A stringent validation of mouse adipose tissue identity markers

The nature of brown adipose tissue in humans is presently debated: whether it is classical brown or of brite/beige nature. The dissimilar developmental origins and proposed distinct functions of the brown and brite/beige tissues make it essential to ascertain the identity of human depots with the perspective of recruiting and activating them for the treatment of obesity and type 2 diabetes. For identification of the tissues, a number of marker genes have been proposed, but the validity of the markers has not been well documented. We used established brown (interscapular), brite (inguinal), and white (epididymal) mouse adipose tissues and corresponding primary cell cultures as validators and examined the informative value of a series of suggested markers earlier used in the discussion considering the nature of human brown adipose tissue. Most of these markers unexpectedly turned out to be noninformative concerning tissue classification ( Car4, Cited1, Ebf3, Eva1, Fbxo31, Fgf21, Lhx8, Hoxc8, and Hoxc9). Only Zic1 (brown), Cd137, Epsti1, Tbx1, Tmem26 (brite), and Tcf21 (white) proved to be informative in these three tissues. However, the expression of the brite markers was not maintained in cell culture. In a more extensive set of adipose depots, these validated markers provide new information about depot identity. Principal component analysis supported our single-gene conclusions. Furthermore, Zic1, Hoxc8, Hoxc9, and Tcf21 displayed anteroposterior expression patterns, indicating a relationship between anatomic localization and adipose tissue identity (and possibly function). Together, the observed expression patterns of these validated marker genes necessitates reconsideration of adipose depot identity in mice and humans.

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Brown adipose tissue: development, metabolism and beyond

Biochemical Journal ◽

10.1042/bj20130457 ◽

2013 ◽

Vol 453 (2) ◽

pp. 167-178 ◽

Cited By ~ 94

Author(s):

Tim J. Schulz ◽

Yu-Hua Tseng

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Fat ◽

Alcoholic Fatty Liver ◽

Fat Depots ◽

Brown Adipose ◽

Large Lipid Droplet ◽

Adipose Tissue Development ◽

Treatment Of Obesity

Obesity represents a major risk factor for the development of several of our most common medical conditions, including Type 2 diabetes, dyslipidaemia, non-alcoholic fatty liver, cardiovascular disease and even some cancers. Although increased fat mass is the main feature of obesity, not all fat depots are created equal. Adipocytes found in white adipose tissue contain a single large lipid droplet and play well-known roles in energy storage. By contrast, brown adipose tissue is specialized for thermogenic energy expenditure. Owing to its significant capacity to dissipate energy and regulate triacylglycerol (triglyceride) and glucose metabolism, and its demonstrated presence in adult humans, brown fat could be a potential target for the treatment of obesity and metabolic syndrome. Undoubtedly, fundamental knowledge about the formation of brown fat and regulation of its activity is imperatively needed to make such therapeutics possible. In the present review, we integrate the recent advancements on the regulation of brown fat formation and activity by developmental and hormonal signals in relation to its metabolic function.

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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Effects of stem cells from inducible brown adipose tissue on diet-induced obesity in mice

Scientific Reports ◽

10.1038/s41598-021-93224-6 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Enrique Calvo ◽

Noelia Keiran ◽

Catalina Núñez-Roa ◽

Elsa Maymó-Masip ◽

Miriam Ejarque ◽

...

Keyword(s):

Stem Cells ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Therapeutic Option ◽

Metabolic Activation ◽

Diet Induced Obesity ◽

Brown Adipose ◽

Obesity In Mice ◽

Treatment Of Obesity ◽

Visceral Adipose

AbstractAdipose-derived mesenchymal stem cells (ASCs) are a promising option for the treatment of obesity and its metabolic co-morbidities. Despite the recent identification of brown adipose tissue (BAT) as a potential target in the management of obesity, the use of ASCs isolated from BAT as a therapy for patients with obesity has not yet been explored. Metabolic activation of BAT has been shown to have not only thermogenic effects, but it also triggers the secretion of factors that confer protection against obesity. Herein, we isolated and characterized ASCs from the visceral adipose tissue surrounding a pheochromocytoma (IB-hASCs), a model of inducible BAT in humans. We then compared the anti-obesity properties of IB-hASCs and human ASCs isolated from visceral white adipose tissue (W-hASCs) in a murine model of diet-induced obesity. We found that both ASC therapies mitigated the metabolic abnormalities of obesity to a similar extent, including reducing weight gain and improving glucose tolerance. However, infusion of IB-hASCs was superior to W-hASCs in suppressing lipogenic and inflammatory markers, as well as preserving insulin secretion. Our findings provide evidence for the metabolic benefits of visceral ASC infusion and support further studies on IB-hASCs as a therapeutic option for obesity-related comorbidities.

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Dopaminergic Input from the Posterior Hypothalamus to the Raphe Pallidus Area Inhibits Brown Adipose Tissue Thermogenesis

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.00149.2021 ◽

2021 ◽

Author(s):

Ellen Paula Santos da Conceição Furber ◽

Clarissa M.D. Mota ◽

Edward Veytsman ◽

Shaun F. Morrison ◽

Christopher J. Madden

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Posterior Hypothalamus ◽

Brown Adipose ◽

Premotor Neurons ◽

Brown Adipose Tissue Thermogenesis ◽

Pre Treatment ◽

Type 3 ◽

Raphe Pallidus

Systemic administration of dopamine (DA) receptor agonists leads to falls in body temperature. However, the central thermoregulatory pathways modulated by DA have not been fully elucidated. Here we identified a source and site of action contributing to DA's hypothermic action by inhibition of brown adipose tissue (BAT) thermogenesis. Nanoinjection of the type 2 and type 3 DA receptor (D2R/D3R) agonist, 7-OH-DPAT, in the rostral raphe pallidus area (rRPa) inhibits the sympathetic activation of BAT evoked by cold exposure or by direct activation of NMDA receptors in the rRPa. Blockade of D2R/D3R in the rRPa with nanoinjection of SB-277011A increases BAT thermogenesis, consistent with a tonic release of DA in the rRPa contributing to inhibition of BAT thermogenesis. Accordingly, D2R are expressed in cold-activated and serotonergic neurons in the rRPa and anatomical tracing studies revealed that neurons in the posterior hypothalamus (PH) are a source of dopaminergic input to the rRPa. Disinhibitory activation of PH neurons with nanoinjection of gabazine inhibits BAT thermogenesis, which is reduced by pre-treatment of the rRPa with SB-277011A. In conclusion, the rRPa, the site of sympathetic premotor neurons for BAT, receives a tonically-active, dopaminergic input from the PH that suppresses BAT thermogenesis.

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Anti-Obesity Effects of Grateloupia elliptica, a Red Seaweed, in Mice with High-Fat Diet-Induced Obesity via Suppression of Adipogenic Factors in White Adipose Tissue and Increased Thermogenic Factors in Brown Adipose Tissue

Nutrients ◽

10.3390/nu12020308 ◽

2020 ◽

Vol 12 (2) ◽

pp. 308 ◽

Cited By ~ 4

Author(s):

Hyo-Geun Lee ◽

Yu An Lu ◽

Xining Li ◽

Ji-Min Hyun ◽

Hyun-Soo Kim ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

White Adipose Tissue ◽

High Fat Diet ◽

Red Seaweed ◽

High Fat ◽

Adipose Tissues ◽

Ppar Γ ◽

Brown Adipose ◽

Treatment Of Obesity

Obesity is a serious metabolic syndrome characterized by high levels of cholesterol, lipids in the blood, and intracellular fat accumulation in adipose tissues. It is known that the suppression of adipogenic protein expression is an effective approach for the treatment of obesity, and regulates fatty acid storage and transportation in adipose tissues. The 60% ethanol extract of Grateloupia elliptica (GEE), a red seaweed from Jeju Island in Korea, was shown to exert anti-adipogenic activity in 3T3-L1 cells and in mice with high-fat diet (HFD)-induced obesity. GEE inhibited intracellular lipid accumulation in 3T3-L1 cells, and significantly reduced expression of adipogenic proteins. In vivo experiments indicated a significant reduction in body weight, as well as white adipose tissue (WAT) weight, including fatty liver, serum triglycerides, total cholesterol, and leptin contents. The expression of the adipogenic proteins, SREBP-1 and PPAR-γ, was significantly decreased by GEE, and the expression of the metabolic regulator protein was increased in WAT. The potential of GEE was shown in WAT, with the downregulation of PPAR-γ and C/EBP-α mRNA; in contrast, in brown adipose tissue (BAT), the thermogenic proteins were increased. Collectively, these research findings suggest the potential of GEE as an effective candidate for the treatment of obesity-related issues via functional foods or pharmaceutical agents.

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Inhibition of Type 1 Iodothyronine Deiodinase by Bisphenol A

Hormone and Metabolic Research ◽

10.1055/a-0919-3879 ◽

2019 ◽

Vol 51 (10) ◽

pp. 671-677 ◽

Cited By ~ 7

Author(s):

Maurício Martins da Silva ◽

Carlos Frederico Lima Gonçalves ◽

Leandro Miranda-Alves ◽

Rodrigo Soares Fortunato ◽

Denise P. Carvalho ◽

...

Keyword(s):

Adipose Tissue ◽

Thyroid Hormone ◽

Bisphenol A ◽

Brown Adipose Tissue ◽

Tissue Type ◽

Deiodinase Activity ◽

Brown Adipose

AbstractPlastics are ubiquitously present in our daily life and some components of plastics are endocrine-disrupting chemicals, such as bisphenol A and phthalates. Herein, we aimed to evaluate the effect of plastic endocrine disruptors on type 1 and type 2 deiodinase activities, enzymes responsible for the conversion of the pro-hormone T4 into the biologically active thyroid hormone T3, both in vitro and in vivo. Initially, we incubated rat liver type 1 deiodinase and brown adipose tissue type 2 deiodinase samples with 0.5 mM of the plasticizers, and the deiodinase activity was measured. Among them, only BPA was capable to inhibit both type 1 and type 2 deiodinases. Then, adult male Wistar rats were treated orally with bisphenol A (40 mg/kg b.w.) for 15 days and hepatic type 1 deiodinase and brown adipose tissue type 2 deiodinase activities and serum thyroid hormone concentrations were measured. In vivo bisphenol A treatment significantly reduced hepatic type 1 deiodinase activity but did not affect brown adipose tissue type 2 deiodinase activity. Serum T4 levels were higher in bisphenol A group, while T3 remained unchanged. T3/T4 ratio was decreased in rats treated with bisphenol A, reinforcing the idea that peripheral metabolism of thyroid hormone was affected by bisphenol A exposure. Therefore, our results suggest that bisphenol A can affect the metabolism of thyroid hormone thus disrupting thyroid signaling.

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Relationship of brown adipose tissue with growth and obesity differences in genetically selected mouse lines

Canadian Journal of Genetics and Cytology ◽

10.1139/g84-053 ◽

1984 ◽

Vol 26 (3) ◽

pp. 339-347 ◽

Cited By ~ 1

Author(s):

A. M. Saxton ◽

E. J. Eisen ◽

J. M. Leatherwood

Keyword(s):

Body Weight ◽

Adipose Tissue ◽

Brown Adipose Tissue ◽

Single Gene ◽

Tissue Growth ◽

Growth Patterns ◽

High Fat ◽

Polygenic Control ◽

Brown Adipose ◽

Diet Induced Thermogenesis

A recent hypothesis considers brown adipose tissue (BAT) to be an important source of diet-induced thermogenesis (DIT). In turn, DIT and thermogenesis in general are believed to be key factors in the control of obesity of laboratory rodents. This hypothesis was developed from the study of single gene mutant obese rodents. The present research tested this hypothesis in mice with polygenic control of growth and obesity, which is more characteristic of the type of genetic variation expected in human and other mammalian populations. Control and high fat diets were used to test responses of five genetically selected lines of mice showing different patterns of growth and obesity. All lines deposited more fat on the high fat diet, but the most obese line showed the largest increase in BAT and the lipid-free dry (LFD) component of BAT. Use of LFD per unit body weight gave results which supported the hypothesis being tested, but it was argued that this measure is misleading. When brown and white adipose tissue growth relative to body weight were examined, 2 of the 10 line – diet groups showed alterations in BAT growth patterns. However, it was concluded that BAT, if involved at all, was not a major factor in growth and obesity differences.Key words: obesity, polygenes, adipose tissue, quantitative inheritance, mouse.

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