A direct tissue-grafting approach to increasing endogenous brown fat

Blumenfeld, Nicole R.; Kang, Hwan June; Fenzl, Anna; Song, Ziwei; Chung, Janice; Singh, Ranjodh; Johnson, Roshawn; Karakeçili, Ayşe; Feranil, Jun B.; Rossen, Ninna S.; Zhang, Vivian; Jaggi, Sahir; McCarty, Bret; Bessler, Steven; Schwartz, Gary J.; Grant, Robert T.; Körner, Judith; Kiefer, Florian W.; Gillette, Brian M.; Sia, Samuel K.

doi:10.1038/s41598-018-25866-y

Cited by 37 publications

(31 citation statements)

References 62 publications

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“…Moreover, mice with diet-induced obesity, 4 months after injection with converted beige adipocytes, had lower body weight than those injected with control WAT. Importantly, the ex vivo conversion of white adipocytes into UCP1-expressing beige cells was also achieved in human tissues [ 116 ].…”

Section: Non-pharmacological Interventions Aiming At White Adiposementioning

confidence: 99%

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Kuryłowicz

Puzianowska-Kuźnicka

2020

IJMS

148

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The ongoing obesity pandemic generates a constant need to develop new therapeutic strategies to restore the energy balance. Therefore, the concept of activating brown adipose tissue (BAT) in order to increase energy expenditure has been revived. In mammals, two developmentally distinct types of brown adipocytes exist; the classical or constitutive BAT that arises during embryogenesis, and the beige adipose tissue that is recruited postnatally within white adipose tissue (WAT) in the process called browning. Research of recent years has significantly increased our understanding of the mechanisms involved in BAT activation and WAT browning. They also allowed for the identification of critical molecules and critical steps of both processes and, therefore, many new therapeutic targets. Several non-pharmacological approaches, as well as chemical compounds aiming at the induction of WAT browning and BAT activation, have been tested in vitro as well as in animal models of genetically determined and/or diet-induced obesity. The therapeutic potential of some of these strategies has also been tested in humans. In this review, we summarize present concepts regarding potential therapeutic targets in the process of BAT activation and WAT browning and available strategies aiming at them.

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Section: Non-pharmacological Interventions Aiming At White Adiposementioning

confidence: 99%

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Kuryłowicz

Puzianowska-Kuźnicka

2020

IJMS

148

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“…X-ray data collection and refinement statistics. References (61)(62)(63)(64)(65)(66)(67)(68)(69)(70) View/request a protocol for this paper from Bio-protocol.…”

Section: Supplementary Materialsmentioning

confidence: 99%

Retinol-binding protein 2 (RBP2) binds monoacylglycerols and modulates gut endocrine signaling and body weight

et al. 2020

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Expressed in the small intestine, retinol-binding protein 2 (RBP2) facilitates dietary retinoid absorption. Rbp2-deficient (Rbp2−/−) mice fed a chow diet exhibit by 6-7 months-of-age higher body weights, impaired glucose metabolism, and greater hepatic triglyceride levels compared to controls. These phenotypes are also observed when young Rbp2−/− mice are fed a high fat diet. Retinoids do not account for the phenotypes. Rather, RBP2 is a previously unidentified monoacylglycerol (MAG)-binding protein, interacting with the endocannabinoid 2-arachidonoylglycerol (2-AG) and other MAGs with affinities comparable to retinol. X-ray crystallographic studies show that MAGs bind in the retinol binding pocket. When challenged with an oil gavage, Rbp2−/− mice show elevated mucosal levels of 2-MAGs. This is accompanied by significantly elevated blood levels of the gut hormone GIP (glucose-dependent insulinotropic polypeptide). Thus, RBP2, in addition to facilitating dietary retinoid absorption, modulates MAG metabolism and likely signaling, playing a heretofore unknown role in systemic energy balance.

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“…BAT plays a potential endocrine role against hypertensive cardiac remodeling in DOCA-salt induced hypertension [5]. Tissue-grafting of converted BAT has been proposed as a direct approach to increase endogenous brown fat in vivo [26]. In order to directly con rm the role of BAT in AngII-induced hypertension in mice, we rstly detected and compared the changes of iBAT in hypertensive mice to WT control mice, the results showed extensive brown-to-white adipose transformation in the iBAT extracted from the Ang II-infused mice but no change in the control mice.…”

Section: Discussionmentioning

confidence: 99%

Mitochondrial Activity Regulates Skin-derived Mesenchymal Stem Cell Differentiation Into Brown Adipocyte Contributing to Hypertension

Chen

Sun

et al. 2020

Preprint

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Background: Brown adipocytes (BAs) are the major component of brown adipose tissue (BAT) that is closely related to systemic hypertension. BAs are derived from multiple progenitors including PDGFRα+ adipose-derived stem cells (ASCs). Skin-derived Mesenchymal Stem Cells (S-MSCs) have the capacity to differentiate into adipocytes. However, the differentiation of S-MSCs into BAs remains unexplored. We aim to study the ability and regulation mechanism of S-MSCs differentiation into BAs, and the direct role of BAT in blood pressure regulation. Methods: Protein expression was measured by Flow Cytometry or Western blotting, and gene mRNA levels were detected by real-time quantitative PCR (RT-PCR). For the BA differentiation of S-MSCs, S-MSCs were stimulated with a brown adipogenic cocktail containing insulin, IBMX, dexamethasone, triiodothyronine (T3), and rosiglitazone for the indicated periods. The oxygen consumption rate (OCR) was measured with an XF24 Extracellular Flux Analyzer. Mitochondrial mass was checked by flow cytometry and fluorescence staining. Hypertensive mouse model was induced in WT mice by infusion with angiotensin II (Ang II) and measured SBP using tail-cuff. The interscapular brown adipose tissue (iBAT)-deficiency mice were gotten by surgically removing the iBAT depot and allowed to recover for 6 days. Aorta, iBAT or heart tissue sections were examined by hematoxylin and eosin (HE) staining. Results: We found that S-MSCs isolated from the mouse dermis expressed the stem cell markers CD90/105 and PDGFRα, and readily differentiated into BAs. Mitochondrial biogenesis and oxygen consumption were markedly increased during BA differentiation of S-MSCs in vitro. Another, Ang II-induced hypertensive mice carried the change of iBAT to white adipose tissue (WAT), the enhanced Ang II-induced blood pressure and vascular remodeling were observed in BAT-deficient mice generated by surgically removing iBAT comparing with C57BL/6 (wild type-WT) mice. Conclusions: S-MSCs represent a useful in vitro model for differentiation of BAs regulated by mitochondrial activity, and are progenitors of BAs. This study indicates that PDGFRα+ S-MSCs could differentiate into BAs, and BAT plays a direct role in Ang II-induced hypertension and target organ remodeling.

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A direct tissue-grafting approach to increasing endogenous brown fat

Cited by 37 publications

References 62 publications

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Induction of Adipose Tissue Browning as a Strategy to Combat Obesity

Retinol-binding protein 2 (RBP2) binds monoacylglycerols and modulates gut endocrine signaling and body weight

Mitochondrial Activity Regulates Skin-derived Mesenchymal Stem Cell Differentiation Into Brown Adipocyte Contributing to Hypertension

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