2020
DOI: 10.1002/advs.201903366
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Transferrin Receptor 1 Regulates Thermogenic Capacity and Cell Fate in Brown/Beige Adipocytes

Abstract: Iron homeostasis is essential for maintaining cellular function in a wide range of cell types. However, whether iron affects the thermogenic properties of adipocytes is currently unknown. Using integrative analyses of multi‐omics data, transferrin receptor 1 (Tfr1) is identified as a candidate for regulating thermogenesis in beige adipocytes. Furthermore, it is shown that mice lacking Tfr1 specifically in adipocytes have impaired thermogenesis, increased insulin resistance, and low‐grade inflammation accompani… Show more

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Cited by 42 publications
(59 citation statements)
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“…Under physiological conditions, ferric iron in the form of transferrin-bound iron (TBI) recognized by membrane Tfr1 is absorbed in peripheral tissues, such as liver, adipose tissue, skeletal muscle, and bone marrow (23, 41, 42) . Multiple studies have shown that Tfr1 -deficiency results in functional disorder and even death.…”
Section: Discussionmentioning
confidence: 99%
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“…Under physiological conditions, ferric iron in the form of transferrin-bound iron (TBI) recognized by membrane Tfr1 is absorbed in peripheral tissues, such as liver, adipose tissue, skeletal muscle, and bone marrow (23, 41, 42) . Multiple studies have shown that Tfr1 -deficiency results in functional disorder and even death.…”
Section: Discussionmentioning
confidence: 99%
“…Mice with Tfr1 conditional knockout in hematopoietic stem cells died within one week after birth (43) . Our previous study demonstrated that Tfr1 regulates adipocyte thermogenesis and cell fate determination (44) . Adipocytes with Tfr1 ablation exhibit reduced thermogenic capacity and beigeing potential (44) .…”
Section: Discussionmentioning
confidence: 99%
“…To study the effects of adipocyte-specific iron homeostasis on metabolism, models in which iron import and export proteins have been ablated, provide important insights. Adipocyte-targeted knock down of iron handling proteins [ 31 , 40 ] in vitro and in vivo are generally associated with dysfunctional elevation in inflammation and reductions in insulin signaling. For example, human adipocytes lacking lactoferrin showed increased expression of inflammatory genes [ 31 ].…”
mentioning
confidence: 99%
“…On a high-fat diet, these mice have increased markers of AT inflammation, dysregulated lipid metabolism, mount a defective thermogenic response, and develop insulin resistance. Interestingly, these effects were thought to be regulated by HIF1α activation in beige adipocytes [ 40 ]. This is entirely in line with the observations noted above in the KK/HIJ and obese anemic mice [ 32 , 37 ].…”
mentioning
confidence: 99%
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