The beneficial effects of brown adipose tissue transplantation

White, Joseph; Dewal, Revati S.; Stanford, Kristin I.

doi:10.1016/j.mam.2019.06.004

Cited by 95 publications

(78 citation statements)

References 125 publications

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“…The recent confirmation that adult humans have brown adipose tissue has transformed our understanding of how adipose tissue regulates metabolism and energy balance [34], [35]. Many researchers emphasize that fat burning in adipose tissue can improve obesity induced metabolic impairment [36], [37]. In fact, inflammation and the immune system also play essential role in energy expenditure and metabolic syndrome [38], [39], [40].…”

Section: Discussionmentioning

confidence: 99%

cAMP-MicroRNA-203-IFNγ network regulates subcutaneous white fat browning and glucose tolerance

Guo

Zhang

Zeng

et al. 2019

Molecular Metabolism

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ObjectiveBrown and beige adipocytes in humans and rodents are specialized to burn lipids for heat generation as a natural defense against cold and obesity, which is advantageous to metabolic homeostasis. MicroRNAs as another regulatory layer to regulate metabolic homeostasis attracted a lot of attentions. Our previous work revealed microRNA (miR)-203 as a brown adipocyte-enriched microRNA involved in brown adipocytes development. However, the potential role of miR-203 in adipose tissue metabolic homeostasis has not been determined in vivo. In this study, we investigate the potential role of miR-203 in subcutaneous white adipose tissue (sub-WAT) browning and metabolic homeostasis.MethodsWe investigated the relationship between miR-203 and energy homeostasis in adipose tissue from cold exposed, high fat diet (HFD) fed, ob/ob and db/db mice. The functions of miR-203 on sub-WAT browning were validated through miR-203 knockdown or overexpression. The miR-203 targeted signal pathway was screened by RNAseq analysis. Luciferase report assay, western blot, and qPCR were performed to establish the miR-203 related upstream and downstream signal pathway in vivo and in vitro. The functions of miR-203 on obesity and metabolic homeostasis were validated through GTT/ITT and western blot on high fat diet-induced obesity in C57 mice. ELISA was used to determine the concentration of IFN-γ. Flow cytometry analysis was performed to determine the infiltration of macrophages in adipose tissue.ResultsMiR-203 expression positively correlates with energy expenditure, and overexpression of miR-203 could enhance sub-WAT browning in normal diet (ND) condition. Mechanistically, the expression of miR-203 is activated by cAMP-dependent C/EBPβ up-regulation. Subsequently, miR-203 inhibits IFN-γ signal pathway activation by directly targeting Lyn, which is an activator of Jak1-Stat1. Moreover, the forced expression of miR-203 could improve insulin sensitivity and resist high fat diet-induced obesity by inhibiting IFN-γ.ConclusionsMicroRNA-203 (miR-203) promotes white adipose tissue browning in cold exposed mice and improves glucose tolerance in HFD fed mice by repressing IFN-γ. Since miR-203 is activated by cAMP-dependent C/EBPβ up-regulation and directly represses IFN-γ signal pathway, we declare that miR-203 acts as a messenger between cAMP signal pathway and IFN-γ signal pathway.

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Section: Discussionmentioning

confidence: 99%

cAMP-MicroRNA-203-IFNγ network regulates subcutaneous white fat browning and glucose tolerance

Guo

Zhang

Zeng

et al. 2019

Molecular Metabolism

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“…This alternative role is particularly interesting because increasing energy expenditure by promoting browning of WAT has recently emerged as a new putative therapy to alleviate the effects of obesity and prevent insulin resistance and T2D [ 11 , 12 , 111 ]. Indeed, the engraftment of BAT and beige/brown adipocytes, isolated from human adipocyte precursors and transplanted into mouse recipients, results in substantial weight loss, improvements in glucose tolerance, and insulin sensitivity, representing a clinically translatable model [ 112 , 113 ]. Therefore, it is challenging to identify the responsible cellular pathways and intermediates involved in browning independent of the cell cycle regulation.…”

Section: Discussionmentioning

confidence: 99%

Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes

et al. 2020

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Besides its role as a cell cycle and proliferation regulator, the INK4a/ARF (CDKN2A) locus and its associated pathways are thought to play additional functions in the control of energy homeostasis. Genome-wide association studies in humans and rodents have revealed that single nucleotide polymorphisms in this locus are risk factors for obesity and related metabolic diseases including cardiovascular complications and type-2 diabetes (T2D). Recent studies showed that both p16INK4a-CDK4-E2F1/pRB and p19ARF-P53 (p14ARF in humans) related pathways regulate adipose tissue (AT) physiology and adipocyte functions such as lipid storage, inflammation, oxidative activity, and cellular plasticity (browning). Targeting these metabolic pathways in AT emerged as a new putative therapy to alleviate the effects of obesity and prevent T2D. This review aims to provide an overview of the literature linking the INK4a/ARF locus with AT functions, focusing on its mechanisms of action in the regulation of energy homeostasis.

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“…It has been confirmed that BAT transplantation can heighten the level of circulating adiponectin, increase expression of β-AR and fatty acid oxidation-related genes in WAT [ 61 ]. BAT transplantation models successfully demonstrated the improvements in glucose metabolism and insulin sensitivity, as well as reductions in body mass and decreased adiposity in transplant recipients [ 62 ]. BAT transplantation enhanced the uptake of glucose by endogenous BAT, WAT and myocardium, surprisingly, not by skeletal muscles [ 62 ].…”

Section: Bat Transplantationmentioning

confidence: 99%

“…BAT transplantation models successfully demonstrated the improvements in glucose metabolism and insulin sensitivity, as well as reductions in body mass and decreased adiposity in transplant recipients [ 62 ]. BAT transplantation enhanced the uptake of glucose by endogenous BAT, WAT and myocardium, surprisingly, not by skeletal muscles [ 62 ]. Also, it has been shown that transplantation of embryonic BAT can correct type 1 diabetes mellitus (T1DM) in streptozotocin-treated mice and reverse symptoms of clinical diabetes such as polyuria, polydipsia and polyphagia [ 63 ].…”

Section: Bat Transplantationmentioning

confidence: 99%

Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

et al. 2021

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The beneficial effects of brown adipose tissue transplantation

Cited by 95 publications

References 125 publications

cAMP-MicroRNA-203-IFNγ network regulates subcutaneous white fat browning and glucose tolerance

cAMP-MicroRNA-203-IFNγ network regulates subcutaneous white fat browning and glucose tolerance

Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes

Brown and beige adipose tissue: a novel therapeutic strategy for obesity and type 2 diabetes mellitus

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