Beige Fat Maintenance; Toward a Sustained Metabolic Health

Rabiee, Atefeh

doi:10.3389/fendo.2020.00634

Cited by 40 publications

(24 citation statements)

References 169 publications

(210 reference statements)

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“…The brown/beige and white adipocytes derive from common progenitors, but only the brown/beige ones dissipate stored energy through thermogenesis ( Rabiee, 2020 ). Increased mitochondrial uncoupling or mass could support the link between WAT “browning” and thermogenesis.…”

Section: Resultsmentioning

confidence: 99%

HIF3A Inhibition Triggers Browning of White Adipocytes via Metabolic Rewiring

Cuomo

Dell’Aversana

Chioccarelli

et al. 2022

Front. Cell Dev. Biol.

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Maintenance of energy balance between intake and expenditure is a prerequisite of human health, disrupted in severe metabolic diseases, such as obesity and type 2 diabetes (T2D), mainly due to accumulation of white adipose tissue (WAT). WAT undergoes a morphological and energetic remodelling toward brown adipose tissue (BAT) and the BAT activation has anti-obesity potential. The mechanisms or the regulatory factors able to activate BAT thermogenesis have been only partially deciphered. Identifying novel regulators of BAT induction is a question of great importance for fighting obesity and T2D. Here, we evaluated the role of Hif3α in murine pre-adipocyte 3T3-L1 cell line, a versatile and well characterized biological model of adipogenesis, by gain- and loss-of function approaches and in thermogenesis-induced model in vivo. HIF3A is regulated by inflammation, it modulates lypolysis in adipose tissue of obese adults, but its role in energy metabolism has not previously been investigated. We characterized gene and protein expression patterns of adipogenesis and metabolic activity in vitro and mechanistically in vivo. Overexpression of Hif3α in differentiating adipocytes increases white fat cells, whereas silencing of Hif3α promotes “browning” of white cells, activating thermogenesis through upregulation of Ucp1, Elovl3, Prdm16, Dio2 and Ppargc1a genes. Investigating cell metabolism, Seahorse Real-Time Cell Metabolism Analysis showed that silencing of Hif3α resulted in a significant increase of mitochondrial uncoupling with a concomitant increase in acetyl-CoA metabolism and Sirt1 and Sirt3 expression. The causal Hif3α/Ucp1 inverse relation has been validated in Cannabinoid receptor 1 (CB1) knockout, a thermogenesis-induced model in vivo. Our data indicate that Hif3α inhibition triggers “browning” of white adipocytes activating the beneficial thermogenesis rewiring energy metabolism in vitro and in vivo. HIF3A is a novel player that controls the energy metabolism with potential applications in developing therapy to fight metabolic disorders, as obesity, T2D and ultimately cancer.

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Section: Resultsmentioning

confidence: 99%

HIF3A Inhibition Triggers Browning of White Adipocytes via Metabolic Rewiring

Cuomo

Dell’Aversana

Chioccarelli

et al. 2022

Front. Cell Dev. Biol.

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“…The browning of the WAT is accompanied by an increase in the number of mitochondria caused by de novo biogenesis of mitochondria as well as mitochondrial fission (fission separates one into two) [ 370 ]. Contrarily, a reduced number of mitochondria resulted from mitochondrial fusion (fusion joins two mitochondria together), and mitochondrial disappearance (mitophagy) is reported during beige to white fat transition [ 371 , 372 ]. Mitochondrial dysfunction is present in many organs including WAT and BAT.…”

Section: Brown and Beige Adipose Tissue In Obesity Aging And Metabolic Diseasementioning

confidence: 99%

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

Brandão

Poojari

Rabiee

2021

IJMS

Self Cite

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The concerning worldwide increase of obesity and chronic metabolic diseases, such as T2D, dyslipidemia, and cardiovascular disease, motivates further investigations into preventive and alternative therapeutic approaches. Over the past decade, there has been growing evidence that the formation and activation of thermogenic adipocytes (brown and beige) may serve as therapy to treat obesity and its associated diseases owing to its capacity to increase energy expenditure and to modulate circulating lipids and glucose levels. Thus, understanding the molecular mechanism of brown and beige adipocytes formation and activation will facilitate the development of strategies to combat metabolic disorders. Here, we provide a comprehensive overview of pathways and players involved in the development of brown and beige fat, as well as the role of thermogenic adipocytes in energy homeostasis and metabolism. Furthermore, we discuss the alterations in brown and beige adipose tissue function during obesity and explore the therapeutic potential of thermogenic activation to treat metabolic syndrome.

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“…Их подтипы определяются не только локализацией, но и характером активирующих факторов. Бежевые адипоциты формируются при задействовании 3 основных процессов: 1) путем пролиферации и de novo дифференциации из различных пулов предшественников; 2) путем трансдифференциации зрелых белых адипоцитов; 3) путем активации «дремлющих» бежевых клеток [40]. Предшественники бежевых адипоцитов экспрессируют гены SMA (smooth muscle actin), Myh11(myosin heavy chain 11), Pdgfra и Pdgfrb.…”

Section: развитие адипогенезunclassified

The results of immunohistochemical study of antibodies to CYP11B2 in primary hyperaldosteronism

et al. 2021

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Background: Aldosterone-producing adrenocortical adenoma (APA) is responsible for the majority of cases clinically diagnosed as primary aldosteronism. Aldosterone synthase (CYP11B2) is one of the enzymes that play essential roles in aldosterone synthesis and is involved in the pathogenesis of primary aldosteronism. Recent studies have demonstrated that various factors influence the expression and function of CYP11B2 in APA. In particular, somatic mutations, such as gain-of-function and loss-of-function mutations have been identified in several genes, each of which encodes a pivotal protein that affects the calcium signaling pathway, the expression of CYP11B2, and aldosterone production. On the other hand, CYP11B2 also catalyzes the conversion of cortisol to 18-hydroxycortisol and subsequently converts 18-hydroxycortisol to 18-oxocortisol. The article also discusses the clinical significance of 18-oxocortisol, an important biomarker for the diagnosis of primary aldosteronism. Somatic mutations in aldosterone-driver genes are strongly associated with CYP11B2 expression and have been only detected in the CYP11B2-positive tumor area, that indicating heterogeneous expression of CYP11B2 in tumor.Aim: to assess the functional heterogeneity of adrenal tumors in primary aldosteronismMaterials and methods: Retrospective evaluation adrenal tumors from patients with primary aldosteronism (n=20). According to CT unilateral macrohyperplasia was detected in 19 patients (95% of total), all of them were confirmed to have unilateral hyperproduction of aldosterone according to AVS. Selected tumors werestained with anty-CYP11B2 antibody. We evaluated the CYP11B2 expression in the adenoma and in the adjacent adrenal cortex.Results: Immunohistochemistry studies of the resected adrenals from 20 patients with PA operated due to unilateral production of aldosterone using CYP11B2 staining showed that 10 of those with an adenoma on CT scanning showed CYP11B2 staining in the adenoma. Furthermore, 5 cases of an unilateral adenoma, showed CYP11B2 staining in the adjacent adrenal cortex and an absence of staining for CYP11B2 in the adenoma. 5 cases showed CYP11B2 expression is heterogeneously immunolocalized throughout the tumor area.Conclusion: Thus, the functional heterogeneity of adrenal tumors in primary aldosteronism has been proven. It is necessary to compare the data of immunohistochemical studies on the expression of CYP11B2 with the indicators of the level of 18-hydroxycortisol, 18-oxocortisol.

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Beige Fat Maintenance; Toward a Sustained Metabolic Health

Cited by 40 publications

References 169 publications

HIF3A Inhibition Triggers Browning of White Adipocytes via Metabolic Rewiring

HIF3A Inhibition Triggers Browning of White Adipocytes via Metabolic Rewiring

Thermogenic Fat: Development, Physiological Function, and Therapeutic Potential

The results of immunohistochemical study of antibodies to CYP11B2 in primary hyperaldosteronism

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