CIDE Family-Mediated Unique Lipid Droplet Morphology in White Adipose Tissue and Brown Adipose Tissue Determines the Adipocyte Energy Metabolism

Abstract

White adipose tissue (WAT) stores energy as triacylglycerol in preparation for fasting state. In contrast, brown adipose tissue (BAT) consumes energy and produces heat in a cold environment. One of the major differences between these two adipose tissues is the morphology of the intracellular lipid droplet (LD), which is large and unilocular in WAT and small and multilocular in BAT. Although the fat-specific protein 27 alpha (FSP27α), belonging to the cell death-inducing DNA fragmentation factor A (DFFA)-like effector (Cide) family, was known to be indispensable for large unilocular LD formation in WAT, the mechanism that regulated small multilocular LD formation in BAT remained unknown. We recently uncovered that FSP27β, a novel isoform of FSP27 abundantly expressed in BAT, plays a crucial role in small multilocular LD formation by inhibiting the homodimerization of CideA in BAT. We speculate that unilocular LD formation is ideal for efficient lipid storage in WAT because lipolysis from the LD surface is restricted due to the minimum LD surface area. In addition, hydrolyzed free fatty acid (FFA) and glycerol can efficiently flow out into the circulation from the cell surface. In contrast, small multilocular LD formation is ideal for efficient intracellular lipolysis from the LD surface and the subsequent facilitation of FFA transport to mitochondria that are adjacent to LDs for β-oxidation in BAT. Thus, intracellular LD morphology is closely related to the functions and characteristics of adipose tissues. Given that the browning of adipose tissue leads to enhanced energy expenditure and the prevention of obesity, clarification of the mechanism with respect to intracellular LD formation is very meaningful.

Lyophilized Maqui (Aristotelia chilensis) Berry Induces Browning in the Subcutaneous White Adipose Tissue and Ameliorates the Insulin Resistance in High Fat Diet-Induced Obese Mice

“…Fsp27a is expressed in WAT, where it promotes the formation of large LDs. By contrast, BAT expresses the Fsp27b isoform that contributes to the ensemble of smaller LDs [53,54]. To confirm the brown-like phenotype of scWAT in HFDM mice, the mRNA levels of both Fsp27 isoforms were measured.…”

Black Raspberry (Rubus coreanus Miquel) Promotes Browning of Preadipocytes and Inguinal White Adipose Tissue in Cold-Induced Mice

“…As shown in Figure 3G, a Mitotracker staining assay revealed increased abundancy of mitochondria in BRWE-treated cells. Increased factors of mitochondrial abundance and action including cell death activator (CIDEA) [24] and nuclear respiratory factor 1 (NRF1) [25] showed the increased mitochondrial biogenesis/activation induced by BRWE, and furthermore, the increased mitochondria enzyme carnitine palmitoyltransferase 1B (CPT1B) [26] indicated increased mitochondrial β-oxidation by BRWE treatment (Figure 3H).…”

An Ancient Chinese Herbal Decoction Containing Angelicae Sinensis Radix, Astragali Radix, Jujuba Fructus, and Zingiberis Rhizoma Recens Stimulates the Browning Conversion of White Adipocyte in Cultured 3T3-L1 Cells

“…The major functions of WAT are heating insulation, buffering mechanical cushion, and, finally, storing of energy. WAT is acting as fuel for energy imbalances when the intaking energy is smaller than outputting energy; therefore, WAT is considered as a crucial component in contributing obesity [6]. BAT, on the other hand, accelerates energy expenditure and finally combats obesity [7, 8].…”