Abstract
SummaryAs circulating lipid levels are balanced by the rate of lipoprotein release and clearance from the plasma, lipid absorption in the small intestine critically contributes to the maintenance of whole-body lipid homeostasis. Within enterocytes, excessive triglycerides are transiently stored as cytosolic lipid droplets (cLDs), and their mobilization sustains lipid supply during interprandial periods. Using mice lacking adipose triglyceride lipase (ATGL) and its coactivator comparative gene identification-58 (CGI-58) exclusively in the intestine (intestine-specific double KO [iDKO]), we show that ATGL/CGI-58 are not involved in providing substrates for chylomicron synthesis. Massive intestinal cLD accumulation in iDKO mice independent of dietary lipids together with inefficient lipid incorporation into cLDs in the early absorption phase demonstrate the existence of a secretion/re-uptake cycle, corroborating the availability of two diverse cLD pools. This study identified ATGL/CGI-58 as critical players in the catabolism of basolaterally (blood) derived lipids and highlights the necessity to modify the current model of intestinal lipid metabolism.
Highlights
Lipid metabolism comprises anabolic and catabolic processes, for which the small intestine (SI) plays a crucial role in maintaining systemic energy homeostasis
Intestinal adipose triglyceride lipase (ATGL) and comparative gene identification-58 (CGI-58) Do Not Provide Substrates for CM Synthesis With the exception of 32% decreased TG concentrations in iDKO mice fasted for 16 h, plasma lipid parameters were comparable between the genotypes mice under various dietary conditions (Table 1). These results indicate that ATGL/CGI-58 are not involved in the hydrolysis of dietary lipids to provide free fatty acids (FFAs) as substrates for CM synthesis
We have previously shown that FFAs released by ATGL-mediated TG hydrolysis in enterocytes function as signaling molecules and participate in PPARa activation within enterocytes (Obrowsky et al, 2013)
Summary
Lipid metabolism comprises anabolic (lipogenic) and catabolic (lipolytic) processes, for which the small intestine (SI) plays a crucial role in maintaining systemic energy homeostasis. Dietary lipids such as triglycerides (TGs), cholesteryl 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, 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). The SI participates in the control of blood lipid concentrations and the development of cardiovascular diseases (Simons et al, 1987)
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