Significance was calculated by unpaired Students t test or ANOVA followed by Bonferroni post-tests. systemic energy homeostasis. After food intake, dietary lipids such as triglycerides (TGs), cholesteryl FR194738 esters (CEs), and phospholipids (PLs) are initially cleaved by oral and gastric hydrolases. The majority of luminal hydrolysis of TGs into free fatty acids (FFAs) and 2-monoacylglycerol is catalyzed by pancreatic lipase (PTL). These hydrolysis products are further emulsified with bile acids and packed into micelles in the lumen of the SI, FLJ45651 where they are taken up by the apical side of enterocytes, either via passive diffusion or by protein-mediated transport mechanisms (Poirier et al., 1996; Phan and Tso, 2001; Abumrad and Davidson, 2012; Iqbal and Hussain, 2009). Absorbed TG precursors are re-esterified in the endoplasmic reticulum and FR194738 either used for chylomicron (CM) synthesis or serve as a transient lipid storage pool in the form of cytosolic lipid droplets (cLDs). Together with very low density lipoproteins (VLDLs), CMs represent the main TG source for peripheral cells and tissues and are pivotal contributors to postprandial hypertriglyceridemia (Demignot et al., 2014). Therefore, the SI participates in the control of blood lipid concentrations and the development of cardiovascular diseases (Simons et al., 1987). Generally, cLDs are essential organelles for the prevention of lipotoxicity by re-esterification of FFAs into TGs (Schaffer, 2003). cLDs also serve as a reservoir for hydrophobic molecules with important biological functions including fat-soluble vitamins, prostaglandins, and steroids (Demignot et al., 2014). The current hypothesis states that intestinal cLDs optimize lipid absorption during food intake and provide sustained lipid supply during fasting (Beilstein et al., 2016). The gut is also able to take up FFAs from the circulation, derived from white adipose tissue (WAT) or vascular FR194738 lipolysis, hepatic-derived small lipoprotein particles, or CM remnants (Soued and Mansbach, 1996). Recent findings indicate the existence of two different TG pools in enterocytes, as evidenced by diverging fates of apically (diet) and basolaterally (circulation) derived lipids. Although lipids taken up via the apical brush border membrane are mainly incorporated into TGs and directed toward the secretory pathway, basolateral lipids are destined FR194738 for fatty acid (FA) -oxidation or phospholipid (PL) synthesis (Storch et al., 2008; Ho et al., 2002; Gangl and Ockner, 1975). This might be due to different compartmentation of intracellular organelles, as mitochondria are dispersed throughout the enterocyte but predominate at the basal pole, while the endoplasmic reticulum is concentrated rather on the apical side of the cell (Gangl and Ockner, 1975). In humans, sequential meal studies described the existence of transient intestinal lipid storage pools, as TGs stored in cLDs showed the same FA composition as TGs ingested with the previous meal (Fielding et al., 1996; Evans et FR194738 al., 1998; Jackson et al., 2002). In mice, the number and size of cLDs increase during dietary fat absorption with a maximum 3 h post-gavage and an almost complete depletion 12 h after digestion (Zhu et al., 2009). Lipolysis is necessary to mobilize stored lipids, which are further used for energy production and membrane biosynthesis (Farese and Walther, 2009) or serve as ligands for transcription factors (Zechner et al., 2012). In WAT, lipolysis of TGs stored in cLDs has already been well described, and adipose TG lipase (ATGL) together with its coactivator comparative gene identification-58 (CGI-58) mediates the initial step of TG hydrolysis (Zimmermann et al., 2004; Yen and Farese, 2006; Lass et al., 2006). However, the mechanisms accountable for the breakdown of cLDs in the SI are still elusive. We hypothesized that the enzymatic pathway responsible for the degradation of intestinal cLDs involves CGI-58 and ATGL. Our previous research suggested.