine ◽

10.1177/15353702211006049 ◽

2021 ◽

pp. 153537022110060

Author(s):

Yue Chen ◽

Jie Ding ◽

Yufei Zhao ◽

Shenghong Ju ◽

Hui Mao ◽

...

Keyword(s):

Magnetic Resonance Imaging ◽

Adipose Tissue ◽

Magnetic Resonance ◽

White Adipose Tissue ◽

High Fat Diet ◽

Chow Diet ◽

Resonance Imaging ◽

High Fat ◽

White Adipocytes ◽

Fat Fraction

This study aimed to track and evaluate the effect of low-dose irisin on the browning of white adipose tissue (WAT) in mice using magnetic resonance imaging (MRI) noninvasively in vivo. Mature white adipocytes extracted from mice were cultured, induced and characterized before being treated by irisin. The volume and fat fraction of WAT were quantified using MRI in normal chow diet and high fat mice after injection of irisin. The browning of cultured white adipocytes and WAT in mice were validated by immunohistochemistry and western blotting for uncoupling protein 1 (UCP1) and deiodinase type II (DIO2). The serum indexes were examined with high fat diet after irisin intervention. UCP1 and DIO2 in adipocytes showed increases responding to the irisin treatment. The size of white adipocytes in mice receiving irisin intervention was reduced. MRI measured volumes and fat fraction of WAT were significantly lower after Irisin treatment. Blood glucose and cholesterol levels were reduced in high fat diet mice after irisin treatment. Irisin intervention exerted browning of WAT, resulting reduction of volume and fat fraction of WAT as measured by MRI. Furthermore, it improved the condition of mice with diet-induced obesity and related metabolic disorders.

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Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

Nature Communications ◽

10.1038/s41467-021-22579-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Anastasia Georgiadi ◽

Valeria Lopez-Salazar ◽

Rabih El- Merahbi ◽

Rhoda Anane Karikari ◽

Xiaochuan Ma ◽

...

Keyword(s):

Adipose Tissue ◽

White Adipose Tissue ◽

Dependent Manner ◽

Metabolic Dysfunction ◽

Functional Interaction ◽

White Adipocyte ◽

White Adipocytes ◽

Obesity And Diabetes ◽

Adhesion Gpcr ◽

Circulating Levels

AbstractThe proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes.

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Contribution of PGC-1α to Obesity- and Caloric Restriction-Related Physiological Changes in White Adipose Tissue

International Journal of Molecular Sciences ◽

10.3390/ijms22116025 ◽

2021 ◽

Vol 22 (11) ◽

pp. 6025

Author(s):

Masaki Kobayashi ◽

Yusuke Deguchi ◽

Yuka Nozaki ◽

Yoshikazu Higami

Keyword(s):

Adipose Tissue ◽

Caloric Restriction ◽

White Adipose Tissue ◽

Mitochondrial Gene ◽

Energy Resource ◽

Peroxisome Proliferator ◽

Physiological Changes ◽

Mitochondrial Gene Expression ◽

Peroxisome Proliferator Activated Receptor ◽

White Adipocytes

Peroxisome proliferator-activated receptor γ coactivator-1 α (PGC-1α) regulates mitochondrial DNA replication and mitochondrial gene expression by interacting with several transcription factors. White adipose tissue (WAT) mainly comprises adipocytes that store triglycerides as an energy resource and secrete adipokines. The characteristics of WAT vary in response to systemic and chronic metabolic alterations, including obesity or caloric restriction. Despite a small amount of mitochondria in white adipocytes, accumulated evidence suggests that mitochondria are strongly related to adipocyte-specific functions, such as adipogenesis and lipogenesis, as well as oxidative metabolism for energy supply. Therefore, PGC-1α is expected to play an important role in WAT. In this review, we provide an overview of the involvement of mitochondria and PGC-1α with obesity- and caloric restriction-related physiological changes in adipocytes and WAT.

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Irisin exerts dual effects on browning and adipogenesis of human white adipocytes

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00094.2016 ◽

2016 ◽

Vol 311 (2) ◽

pp. E530-E541 ◽

Cited By ~ 64

Author(s):

Yuan Zhang ◽

Chao Xie ◽

Hai Wang ◽

Robin M. Foss ◽

Morgan Clare ◽

...

Keyword(s):

Adipose Tissue ◽

Uncoupling Protein ◽

Adipogenic Differentiation ◽

Mapk Signaling ◽

Cellular Energy ◽

Subcutaneous White Adipose Tissue ◽

Basal Expression ◽

White Adipocytes ◽

Ucp1 Expression

To better understand the role of irisin in humans, we examined the effects of irisin in human primary adipocytes and fresh human subcutaneous white adipose tissue (scWAT). Human primary adipocytes derived from 28 female donors' fresh scWAT were used to examine the effects of irisin on browning and mitochondrial respiration, and preadipocytes were used to examine the effects of irisin on adipogenesis and osteogenesis. Cultured fragments of scWAT and perirenal brown fat were used for investigating signal transduction pathways that mediate irisin's browning effect by Western blotting to detect phosphorylated forms of p38, ERK, and STAT3 as well as uncoupling protein 1 (UCP1). Individual responses to irisin in scWAT were correlated with basal expression levels of brown/beige genes. Irisin upregulated the expression of browning-associated genes and UCP1 protein in both cultured primary mature adipocytes and fresh adipose tissues. It also significantly increased thermogenesis at 5 nmol/l by elevating cellular energy metabolism (OCR and ECAR). Treating human scWAT with irisin increased UCP1 expression by activating the ERK and p38 MAPK signaling. Blocking either pathway with specific inhibitors abolished irisin-induced UCP1 upregulation. However, our results showed that UCP1 in human perirenal adipose tissue was insensitive to irisin. Basal levels of brown/beige and FNDC5 genes correlated positively with the browning response of scWAT to irisin. In addition, irisin significantly inhibited adipogenic differentiation but promoted osteogenic differentiation. We conclude that irisin promotes “browning” of mature white adipocytes by increasing cellular thermogenesis, whereas it inhibits adipogenesis and promotes osteogenesis during lineage-specific differentiation. Our findings provide a rationale for further exploring the therapeutic use of irisin in obesity and exercise-associated bone formation.

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Vitamin D signalling in adipose tissue

British Journal Of Nutrition ◽

10.1017/s0007114512003285 ◽

2012 ◽

Vol 108 (11) ◽

pp. 1915-1923 ◽

Cited By ~ 161

Author(s):

Cherlyn Ding ◽

Dan Gao ◽

John Wilding ◽

Paul Trayhurn ◽

Chen Bing

Keyword(s):

Vitamin D ◽

Adipose Tissue ◽

Vitamin D Deficiency ◽

Vitamin D Metabolites ◽

Hydroxyvitamin D ◽

The Metabolic Syndrome ◽

Prevalence Of Obesity ◽

Adipose Tissue Development ◽

And Function

Vitamin D deficiency and the rapid increase in the prevalence of obesity are both considered important public health issues. The classical role of vitamin D is in Ca homoeostasis and bone metabolism. Growing evidence suggests that the vitamin D system has a range of physiological functions, with vitamin D deficiency contributing to the pathogenesis of several major diseases, including obesity and the metabolic syndrome. Clinical studies have shown that obese individuals tend to have a low vitamin D status, which may link to the dysregulation of white adipose tissue. Recent studies suggest that adipose tissue may be a direct target of vitamin D. The expression of both the vitamin D receptor and 25-hydroxyvitamin D 1α-hydroxylase (CYP27B1) genes has been shown in murine and human adipocytes. There is evidence that vitamin D affects body fat mass by inhibiting adipogenic transcription factors and lipid accumulation during adipocyte differentiation. Some recent studies demonstrate that vitamin D metabolites also influence adipokine production and the inflammatory response in adipose tissue. Therefore, vitamin D deficiency may compromise the normal metabolic functioning of adipose tissue. Given the importance of the tissue in energy balance, lipid metabolism and inflammation in obesity, understanding the mechanisms of vitamin D action in adipocytes may have a significant impact on the maintenance of metabolic health. In the present review, we focus on the signalling role of vitamin D in adipocytes, particularly the potential mechanisms through which vitamin D may influence adipose tissue development and function.

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