Abstract

Maintenance of energy homeostasis depends on the highly regulated storage and release of triacylglycerol primarily in adipose tissue, and excessive storage is a feature of common metabolic disorders. CIDEA is a lipid droplet (LD)-protein enriched in brown adipocytes promoting the enlargement of LDs, which are dynamic, ubiquitous organelles specialized for storing neutral lipids. We demonstrate an essential role in this process for an amphipathic helix in CIDEA, which facilitates embedding in the LD phospholipid monolayer and binds phosphatidic acid (PA). LD pairs are docked by CIDEA trans-complexes through contributions of the N-terminal domain and a C-terminal dimerization region. These complexes, enriched at the LD-LD contact site, interact with the cone-shaped phospholipid PA and likely increase phospholipid barrier permeability, promoting LD fusion by transference of lipids. This physiological process is essential in adipocyte differentiation as well as serving to facilitate the tight coupling of lipolysis and lipogenesis in activated brown fat.

Highlights

  • Evolutionary pressures for survival in fluctuating environments that expose organisms to times of both feast and famine have selected for the ability to efficiently store and release energy in the form of triacylglycerol (TAG)

  • As CIDEA is selectively expressed in brown adipocytes and could have a prominent role in the acquisition of their multilocular morphology, we explored the effects of its expression in undifferentiated pre-adipocytes

  • The Cidea gene is highly expressed in brown adipose tissue (BAT), induced in white adipose tissue (WAT) following cold exposure (Rosell et al, 2014), and is widely used by researchers as a defining marker to discriminate brown or brite adipocytes from white adipocytes (Harms and Seale, 2013; Zhou et al, 2003)

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Summary

Introduction

Evolutionary pressures for survival in fluctuating environments that expose organisms to times of both feast and famine have selected for the ability to efficiently store and release energy in the form of triacylglycerol (TAG). The organelles that are essential for storing and mobilizing intracellular fat are lipid droplets (LDs) (Walther and Farese, 2012). They constitute a unique cellular structure where a core of neutral lipids is stabilized in the hydrophilic cytosol by a phospholipid monolayer embedding LD proteins. While most mammalian cells present small LDs (

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