After absorption into intestinal epithelial cells, fatty acids can be stored in lipid droplets (LDs) in forms of triacylglycerol (TAG) and cholesterol esters (CE). Inefficient incorporation of fatty acids into TAG can induce lipotoxicity and kill cells. A core set of acyltransferases, localized on the endoplasmic reticulum (ER), are highly conserved enzymes for TAG synthesis in metazoans. Some acyltransferases showed clear preference for specific subgroup of fatty acids, in terms of chain length and degree of unsaturation. How they incorporate less favorable fatty acids into TAG remains unclear. Here, we report the identification of the conserved transmembrane protein TMEM-120 as a potential enhancer of TAG synthesis that overcomes substrate preference. Loss of TMEM-120 function retards...[ Read more ]

After absorption into intestinal epithelial cells, fatty acids can be stored in lipid droplets (LDs) in forms of triacylglycerol (TAG) and cholesterol esters (CE). Inefficient incorporation of fatty acids into TAG can induce lipotoxicity and kill cells. A core set of acyltransferases, localized on the endoplasmic reticulum (ER), are highly conserved enzymes for TAG synthesis in metazoans. Some acyltransferases showed clear preference for specific subgroup of fatty acids, in terms of chain length and degree of unsaturation. How they incorporate less favorable fatty acids into TAG remains unclear. Here, we report the identification of the conserved transmembrane protein TMEM-120 as a potential enhancer of TAG synthesis that overcomes substrate preference. Loss of TMEM-120 function retards TAG storage and LD expansion in C. elegans. Results from Stimulated Raman Scattering indicated that TMEM-120 deficiency reduced the rate of fatty acid accumulation, without affecting the rate of basal lipolysis. Morphometric measurement of LDs suggested that TMEM-120 plays a broad role of regulating dietary fatty acid incorporation into TAG. Lipidomic analysis further revealed that TMEM-120-deficienct worms are preferentially depleted of TAGs that harbor acyl chains shorter than 18 carbons. Functional GFP fusion proteins of TMEM-120, expressed at the endogenous level, are localized on the ER. Taken together, our studies revealed that, in contrast to its previously assigned role as a mechanosensory ion channel, TMEM-120 is localized on the ER, and promotes the incorporation of specific fatty acids into TAG.