Positive feedback leads to obesity — Lipid droplet formation triggers lipid synthesis and accumulation in adipocytes
July 1, 2013
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A positive feed-forward loop in the presence of perilipin: (1) lipid droplet formation, (2) SREBP-1 activation, (3) increased lipid synthesis, (4) stimulation of lipid droplet formation. © Ryuichiro Sato.
Excess accumulation of lipid droplets in adipose tissues leads to obesity. Although clarifying the molecular mechanism of lipid droplet formation is a critical issue to be addressed for preventing obesity, the precise mechanism remains unresolved. Adipose tissue is the only tissue in our body that functions as a reservoir of triacylglycerol, stored as an energy source. Perilipin, a protein found on the surface of lipid droplets, is synthesized only in adipocytes to protect this reservoir. Lipid droplets surrounded by perilipin are resistant to attack by lipases, and as a result get loaded with more lipids. It has been reported that adipocytes in perilipin-null mice (mice unable to produce perilipin) include small lipid droplets and that these mice are resistant to high fat diet-induced obesity. The current study by researchers at the University of Tokyo's Graduate School of Agricultural and Life Sciences revealed that SREBP-1, a transcription factor that facilitates lipogenic gene expression, was not sufficiently activated in adipose tissues in perilipin-null mice. This study demonstrated that there exists a positive feed-forward loop: lipid droplet formation leads to SREBP-1 activation, which in turn brings about an increase in lipid synthesis and thereby the stimulation of lipid droplet formation. Because reducing lipid droplet formation in adipocytes leads to obesity resistance, this study represents a new approach for reducing obesity by blocking the aforementioned loop.
Yu Takahashi, Akihiro Shinoda, Norihiko Furuya, Eri Harada, Naoto Arimura, Ikuyo Ichi, Yoko, Fujiwara, Jun Inoue, Ryuichiro Sato, "Perilipin-mediated lipid droplet formation in adipocytes promotes sterol regulatory element-binding protein-1 processing and triacylglyceride accumulation," PLoS ONE 8(5): e64605, doi: 10.1371/journal.pone.0064605.