Abstract
Adipose tissue stores neutral lipids and is a major metabolic organ involved in regulating whole-body energy homeostasis. Triacylglycerol is stored as unilocular large lipid droplets (LDs) in white adipocytes and as multilocular small LDs in brown adipocytes. Proteins of the cell death-inducing DNA fragmentation factor A-like effector (Cide) family include CideA, CideB, and fat-specific protein of 27 (FSP27). Of these, FSP27 has been shown to play a crucial role in the formation of unilocular large LDs in white adipocytes. However, the mechanisms by which brown adipocytes store small and multilocular LDs remain unclear. An FSP27 isoform, FSP27β, was recently identified. We herein report that CideA and FSP27β are mainly expressed in brown adipose tissue and that FSP27β overexpression inhibits CideA-induced LD enlargements in a dose-dependent manner in COS cells. Furthermore, RNAi-mediated FSP27β depletion resulted in enlarged LDs in HB2 adipocytes, which possess the characteristics of brown adipocytes. Brown adipocytes in FSP27-knock-out mice that express CideA, but not FSP27β, had larger and fewer LDs. Moreover, we confirmed that FSP27β and CideA form a complex in brown adipose tissue. Our results suggest that FSP27β negatively regulates CideA-promoted enlargement of LD size in brown adipocytes. FSP27β appears to be responsible for the formation of small and multilocular LDs in brown adipose tissue, a morphology facilitating free fatty acid transport to mitochondria adjacent to LDs for oxidation in brown adipocytes.
Highlights
Adipose tissue stores neutral lipids and is a major metabolic organ involved in regulating whole-body energy homeostasis
We confirmed that fat-specific protein of 27 (FSP27) and CideA form a complex in brown adipose tissue
These results were consistent with those obtained on mRNA expression and suggest that FSP27␣ is expressed in eWAT, whereas FSP27 and CideA are expressed in brown adipose tissue (BAT)
Summary
We initially investigated the mRNA expression of FSP27␣, FSP27, and CideA in the epididymal white adipose tissue. CREBH, cyclic-AMP-responsive element-binding protein H; BAT, brown adipose tissue; FFA, free fatty acid; (e)WAT, (epididymal) white adipose tissue; homo, homozygous; hetero, heterozygous
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