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  • Title: VLDL-VLDLR axis facilitates brown fat thermogenesis through replenishment of lipid fuels and PPARβ/δ activation.
    Author: Shin KC, Huh JY, Ji Y, Han JS, Han SM, Park J, Nahmgoong H, Lee WT, Jeon YG, Kim B, Park C, Kang H, Choe SS, Kim JB.
    Journal: Cell Rep; 2022 Dec 13; 41(11):111806. PubMed ID: 36516764.
    Abstract:
    In mammals, brown adipose tissue (BAT) is specialized to conduct non-shivering thermogenesis for survival under cold acclimation. Although emerging evidence suggests that lipid metabolites are essential for heat generation in cold-activated BAT, the underlying mechanisms of lipid uptake in BAT have not been thoroughly understood. Here, we show that very-low-density lipoprotein (VLDL) uptaken by VLDL receptor (VLDLR) plays important roles in thermogenic execution in BAT. Compared with wild-type mice, VLDLR knockout mice exhibit impaired thermogenic features. Mechanistically, VLDLR-mediated VLDL uptake provides energy sources for mitochondrial oxidation via lysosomal processing, subsequently enhancing thermogenic activity in brown adipocytes. Moreover, the VLDL-VLDLR axis potentiates peroxisome proliferator activated receptor (PPAR)β/δ activity with thermogenic gene expression in BAT. Accordingly, VLDL-induced thermogenic capacity is attenuated in brown-adipocyte-specific PPARβ/δ knockout mice. Collectively, these data suggest that the VLDL-VLDLR axis in brown adipocytes is a key factor for thermogenic execution during cold exposure.
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