2021
DOI: 10.1016/j.molmet.2021.101305
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Defective insulin-stimulated GLUT4 translocation in brown adipocytes induces systemic glucose homeostasis dysregulation independent of thermogenesis in female mice

Abstract: Objective Recent studies indicate that brown adipose tissue, in addition to its role in thermogenesis, has a role in the regulation of whole-body metabolism. Here we characterize the metabolic effects of deleting Rab10, a protein key for insulin stimulation of glucose uptake into white adipocytes, solely from brown adipocytes. Methods We used a murine brown adipocyte cell line and stromal vascular fraction-derived in vitro differentiated brown… Show more

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Cited by 12 publications
(5 citation statements)
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“… 70 72 For example, defective GLUT4 translocation or inhibition of GLUT4 in adipocytes induces systemic glucose homeostasis dysregulation and leads to a risk of developing T2DM. 73 , 74 Importantly, thermogenic fat cells can take in more glucose via the GLUT1 than that white fat cells solely rely on GLUT4. 17 , 75 So, given the significant role of thermogenic adipocytes performed in regulating glucose, the impaired capability of thermogenic fat tissue may give rise to metabolic disorders in vivo.…”
Section: The Developmental Origin and Anatomical Location Of Thermoge...mentioning
confidence: 99%
“… 70 72 For example, defective GLUT4 translocation or inhibition of GLUT4 in adipocytes induces systemic glucose homeostasis dysregulation and leads to a risk of developing T2DM. 73 , 74 Importantly, thermogenic fat cells can take in more glucose via the GLUT1 than that white fat cells solely rely on GLUT4. 17 , 75 So, given the significant role of thermogenic adipocytes performed in regulating glucose, the impaired capability of thermogenic fat tissue may give rise to metabolic disorders in vivo.…”
Section: The Developmental Origin and Anatomical Location Of Thermoge...mentioning
confidence: 99%
“…GE triggered glucose disposal into the iWAT and BAT but not eWAT and this tissue distribution pattern coincides with the occurrence of brown or beige/brite adipocytes in mice housed at room temperature (Waldén et al, 2012). Very recent data from female BAT-specific Rab10 knockdown mice supports the notion that catabolic adipocytes contribute to systemic glucose metabolism independent of their thermogenic role (Picatoste et al, 2021). Moreover, GE treatment was associated with a decreased eWAT to iWAT ratio indicating that more glucose is directed to the subcutaneous depot causing a shift in fat distribution.…”
Section: Discussionmentioning
confidence: 52%
“…The targets of TBC1D4 GAP activity are Rab2A, Rab8A, Rab10 and Rab14 ( Miinea et al, 2005 ). Knockdown of Rab10 in cultured mouse adipocytes and knockout of Rab10 in primary adipocytes (white and brown) reduce insulin-stimulated GLUT4 translocation, identifying Rab10 as a TBC1D4 target required for GLUT4 translocation in adipocytes ( Sano et al, 2007 ; Vazirani et al, 2016 ; Picatoste et al, 2021 ). TBC1D4 is also an AMPK target; therefore, we investigated whether Rab10 has a role in AMPK-induced translocation of GLUT4 in SKM-GLUT4 cells.…”
Section: Resultsmentioning
confidence: 99%