Lipid Droplets in Cancer: Guardians of Fat in a Stressful World

This is a very interesting paper reviewing the role of lipid droplets.

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Figure 4. Autophagy and phospholipase-mediated phospholipid hydrolysis stimulate lipid droplet biogenesis during stress. Nutrient starvation activates the autophagy-mediated breakdown of membranous organelles leading to the release of various saturated and unsaturated fatty acids (FAs) that drive diacylglycerol acyltransferase 1 (DGAT1)-mediated lipid droplet biogenesis. Cellular stress may also lead to phospholipase A₂ (PLA₂) activation and membrane phospholipid hydrolysis that predominantly results in the release of unsaturated and polyunsaturated fatty acids (FAs), which are typically found at the sn-2 position of membrane phospholipids. Intracellular phospholipases A₂, such as the calcium-independent group VIA PLA₂ (iPLA₂β or PNPLA9), or secreted isoforms, such as the group X secreted PLA₂, may drive lipid droplet biogenesis. Oxidative stress may lead to phospholipase D (PLD)-mediated redistribution of FAs from membrane phospholipids to triacylglycerols (TAGs) stored within lipid droplets in order to protect polyunsaturated FAs from peroxidation. Phospholipase D (PLD) converts phosphatidylcholine (PC) to phosphatidic acid (PA), whereas phosphatidate phosphatases (lipins) convert PA to diacylglycerol (DAG). The latter is then available for TAG synthesis by DGAT1 or DGAT2. Phospholipase activity-derived FAs could be preferred when a specific phospholipid and/or TAG acyl-chain remodelling is required instead of the bulk FA mixture provided by autophagy. Future studies will provide clues on the possible crosstalk between these pathways and the conditions that govern the predominant mechanisms of lipid droplet biogenesis during various conditions of stress in different cell types.

Abstract

Cancer cells possess remarkable abilities to adapt to adverse environmental conditions. Their survival during severe nutrient and oxidative stress depends on their capacity to acquire extracellular lipids and the plasticity of their mechanisms for intracellular lipid synthesis, mobilisation, and recycling. Lipid droplets, cytosolic fat storage organelles present in most cells from yeast to men, are emerging as major regulators of lipid metabolism, trafficking, and signalling in various cells and tissues exposed to stress. Their biogenesis is induced by nutrient and oxidative stress and they accumulate in various cancers. Lipid droplets act as switches that coordinate lipid trafficking and consumption for different purposes in the cell, such as energy production, protection against oxidative stress or membrane biogenesis during rapid cell growth. They sequester toxic lipids, such as fatty acids, cholesterol and ceramides, thereby preventing lipotoxic cell damage and engage in a complex relationship with autophagy. Here, we focus on the emerging mechanisms of stress-induced lipid droplet biogenesis; their roles during nutrient, lipotoxic, and oxidative stress; and the relationship between lipid droplets and autophagy. The recently discovered principles of lipid droplet biology can improve our understanding of the mechanisms that govern cancer cell adaptability and resilience to stress. View Full-Text

Keywords: lipid droplets; fatty acids; autophagy; lipophagy; cancer; oxidative stress; nutrient stress; lipotoxicity; lipase; phospholipase

 

 

Biosynthesis of n-3 fatty acids in Nile tilapia

 

n-3 essential fatty acids in Nile tilapia, Oreochromis niloticus: Bioconverting LNA to DHA is relatively efficient and the LC-PUFA biosynthetic pathway is substrate limited in juvenile fish

This paper is an excellent study on the biosynthesis of n-3 fatty acids  inn Nile tilapia and gives us some insight how we could enhance this anabolism of fatty acids with the view to improve cardioprotective properties.